Abstract
PURPOSE
In immunoglobulin light chain (AL) amyloidosis, amyloid fibrils cause organ dysfunction. Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance.
METHODS
Newly diagnosed patients with European modification of Mayo 2004 stage IIIa or IIIb AL amyloidosis were randomly assigned to receive anselamimab or placebo with cyclophosphamide, bortezomib, and dexamethasone (with or without daratumumab). The primary end point was a hierarchical composite of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVHs), analyzed using the Finkelstein-Schoenfeld test and win ratio estimation.
RESULTS
Among 406 randomly assigned patients, the primary end point win ratio for anselamimab versus placebo was 1.11 (95% CI, 0.83, 1.50; P = .332) and the hazard ratio (HR) for ACM was 0.80 (95% CI, 0.57, 1.13; P = .290). CVH rates in the anselamimab and placebo groups were 0.59 (95% CI, 0.42, 0.83) and 0.89 (95% CI, 0.55, 1.43), respectively (P = .145). Among patients with kappa isotype (n = 72), the win ratio was 2.06 (95% CI, 0.98, 4.31; P = .100) and anselamimab reduced ACM by 62% versus placebo (HR, 0.38; 95% CI, 0.17 to 0.86; nominal P = .012), and CVH by 71% (IRR, 0.29; 95% CI, 0.10 to 0.87; nominal P = .028) with improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score. There was no clinical benefit observed in the lambda population. Anselamimab was generally well-tolerated; safety data were comparable between treatment arms overall.
CONCLUSION
Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype.
INTRODUCTION
Light chain (AL) amyloidosis is a rare, life-threatening disease caused by plasma cell dyscrasia (PCD) producing excess free, unstable immunoglobulin light chains.1-3 Misfolded free light chains are cytotoxic and aggregate into fibrils that deposit in target organs, notably in the heart and kidneys.1,2,4 The disease is rapidly progressive, with high early mortality when diagnosed in advanced stages.5-7 Cardiac involvement, the primary determinant of prognosis staged by serum biomarkers of myocardial injury, is common.8,9 Approximately 79% and 21% of patients with AL amyloidosis have lambda and kappa light chain isotypes, respectively.10-12 The organ tropism and impact of the light chain isotype on clinical presentation is variable.13-15
CONTEXT
Key Objective
To determine the safety and efficacy of anselamimab in addition to standard of care in patients with advanced cardiac light chain (AL) amyloidosis.
Knowledge Generated
Anselamimab improves survival in patients with kappa isotype AL amyloidosis and was well-tolerated. Anselamimab also reduces cardiovascular hospitalizations.
Relevance (J.W. Friedberg)
Although this study was negative for its primary endpoint, the efficacy signal in kappa isotype AL amyloidosis was strong and has biological plausibility. Future trials restricting enrollment to this subset of patients should be performed to validate this finding.*
*Relevance section written by JCO Editor-in-Chief Jonathan W. Friedberg, MD.
Anselamimab (originally CAEL101) is a chimeric immunoglobulin (Ig)G1 kappa monoclonal antibody (mAb) directed against human kappa light chain fibril and has shown preclinical reactivity against both isotypes.16-19 Anselamimab reacts with specificity in a conformation-dependent manner with unique epitopes on amyloid fibrils and amyloidogenic light chain aggregates, but not with nonamyloid or circulating free light chains.16 In a mouse model, anselamimab facilitated regression of amyloidomas by eliciting an immune response that facilitates elimination of prefibrillar aggregates in circulation and amyloid fibrils deposited in organs.16,18,19 Phase I and II clinical trials demonstrated that anselamimab was well-tolerated either as monotherapy or in combination with anti-PCD treatment, including daratumumab and cyclophosphamide, bortezomib, and dexamethasone (CyBorD).20-24
Current treatments for AL amyloidosis, including chemotherapy, targeted immunotherapy, and autologous stem cell transplantation, suppress the underlying plasma cell clone but do not directly accelerate amyloid fibril clearance.1,25 The involved light chain isotype does not influence the choice of anti-PCD treatment regimen. Although the standard first-line regimen of daratumumab and CyBorD induces a high hematologic response, treatment response by the light chain isotype has not been reported in prospective trials.5,6,11
Despite advances seen with these therapies, early mortality stemming from cardiac events remains unchanged among patients with advanced disease in reports on prospective trials although retrospective analyses have shown benefits of early intervention with daratumumab.26-28 Long-term organ dysfunction remains a major cause of decreased quality of life.11 Hence, targeted therapy for amyloid fibril removal is a critical unmet need.1
Cardiac Amyloid Reaching for Extended Survival (CARES) was designed to determine the efficacy and safety of anselamimab in combination with standard of care (SoC) anti-PCD therapy in patients with European modification of Mayo 2004 stage IIIa and IIIb kappa and lambda AL amyloidosis.
METHODS
Study Design and Oversight
The CARES program included two parallel, multicenter, international, double-blind, placebo-controlled phase III trials in patients with European modification of Mayo 2004 stage IIIa (CAEL101-302; ClinicalTrials.gov identifier: NCT04512235) and stage IIIb (CAEL101-301; ClinicalTrials.gov identifier: NCT04504825) AL amyloidosis (Data Supplement, Fig S1, online only). CARES enrolled patients from 19 countries and was approved by the independent review board or ethics committee at each site, in accordance with the provisions of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines. Eligible patients provided written informed consent and were randomly assigned using a centralized interactive response technology and stratified by geographic region. An external data and safety monitoring board monitored patient safety and conducted unblinded reviews of cumulative trial data. An independent adjudication committee determined whether investigator-reported events met the definition of unplanned cardiovascular hospitalizations (CVHs) with the use of predefined end point criteria in a blinded manner. The statistical analysis was performed by the sponsor, and data tables were provided to the investigators. All authors participated in the data interpretation and review of the manuscript and vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol, which is available with the full text of this article.
Patients and Interventions
Both studies enrolled treatment-naïve adult patients diagnosed with either Mayo stage IIIb (N-terminal probrain natriuretic peptide [NT-proBNP] >8,500 ng/L; ClinicalTrials.gov identifier: NCT04504825) or IIIa (NT-proBNP ≥650 and ≤8,500 ng/L; ClinicalTrials.gov identifier: NCT04512235) AL amyloidosis.
Eligible patients were randomly assigned 2:1 to receive anselamimab (1,000 mg/m2) or placebo intravenously, in addition to planned anti-PCD treatment with CyBorD according to the institutional SoC. Daratumumab was permitted where available but was not required. Patients received anselamimab or placebo once every 7 (±1) days for the first four infusions and then once every 14 (±2) days for the duration of the primary evaluation treatment period (PETP). The primary analysis was conducted 18 months after the last patient was enrolled in each trial (Data Supplement, Fig S1). Data collected separately from each trial were pooled for the primary analysis.
End Points
The original trial design was based on a primary end point of time to all-cause mortality (ACM) and was intended to continue until a prespecified number of mortality events. During the conduct of the trials, it became clear that the number of prespecified mortality events would not be reached in a reasonable time because of marked improvements in anti-PCD therapy. Therefore, the protocols were amended so that the primary analysis would be conducted 18 months after the last patient was randomly assigned, regardless of the number of deaths observed. The primary end point was also revised to a hierarchical combination of time to ACM and morbidity, expressed as frequency of CVH, defined as because of arrhythmia, heart failure, stroke, myocardial infarction, or unstable angina. Adjudication was conducted by an independent panel of experts who had no other relationship to these trials and were blinded to the randomized treatment assignment.
The components of the composite end point, time to ACM and frequency of CVH, were each analyzed separately as key secondary end points. Additional key secondary end points were changes from baseline (CFB) to week 50 in Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS), the 6-minute walk test (6MWT), and echocardiographic global longitudinal strain (GLS%). As there could be differential effects on kappa and lambda amyloid fibrils, a prespecified analysis of the primary and secondary end points by the light chain isotype, kappa or lambda, was conducted. Adverse events were tabulated for all patients receiving at least one dose of intervention according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.29
Statistical Analysis
The sample size estimated for time to ACM was 124 and 267 patients for CAEL101-301 and CAEL101-302, respectively. Improvements in SoC since these trials were initiated prompted a study amendment. The primary end point was changed to a hierarchical composite end point, and the analysis plan was revised to pool the studies. Simulations assuming a 50% relative reduction in the risk of death and CVH frequency yielded a power of >85% for the revised plan. Analysis for the primary end point was conducted on the pooled intent-to-treat (ITT) population from both studies using the stratified Finkelstein-Schoenfeld (F-S) test and win ratio estimation, with strata determined by trial, geographic region (North American or rest of the world), and daratumumab use at baseline.30,31 Within each stratum, all patient pairs were compared first on time to ACM and, if a winner could not be identified, then patients were compared on CVH frequency for the F-S test. The win ratio estimate is the number of pairs of treated patient wins divided by the number of pairs of placebo patient wins. Time to ACM was tested using the stratified log-rank test, and hazard ratio (HR) was estimated using the Cox proportional hazards model. CVH frequency was analyzed using negative binomial regression. All other secondary end points were analyzed using ranked analysis of covariance. The key secondary end points were tested for nominal significance: CFB to week 50 in KCCQ-OS and the 6MWT, time to ACM from random assignment to end of PETP, frequency of CVH from random assignment to the end of PETP, and CFB to week 50 in GLS%. For hematologic response, difference (95% CI) between anselamimab and placebo in proportion of patients was estimated using a stratified Cochran-Mantel-Haenszel method.
RESULTS
Patients
A total of 406 newly diagnosed patients were randomly assigned, of whom 72 (17.7%) had the kappa isotype. The demographics and disease characteristics at baseline were balanced between the groups in the overall population (Table 1 and Data Supplement, Table S1). However, some disease characteristics were slightly different between the overall population and the kappa isotype population. The median difference between involved and uninvolved free light chains (dFLC) was 310 mg/L (range, 4-10,057 mg/L) in the overall population and 483 mg/L (range, 4-4,668 mg/L) in the kappa isotype group. Among the 406 patients, 61.8% and 33.3% were classified as Mayo stage IIIa and IIIb, respectively, and 54.2% and 41.7% of kappa isotype patients were in Mayo stage IIIa and IIIb, respectively. In addition, among the kappa isotype population receiving anselamimab, there were more patients in stage IIIb (n = 23; 47.9%) with higher median NT-proBNP levels (8,215.1 ng/L) but lower median dFLC levels (385 mg/L) than those receiving placebo (corresponding values: n = 7 [29.2%]; 5,456.0 ng/L; 514 mg/L; Table 1).
TABLE 1.
Baseline Demographics and Disease Characteristics (intent-to-treat population)
| Characteristic | Overall Population | Kappa Isotype | ||
|---|---|---|---|---|
| Anselamimab (n = 271) | Placebo (n = 135) | Anselamimab (n = 48) | Placebo (n = 24) | |
| Age, years, median (range) | 66 (36-91) | 69 (36-90) | 68 (44-83) | 70 (52-85) |
| Distribution, years, No. (%) | ||||
| <65 | 118 (43.5) | 47 (34.8) | 18 (37.5) | 6 (25.0) |
| ≥65 | 153 (56.5) | 88 (65.2) | 30 (62.5) | 18 (75.0) |
| Sex, No. (%) | ||||
| Male | 183 (67.5) | 88 (65.2) | 37 (77.1) | 18 (75.0) |
| Female | 88 (32.5) | 47 (34.8) | 11 (22.9) | 6 (25.0) |
| Race or ethnic group, No. (%) | ||||
| White | 183 (67.5) | 93 (68.9) | 34 (70.8) | 18 (75.0) |
| Asian | 43 (15.9) | 14 (10.4) | 10 (20.8) | 1 (4.2) |
| Black | 13 (4.8) | 7 (5.2) | 3 (6.3) | 1 (4.2) |
| Other | 32 (11.8) | 21 (15.6) | 1 (2.1) | 4 (16.7) |
| Involved FLC isotype, No. (%) | ||||
| Kappa | 48 (17.7) | 24 (17.8) | ||
| Lambda | 219 (80.8) | 109 (80.7) | ||
| Missing | 4 (1.5) | 2 (1.5) | ||
| dFLC, mg/L, median (range) | 313 (11-10,057) | 299 (4-3,651) | 385 (11-4,668) | 514 (4-3,651) |
| NT-proBNP, ng/L, median (range) | 5,458.0 (784-49,896) | 5,318.6 (742-49,896) | 8,215.1 (784-49,896) | 5,456.0 (742-35,418) |
| Daratumumab use, No. (%) | ||||
| At any time | 215 (79.3) | 113 (83.7) | 35 (72.9) | 18 (75.0) |
| At baseline | 155 (57.2) | 85 (63.0) | 25 (52.1) | 12 (50.0) |
| Later | 60 (22.1) | 28 (20.7) | 10 (20.8) | 6 (25.0) |
Abbreviations: dFLC, difference between involved and uninvolved free light chains; FLC, free light chain; NT-proBNP, N-terminal probrain natriuretic peptide.
Patient Disposition
Of the 406 randomly assigned patients, 271 received at least one dose of anselamimab and 134 received at least one dose of placebo (Fig 1). By the end of the PETP (18 months after the last patient was enrolled), 143 (52.8%) patients in the anselamimab group and 76 (56.3%) patients in the placebo group had discontinued the intervention, most commonly because of death (Fig 1).
FIG 1.
Patient disposition (CONSORT). Flow diagram of the progress through the phases of a randomized trial of two groups, including enrollment, intervention allocation, follow-up, and data analysis. ITT, intent to treat; LVAD, left ventricular assist device.
Patients received anselamimab or placebo for a median of 21.4 months and 21.1 months, respectively. Among patients with the kappa isotype, the median duration of treatment was 22.3 months in the anselamimab group and 11.8 months in the placebo group. Daratumumab was used in 215 (79.3%) and 113 (83.7%) patients at any time during the PETP in the anselamimab and placebo groups, respectively. In the kappa isotype group, 35 (72.9%) and 18 (75.0%) patients received daratumumab at any time during PETP in the anselamimab and placebo groups, respectively.
Efficacy
In the primary analysis that hierarchically assessed ACM, followed by frequency of CVH, treatment with anselamimab was not associated with a statistically significant benefit compared with placebo by the F-S method, with a win ratio of 1.11 (95% CI, 0.83 to 1.50; P = .332; Table 2, Fig 2A). There were no significant differences between anselamimab and placebo in any of the secondary end points. In the prespecified isotype analyses, there was a notable difference between the kappa and lambda isotype populations in the primary end point (Fig 3A). CVH by category is reported in the Data Supplement (Table S2).
TABLE 2.
Summary of Primary Efficacy End Points
| End Point | Overall Population | Kappa Isotype | Lambda Isotype | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Anselamimab (n = 271) | Placebo (n = 135) | P | Anselamimab (n = 48) | Placebo (n = 24) | P | Anselamimab (n = 219) | Placebo (n = 109) | P | |
| ACMa and CVH win ratio (95% CI) | 1.11 (0.83 to 1.50) | .332 | 2.06 (0.98 to 4.31) | .100 | 0.90 (0.64 to 1.27) | .848 | |||
| ACM | |||||||||
| No. (%) | 90 (33.2) | 52 (38.5) | 15 (31.3) | 14 (58.3) | 73 (33.3) | 37 (33.9) | |||
| Hazard ratio (95% CI)b | 0.80 (0.57 to 1.13) | .290 | 0.38 (0.17 to 0.86) | .012 | 1.02 (0.68 to 1.52) | .647 | |||
| CVH | |||||||||
| Frequency per year (95% CI)c | 0.59 (0.42 to 0.83) | 0.89 (0.55 to 1.43) | 0.41 (0.20 to 0.83) | 1.40 (0.58 to 3.36) | 0.66 (0.44 to 0.98) | 0.76 (0.43 to 1.34) | |||
| Incidence risk ratio (95% CI)c | 0.67 (0.39 to 1.15) | .145 | 0.29 (0.10 to 0.87) | .028 | 0.87 (0.46 to 1.65) | .664 | |||
NOTE. The primary efficacy end point was evaluated 18 months after the last patient was enrolled in each study. P value is calculated using the stratified Finkelstein-Schoenfeld test, and the treatment effect was estimated using the win ratio method.
Abbreviations: ACM, all-cause mortality; CVH, cardiovascular hospitalization.
Heart transplant/left ventricular assist device implantation is treated as ACM.
The HR (95% CI) for anselamimab versus placebo is obtained using a Cox proportional hazards model. P value is obtained using the stratified log-rank test.
Frequency of CVH (95% CI), incidence risk ratio (95% CI), and P value are obtained using a negative binomial regression analysis.
FIG 2.
Kaplan-Meier analysis of time to ACM in the (A) overall population, (B) patients with the kappa isotype, and (C) patients with the lambda isotype. Censor events are shown by vertical tick marks. ACM, all-cause mortality; PCD, plasma cell dyscrasia.
FIG 3.
Forest plot by subgroups of the primary end point in (A) the overall population and (B) select subgroups in patients with the kappa isotype. FLC, free light chain; GLS%, global longitudinal strain; ID, identifier; NYHA, New York Heart Association; PCD, plasma cell dyscrasia.
In the kappa isotype population, the estimated win ratio for the primary end point between the anselamimab and placebo groups was 2.06 (95% CI, 0.98 to 4.31, nominal P = .100; Table 2). The corresponding win ratio for patients with the lambda isotype was 0.90 (95% CI, 0.64 to 1.27, nominal P = .848; Table 2). In addition, in the kappa isotype population, there was significant and clinically meaningful reduction in incidence of ACM (62% reduction; HR, 0.38 [95% CI, 0.17 to 0.86]; nominal P = .012) and frequency of CVH (71% decrease; estimated CVH rate ratio of 0.29 [95% CI, 0.10 to 0.87]; nominal P = .028) with anselamimab treatment versus placebo (Table 2, Fig 2B). In the lambda isotype population, there was no change in ACM (HR, 1.02 [95% CI, 0.68 to 1.52], P = .647) or CVH (rate ratio, 0.87 [95% CI, 0.46 to 1.65]; P = .664) versus placebo (Table 2, Fig 2C).
In the kappa isotype population, reductions by disease stage in ACM of 75% (HR, 0.25 [95% CI, 0.06 to 0.93]; nominal P = .021) and 48% (HR, 0.52 [95% CI, 0.17 to 1.54]; nominal P = .238) were observed among patients in Mayo stages IIIa (Fig 4A) and IIIb (Fig 4B), respectively. In addition, decreases in frequency of CVH of 48% (estimated rate ratio, 0.52 [95% CI, 0.09 to 3.14]; nominal P = .479) and 86% (estimated rate ratio, 0.14 [95% CI, 0.04 to 0.50]; nominal P = .003) were observed among patients in Mayo stages IIIa and IIIb, respectively. Trends favoring anselamimab for the primary end point were observed in all subgroups (≥15 patients) in the kappa isotype population (Fig 3B).
FIG 4.
Kaplan-Meier analysis of time to ACM in patients with the kappa isotype diagnosed with (A) Mayo stage IIIa and (B) Mayo stage IIIb. Censor events are shown by vertical tick marks. ACM, all-cause mortality; PCD, plasma cell dyscrasia.
In the kappa isotype population, an estimated median improvement of 10.37 points (95% CI, –9.38 to 26.56) was observed in KCCQ-OS at week 50 between the anselamimab and placebo groups, with improvements of 8.07 points (95% CI, –15.10 to 26.83) among patients in stage IIIa and 24.22 points (95% CI, –35.16 to 50.52) among patients in stage IIIb. There was no improvement observed in the lambda isotype population (Data Supplement, Table S3). In the kappa isotype population, there was also a favorable trend for anselamimab compared with placebo in 6MWT change at week 50 of 18.00 m (95% CI, –71.60 to 95.92 m). No differences between anselamimab and placebo were observed in GLS% for either light chain isotype at week 50.
Hematologic Response
There was no meaningful difference in hematologic response between the anselamimab and placebo groups in the overall ITT population or the kappa isotype population during PETP (Data Supplement, Table S4).
Safety
Safety data were comparable between the anselamimab and placebo groups in the overall PETP population (Table 3). The most frequently reported treatment-emergent adverse events (TEAEs) in ≥25% of patients in either arm were diarrhea, edema peripheral, constipation, nausea, COVID-19 disease, hypotension, cough, and fatigue (Data Supplement, Table S5). In anselamimab-treated patients, safety data in the kappa isotype population were generally consistent with those observed in the overall population (Table 3 and Data Supplement, Table S6).
TABLE 3.
Summary of Treatment-Emergent Adverse Events (safety population)
| Descriptiona | Anselamimab (n = 271), No. (%) | Placebo (n = 134), No. (%) |
|---|---|---|
| Any AE | 271 (100) | 134 (100) |
| Any SAE | 205 (75.6) | 101 (75.4) |
| AE leading to death | 75 (27.7) | 41 (30.6) |
| AE leading to discontinuation of study intervention | 36 (13.3) | 14 (10.4) |
| AE by intensity/gradeb | ||
| Grade 1 | 245 (90.4) | 124 (92.5) |
| Grade 2 | 253 (93.4) | 124 (92.5) |
| Grade 3 | 193 (71.2) | 102 (76.1) |
| Grade 4 | 62 (22.9) | 30 (22.4) |
| Grade 5 | 75 (27.7) | 41 (30.6) |
| At least AE grade 3 or higher | 218 (80.4) | 113 (84.3) |
NOTE. Treatment-emergent AEs are any AEs that begin between the start of the first infusion of study intervention and up to 140 days after the last study intervention date.
Abbreviations: AE, adverse event; SAE, serious adverse event.
Patients are counted once in each severity or relationship category in the case of multiple events.
Severity is assessed by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.29
DISCUSSION
Treatment with anselamimab in addition to SoC anti-PCD therapy did not demonstrate significant improvement in the hierarchical primary end point in overall population or kappa isotype patients. However, in patients with newly diagnosed kappa isotype AL amyloidosis treated in the CARES trials, anselamimab in combination with SoC demonstrated reductions in ACM and CVH and improvement in KCCQ-OS compared with placebo. There was no impact of anselamimab on patients with the lambda isotype. The estimated win ratio of composite end point in the kappa isotype population of 2.06 indicated that anselamimab-treated patients were twice as likely as placebo-treated patients to have better survival or fewer CVH. When the kappa isotype population was analyzed separately, compared with placebo, anselamimab demonstrated significant reductions in ACM among patients in Mayo stage IIIa and in CVH among patients in Mayo stage IIIb. These data may reflect that anselamimab was generated using a kappa isotype immunogen, and preclinical studies have indicated differences in affinity and binding to kappa amyloid fibrils versus lambda fibrils.16,18,19 This suggests that stronger binding to amyloid fibrils may lead to better amyloid clearance, a concept that needs further testing and evaluation.16,32 The lack of significance in the F-S test for the kappa isotype patients could be attributed to two main factors: (a) the kappa isotype population included only 72 patients, a small sample size for which the stratified F-S test is not suited, and (b) since the composite end point was hierarchical requiring evaluation of ACM first and CVH only in patients who were alive, a potential survivor bias complicated the CVH comparison. Although benefits on CVH were observed in patients who subsequently died, they did not contribute to the F-S test since CVH was only compared in patients who survived (tied in the ACM comparison). There was no additional benefit observed in patients who survived.
As expected, hematologic responses, based on reduction of dFLC in response to anti-PCD therapy, were comparable in both arms. The protocol allowed change in therapy per individual institution guidelines to achieve a favorable hematologic response. Since anselamimab targets removal of existing fibrils and not the production of new amyloidogenic light chains, it acts in a complementary manner with anti-PCD therapies. In this study, NT-proBNP decreased from baseline in the anselamimab treatment arm and the placebo arm for patients with either kappa or lambda isotype. The CFB to week 50 was greater in patients with the kappa isotype treated with anselamimab than those receiving placebo, but the difference was not nominally significant.
In the kappa isotype population, compared with placebo, anselamimab-treated patients showed improvements in KCCQ-OS substantially greater than the minimally clinically important difference (MCID), suggesting functional benefit from the treatment. Improvement was also observed for the 6MWT although it was not greater than MCID.33
There are no treatments available to eliminate amyloid fibrils already deposited in organs.1 The simplicity of identifying patients who may benefit from anselamimab is that a patient's light chain isotype is easily identified using standard tests for diagnosing AL amyloidosis.1,3,8 The clinical benefit of anselamimab in patients with kappa isotype AL amyloidosis, demonstrated independently in both CARES trials, suggests that anselamimab is a first-in-class, promising treatment that complements anti-PCD therapies. Anselamimab represents a major advancement in the treatment of AL amyloidosis by directly targeting amyloid fibrils, thereby improving survival beyond what is achievable with anti-PCD therapies alone.
The hypothesis for the development of antifibril mAb was that they would decrease light chain amyloid burden, irrespective of the isotype. However, our findings indicate that antifibril mAbs recognize highly discrete molecular epitopes and that earlier pan-amyloid strategies might have been based on an overly broad premise. This reason, along with a different mAb target and patient population, might have contributed to the different outcomes reported with other antifibril therapies.34-36
Because of the original design of the CARES trials, the size of the enrolled kappa population is a limitation. The kappa isotype represented 17.7% of the enrolled trial population, consistent with its reported prevalence. Kappa AL amyloidosis is considered ultrarare based on its epidemiology.37 The trials reported here represent the largest kappa AL amyloidosis population ever studied and include stage IIIb, which has been excluded from other clinical trials.
Anselamimab was generally well-tolerated when administered in combination with SoC treatment for PCD. Most of the commonly reported TEAEs are anticipated to occur with underlying AL amyloidosis, common comorbidities, and/or concomitant anti-PCD therapy use.
Anselamimab, a new kappa light chain–directed antifibril mAb used alongside anti-PCD therapy, may offer a fundamentally new therapeutic option for patients with newly diagnosed kappa AL amyloidosis.
ACKNOWLEDGMENT
Medical writing support was provided by Mukund Nori, PhD, MBA, CMPP, of rareLife solutions, Westport, CT, and funded by Alexion, AstraZeneca Rare Disease. A list of all the principal investigators who participated in at least one trial can be found in Appendix Table A1 (online only).
APPENDIX
TABLE A1.
List of Principal Investigators by Site
| CAEL101-301 List of Investigators Who Enrolled Patients | |||
|---|---|---|---|
| Country | Site No. | Address | Investigator Name |
| Australia | 5001 | Eastern Health – Box Hill Hospital 8 Arnold Street Box Hill, Victoria Australia 3128 |
Stephen Bek Ngie Ting, MBBS (Hons), FRCPA, FRACP, PhD |
| 5003 | Princess Alexandra Hospital 199 Ipswich Road, Woolloongabba Brisbane, Queensland Australia 4102 |
Peter Norman Mollee, MBBS, ECFMG, FRACP, FRCPA | |
| Austria | 3101 | Medizinische Universitatskilinik fur Innere Medizin I Wahringer Gurtel 18-20 Wien Austria 1090 |
Hermine Agis, MD, PhD |
| 3102 | Ordensklinikum Linz GmbH Elisabethinen Fadingerstrabe 1 Linz Austria 4020 |
Irene Strassl, MD | |
| Belgium | 3001 | Institut Jules Bordet Rue Meylemeersch 90 Brussels Belgium 1070 |
Nathalie Meuleman, MD, PhD |
| 3002 | UZ Leuven – Gasthuisberg Herestraat, 49 Leuven Belgium 3000 |
Michel Delforge, MD, PhD | |
| Canada | 1501 | Arthur Child J.E. Comprehensive Cancer Centre 3395 Hospital Drive NW Calgary, Alberta Canada T2N 5G2 |
Victor H. Jimenez Zepeda, MD |
| China | 5401 | Chinese Academy of Medical Sciences & Peking Union Medical College Hospital No. 1, Shuaifuyuan Dongcheng District, Beijing, China, 100730 |
Shuyang Zhang, MD |
| 5402 | Guangdong Provincial People's Hospital No. 106, Zhangshan Second Road Yuexiu District Guangzhou, Guangdong, China, 510080 |
Xin Du, MD | |
| 5404 | The Second Affiliated Hospital Zhejiang University School of Medicine No. 88, Jiefang Road Hangzhou, Zhejiang China 310009 |
Jianan Wang, MD | |
| 5408 | The First Affiliated Hospital of Wenzhou Medical University Nanbaixiang Ouhai District Wenzhou, Zhjiang China 325000 |
Honglan Qian, MD | |
| 5410 | Union Hospital Tongji Medical College Huazhong University of Science and Technology No. 1227 Jiefang Avenue Wuhan, Hubei China 430022 |
Chunyan Sun, MD | |
| 5408 | The First Affiliated Hospital of Wenzhou Medical University Nanbaixiang Ouhai District Wenzhou, Zhjiang China 325000 |
Honglan Qian, MD | |
| 5410 | Union Hospital Tongji Medical College Huazhong University of Science and Technology No. 1227 Jiefang Avenue Wuhan, Hubei China 430022 |
Chunyan Sun, MD | |
| Czech Republic | 3202 | Vseobecne fakultni nemocnice v Praze U Nemocnice 499/2 Prague Czech Republic 128 08 |
Frantisek Sedlak, MD |
| France | 2201 | CHU de Limoges – Hematologie Clinique et Therapie Cellulaire 2 Avenue Martin Luther King Limoges France 87042 |
Arnaud Jaccard, MD |
| 2202 | Hopital Henri Mondor – Unite Hemopathies Lymphoides 51, Avenue du Marechal de Lattre de Tassigny Creteil France 94010 |
Karim Belhadj, MD | |
| 2203 | Hopital Saint-Louis Service d'Immuno-Hematologie 1, Avenue Claude Vellefaux Paris France 75010 |
Bertrand Arnulf, MD | |
| 2204 | Centre Hospitalier Lyon Sud – Service d'Hematologie Clinique Pavillon Marcel Berard 165 Chemin du Grand Revoyet Peirre-Benite France 69495 |
Lionel Karlin, MD | |
| 2205 | Institut d'hematologie de Basse Normandie, CHU Caen Avenue de la cote de Nacre Caen Cedex France 14033 |
Margaret Macro, MD | |
| 2207 | Institut Paoli Calmettes – Hematologie 232 Boulevard Sainte Marguerite Marseille France 13009 |
Jean-Marc Schiano De Colella, MD (current) Anne-Marie Stoppa, MD (previous) |
|
| 2209 | Centre Hospitalier Universitaire, Hopital Jean Bernard Service de Nephrologie et transplantation renale 2 rue de la Miletrie Poitiers France 86021 |
Frank Bridoux, MD, PhD | |
| 2210 | CHU Tours, Hopital Bretonneau Centre Regional de Cancerologie Henri Kaplan, Service d'hematologie et Therapie cellulaire 2, Boulevard Tonnelle Tours Cedex 01 France 37044 |
Thomas Chalopin, MD | |
| 2212 | CHU de Bordeaux Groupe hospitalier Sud – Hopital Haut Leveque Service de Medecine interne et maladies infectieuses 2 Avenue de Magellan Pessac France 33604 |
Jean-Francois Viallard, MD, PhD | |
| 2213 | CHU Toulouse Hopital Ranguell, Service de Nephrologie-Transplantation 1, Avenue Jean Poulhes Toulouse France 31059 |
Antoine Huart, MD | |
| Germany | 2402 | Universitatsklinikum Essen AoR, Knik fur Hamatolgie Hufelandstrasse 55 Essen Germany 45147 |
Alexander Carpinteiro, MD |
| 2403 | Universitätsklinikum Düsseldorf, Klinik fur Hamatologie, Onkologie und Klinische Immunologie Moorenstraße 5 Düsseldorf Germany 40225 |
Roland Fenk, MD | |
| 2404 | Hämatologisch-Onkologische Praxis Altona HOPA MVZ GmbH Ärztezentrum Struenseehaus, Mörkenstr. 47 Hamburg Germany 22767 |
Timon Hansen, MD | |
| 2405 | Charité, Berlin Campus Benjamin Franklin (CBF), Klink mit Schwerpunkt Hamatologie, Onkologie und Tumorimmunologie Hindenburgdamm 30 Berlin Germany 12203 |
Vera Girke, MD (current) Axel Nogai, MD (previous) |
|
| Greece | 2801 | General Hospital of Althens “Alexandra” 80 Vasilissis Sofias Avenue Athens, Attica Greece 11528 |
Efstathios Kastritis, MD |
| 2802 | University Hospital of Patras Patra, Achaia Greece, 26504 |
Argiris (Anargyros) Symeonidis, MD | |
| Israel | 4001 | Hadassah Medical Center Kiryat Hadassah, Ein Kerem, POB 12000 Jerusalem Israel 9112001 |
Moshe Gatt, MD |
| 4004 | Rambam Health Care Campus HaAliya HaShniya St 8 Haifa Israel 3109601 |
Noa Lavi, MD | |
| 4005 | Sheba Medical Center Derech Sheba 2 Ramat Gan Israel 5266202 |
Hila Magen, MD | |
| Italy | 2301 | Fondazione IRCCS Policlinico S. Matteo Viale Golgi 19 (Pavia) Pavia Italy 27100 |
Giovanni Palladini, MD, PhD |
| 2302 | Fondazione Policlinico Universitario Campus Bio-Medico Via Álvaro del Portillo, 200 Rome, Italy Hematology unit, second floor Rome Lazio Italy 00128 |
Ombretta Annibali, MD | |
| 2303 | AOU Federico II, UOC Ematologia e Trapianti Via Sergio Pansini, 5 Naples Italy 80131 |
Fabrizio Pane, MD | |
| 2305 | Azienda Ospedaliera Universitaria Pisana Via Roma, 67 Pisa EU Italy 56126 |
Gabriele Buda, MD, PhD | |
| Japan | 5201 | Japanese Red Cross Medical Center 4-1-22 Hiroo Shibuya-ku Tokyo Japan 150-8935 |
Tadao Ishida, MD (current) Kenshi Suzuki, MD (previous) |
| 5202 | Nagoya City University Hospital 1 Kawasumi Mizuho-cho, Mizuho-ku Nagoya, Aichi Japan 467-8602 |
Shinsuke Iida, MD, PhD | |
| 5203 | Fukushima Medical University Hospital 1, Hikarigaoka Fukushima, Fukushima Japan 960-1295 |
Takayuki Ikezoe, MD | |
| Poland | 2704 | Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny, Klinika Hematologii, Transplantologii i Chorób Wewnętrznych UI. Banacha 1a Warszawa Poland 02-097 |
Krzysztof Jamroziak, MD |
| South Korea | 5301 | Seoul National University Hospital 101 Daehak-ro, Jongno-gu Seoul Republic of Korea 03080 |
Jamin Byun, MD, PhD (current) Youngil Koh, MD, PhD (previous) |
| 5304 | Samsung Medical Center 81, Irwon-ro, Gangnam-gu Seoul Republic of Korea 06351 |
Kihyun Kim, MD, PhD | |
| Spain | 2101 | Clinica Universidad de Navarra Av. Pio X11 55 Pamplona, Navarra Spain 31008 |
Ramon Lecumberri Villamediana, MD, PhD |
| 2102 | Hospital Clinic de Barcelona Calle Villarroel, 170 Barcelona Spain 08036 |
Maria Teresa Cibeira Lopez, MD, PhD | |
| 2103 | Hospital Universitario Puerta de Hierro Calle Joaquin Rodrigo, 1 Majadahonda, Madrid Spain 28222 |
Irene Romera Martinez, MD PhD (current) Rafael F. Duarte, MD, PhD, FRCP Lon (previous) Rafael Rios, MD, PhD (previous) Isabel Angela Krsnik Castello, MD, PhD (previous) |
|
| 2105 | Hospital Universitario de Cabuenes c/los Prados, 395 Gijon, Asturias Spain 33394 |
Maria Esther Gonzalez Garcia, MD, PhD | |
| 2106 | Hospital Universitario Virgen del Rocio Av. Manuel Siurot, s/n Sevilla Spain 4103 |
Eusebio Narciso Martin Chacon, MD (current) Javier Alberto Rojas Martinez, MD (previous) |
|
| United Kingdom | 2001 | University College London Hospital Haematology Clinical Trials 250 Euston Road, 1st Floor Central London United Kingdom NW1 2PG |
Ashutosh Wechalekar, MBBS, MD, FRCP, FRCpath, DM |
| United States | 1003 | Cleveland Clinic Taussig Cancer Center 9500 Euclid Avenue, Cleveland, OH 44195 |
Jason Valent, MD |
| 1004 | Stanford Cancer Institute 875 Blake Wilbur Drive Stanford, CA 94305 |
Michaela Liedtke, MD | |
| 1005 | City of Hope (City of Hope National Medical Center, City of Hope Medical Center) 1500 East Duarte Road Duarte, CA 91010 |
Michael A. Rosenzweig, MD | |
| 1006 | University of California, San Francisco Medical Center 400 Parnassus Avenue San Francisco, CA 94143 |
Alfred Chung, MD (current) Sandy Wong, MD (previous) |
|
| 1007 | The Ohio State University Wexner Medical Center/James Cancer Hospital 460 W. 10th Avenue Columbus, OH 43210 |
Naresh Bumma, MD | |
| 1009 | Columbia University Irving Medical Center – Herbert Irving Pavilion 161 Fort Washington Avenue New York, NY 10032 |
Divaya Bhutani, MD | |
| 1010 | Dana-Farber Cancer Institute 450 Brookline Avenue Boston, MA 02215 |
Giada Bianchi, MD | |
| 1011 | Tufts Medical Center 800 Washington Street Boston, MA 02111 |
Raymond Comenzo, MD | |
| 1014 | The University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd. Houston, TX 77030 |
Mahmoud Gaballa, MD (current) Hans C. Lee, MD (previous) Gregory P. Kaufman, MD (previous) |
|
| 1015 | Oregon Health and Science University 3181 SW Sam Jackson Park Road Portland, OR 97239 |
Eva Medvedova, MD | |
| 1016 | University of Rochester Medical Center 601 Elmwood Avenue Rochester, NY 14642 |
Frank Passero, MD | |
| 1017 | Siteman Cancer Center 4500 Forest Park Avenue Saint Louis, MO 63108 |
Keith Stockerl-Goldstein, MD | |
| 1018 | University of Pennsylvania Abramson Cancer Center 3400 Civic Center Boulevard Philadelphia, PA 19104 |
Adam Waxman, MD | |
| 1019 | Boston Medical Center One Boston Medical Center Place Moakley-3 Boston, MA 02118 |
Vaishali Sanchorawala, MD | |
| 1020 | Froedtert Hospital & Medical College of Wisconsin Division of Hematology and Oncology 9200 W. Wisconsin Avenue Milwaukee, WI 53226 |
Anita D'Souza, MD | |
| 1021 | Fred Hutchinson Cancer Center 825 Eastlake Avenue East Seattle, WA 98109 |
Andrew Cowan, MD (current) Sarah Lee, MD (previous) Edward Libby, MD (previous) |
|
| 1023 | Mayo Clinic 200 First Street SW Rochester, MN 55905 |
Angela Dispenzieri, MD | |
| 1024 | Huntsman Cancer Institute, University of Utah 2000 Circle of Hope Salt Lake City, UT 84112 |
Amandeep Godara, MBBS (current) Tibor Kovacsovics, MD (previous) |
|
| 1025 | Henry-Joyce Cancer Clinic 1301 Medical Center Drive The Vanderbilt Clinic Nashville, TN 37232 |
Salyka M. Sengsayadeth, MD (current) Stacey Ann Goodman, MD (previous) |
|
| 1036 | Cleveland Clinic Florida Weston 2950 Cleveland Clinic Blvd Weston, FL 33331 |
Chakra Chaulagain, MD | |
| List of Investigators Who Did Not Enroll Patients | |||
|---|---|---|---|
| Country | Site No. | Address | Investigator Name |
| Australia | 5002 | Westmead Hospital Corner of Hewkesbury, Darcy Roads, Westmead Sydney, New South Wales Australia 2145 |
Fiona Sill Mei Kwok, MBBS, MD,FRAC,FRCPA |
| 5004 | Fiona Stanley Hospital 11 Robin Warren Drive Murdoch, Western Australia Australia 6150 |
Hasib Sidiqi, MBBS, FRACP, FRCPA | |
| 5005 | Royal Adelaide Hospital Port Road Adelaide, South Australia Australia 5000 |
Naomi Horvath, MD, FRACP, FRCPA | |
| Belgium | 3003 | Cliniques Universitaires Saint-Luc Avenue Hippocrate, 10 Brussels Belgium 1200 |
Marie-Christiane Vekemans, MD |
| Brazil | 6001 | Centro Gaucho Inegrado de Oncologia, Hematologia, Ensino e Pesquisa Rua Costa, 30, 3rd Floor Porto Alegre Rio Grande do Sul/rs Brazil 90110-270 |
Marcelo Eduardo Zanella Capra, MD, PhD |
| 6002 | Institiuto D'Or de Pesquisa e Ensino/Hospital Sao Rafael Av Sao Rafael, 2152, 6th Floor – Coordenacao de Pesquisa Bairro Sao Marcos Salvador BA Brazil 41253-190 |
Edvan de Querioz Crusoe, MD, PhD | |
| 6003 | Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo Rua Tenente Catao Roxo 2701 Bloco 3 – Subsolo Monte Alegre-Unidade de Pesquisa Clinica – UPC Ribeirao Preto SP Brazil 14051-140 |
Pedro Manoel Marques Garibaldi, MD | |
| 6004 | Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Av. Brigadeiro Faria Lima, 5544 – 2nd Floor Sao Jose do Rio Preto Sao Paulo/SP Brazil 15090-000 |
Carlos Eduardo Miguel, MD | |
| 6005 | Sociedade Beneficente Israelita Brasileira Hopsital Albert Einstein Avenida Albert Einstein, 627/701 – Morumbi 2 subsolo – Bloco A/Centro de Pesquisa Clinica Sao Paulo, SP Brazil 05652-900 |
Nelson Hamerschlak, MD | |
| 6006 | Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Av Dr Eneas de Carvalho Aguiar, 155 – 1st Floor Predio dos Ambulatorios – Crequeira Cesar Sao Paulo, SP Brazil 05403-000 |
Pedro Pereira Neffa, MD | |
| 6007 | Hospital do Cancer de Pernambuco Av. Druz Cabuga, 1597, Santo Amaro Recife, Pernambuco Brazil 50040-000 |
Reijane Alves de Assis, MD, PhD | |
| Canada | 1502 | Cross Cancer Institute 11560 University Avenue NW Edmonton, Alberta Canada T6G1Z2 |
Irwindeep Sandhu, MD (current) Christopher Venner, MD (previous) |
| 1503 | University Health Network-Princess Margaret Cancer Centre 610 University Avenue Toronto, Ontario Canada M5G2M9 |
Vishal Kukreti, MD | |
| China | 5403 | Zhongshan Hosptial Fudan University No.180 Fenglin Road, Xului District Shanghai China 200032 |
Peng Liu, MD |
| 5405 | The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, Zhejiang China 310003 |
Zhen Cai, MD | |
| 5406 | Peking University First Hospital No. 8 Xishiku Avenue, Xicheng District, Beijing China 100034 |
Yujun Dong, MD | |
| 5407 | Ruijin Hospital of Shanghai Jioatong University School of Medicine, No. 197 Ruijin 2nd Road Huangpu District Shanghai China 200011 |
Wei Jin, MD | |
| 5409 | Peking University Third Hospital No. 49 North Huayuan Road Haidian District, Beijing Beijing China 100191 |
Yida Tang, MD | |
| Czech Republic | 3201 | Fakultni nemocnice Ostrava Klinika Hematoonkologie 17. Iistopadu 1790/5 Ostrava Czech Republic 708 52 |
Roman Hajek, MUDr, CSc, PhD |
| 3203 | Fakultni nemocnice Olomouc I. P. Pavlova 185/6 Olomouc Czech Republic 779 00 |
Tomas Pika, MUDr, PhD | |
| 3204 | Fakultni nemocnice Brno Interni hematologicka a onkologicka klinika Jihlavska 20, Brno Brno Czechia 625 00 |
Pour Ludek, MUDr, PhD | |
| France | 2206 | Hopital Claude Huriez – CHU de Lille 1, rue Michel Polonowski Lille, France 59000 |
Salomon Manier, MD, PhD |
| 2208 | Hopital Pontchaillou – CHU de Rennes Service d'Hematologie 2, rue Henri Le Guilloux Rennes Cedex 09 France 35033 |
Olivier Decaux, MD | |
| 2211 | CHU Dijon Bourgogne Hopital Francois Mitterrand Service d'hematologie clinique 14, rue Paul Gaffarel Dijon France 21079 |
Jean-Noel Bastie, MD (current) Denis Caillot, MD (previous) |
|
| Germany | 2401 | Universitatsklinikum Heidelberg, Innere Medizin V, Amyloidose- ZantrumIm Neuenheimer Feld 410 Geb 6410 Heidelberg Germany 69120 |
Stefan Schonland, MD |
| 2406 | Universitätsklinikum Münster, Medizinische Klinik A Albert-Schweitzer-Campus 1, Gebäude A1 Münster Germany, 48149 |
Cyrus Khandanpour, MD | |
| 2407 | Universitätsklinikum Würzburg, Oberdürrbacher Straße 6 Würzburg Germany 97080 |
Maximilian Steinhardt, MD (current) Stefan Knop, MD (previous) |
|
| 2408 | Universitatsmedizin Mainz, III Med Klinik und Poliklinik Langeckstr 1 Mainz Germany 55131 |
Markus Munder, MD | |
| Greece | 2803 | Ahepa University General Hospital Kyriakidis 1 Thessaloniki Greece 54636 |
Evdoxia Hatjiharissi, MD, PhD |
| Israel | 4002 | The Sourasky Tel Aviv Medical Center Weizmann St 6 Tel Aviv Israel 6423906 |
Yael Cohen, MD |
| 4003 | Institute of Hematology, Rabin Medical Center, Beilinson Hospital Jabutinsky Road 39 Petah Tikva Israel 4941492 |
Iulianna (Julia) Vaxman, MD | |
| Italy | 2304 | ASST Spedali Civili di Brescia, P.le Spedali Civili,1, S.C. Ematologia, Scala 11 piano 0, Brescia Lombardia Italy 25123 |
Alessandra Tucci, MD |
| 2306 | Ospedale San Giovanni Bosco, Piazza del Donatore di Sangue, 3, Ambulatori nefrologia e dialisi, 4th floor Nuova Piastra Torino, Piemonte Italy 10154 |
Dario Roccatello, MD | |
| Japan | 5208 | Shinshi University Hospital Asahi 3-1-1, Matsumoto-shi, Nagano-Ken Japan 390-8621 |
Nagaaki Kato, MD |
| The Netherlands | 3301 | University Medical Centre Utrecht, P.O. Box 85500 Utrecht The Netherlands 3508 GA |
Monique Minnema, MD |
| 3302 | University Medical Center Amsterdam De Boelelaan 1117, 1081HV Amsterdam Amsterdam The Netherlands 1081HV |
Kaz Groen, MD | |
| 3303 | University Medical Center Groningen Postbus 30.001 Groningen The Netherlands 9700 RB |
Wilfried Roeloffzen, MD | |
| 3304 | Haga Hospital Hagaziekenhuis Route E0.4 Els Borst – Eilersplein 275 Den Hag The Netherlands 2545 AA |
Paula Ypma, MD, PhD | |
| Poland | 2703 | Uniwersyteckie Centrum Kliniczne, UI. Smoluchowskiego 17, Gdańsk Poland 80-214 |
Monika Szarejko, MD (current) Jan Zaucha, MD (previous) |
| 2705 | Uniwersytecki Szpital Kliniczny w Poznaniu, Oddziat Hematologii I Transplantacji Szpiku UI. Szamarzewskiego 84 Poznan Poland 60-569 |
Dominik Dytfeld, MD | |
| Russia | 2901 | Russian Federation City of St. Petersburg Rentgena Street 12 bld 43, room 217 Saint-Petersburg Russia 197022 |
Ivan Moisseev, MD |
| 2902 | V. A. Almazov National Medical Research Center 2, Akkuratova Street Saint-Petersburg Russia 197341 |
Galina Salogub, MD | |
| 2903 | The Sechenov First Moscow State Medical University, 8-2 Trubetskaya Street Moscow Russia 119991 |
Lidiya Lysenko, MD | |
| 2904 | National Medical Research Center of Hematology 4, Noviy Zykovskiy proezd, Moscow Russia 125167 |
Larisa Mendeleeva, MD | |
| Republic of Korea | 5302 | Severance Hospital 50-1, Yonsei-ro Seodaemun-gu, Seoul Republic of Korea 03722 |
Jin Seok Kim, MD |
| 5303 | Catholic University of Korea, Seoul St. Mary’s Hospital 222 Banpo-daero, Seochu-gu, Seoul Republic of Korea, 06591 |
Chang Ki Min, MD | |
| Spain | 2104 | Hospital Universitario Vall d'Hebron Passeig Vall d'Hebron 119/129 Barcelona Community of Catalunya Spain 08035 |
Mercedes Gironella Mesa, MD |
| 2107 | Hospital Clinico Universitario de Salamanca Paseo de San Vicentre 182 Salamanca Spain 37007 |
Veronica Gonzalez de la Calle, MD (current) Beatriz Rey, MD (previous) |
|
| 2108 | Hospital Universitario Virgen de Las Nives Avenida de las Fuerzas Armadas 2 Granada Spain 18014 |
Maria Esther Clavero Sanchez, MD | |
| 2109 | Hosptial Universitario y Politecnico la Fe Avda Fernando Abril Martoreli, 106 Valencia Spain 46026 |
Francisco Javier e La Rubia Comos, MD | |
| 2110 | Hospital La Luz C/del Maestro Angel Llorca, 8 Madrid Spain 28003 |
Roberto Martin Reves, MD | |
| 2111 | Funacion Jimenez Diaz Avenida de los Reyes Catolicos, 2 Madrid Spain 28040 |
Elham Askari, MD | |
| Switzerland | 3402 | CHARMS Studienkoordination Murtenstrasse 21 3010 Bern, Floor 4 Office 407, Bern, Bern Switzerland 3010 |
Martin Andres |
| United Kingdom | 2002 | The Clatterbridge Cancer Centre NHS Foundation Trust Clatterbridge Rd Birkenhead, Wirral United Kingdom CH63 4JY |
Stephen Hawkins, MD |
| 2003 | The Beatson West of Scotland Cancer Centre 1053 Great Western Road Glasgow United Kingdom G12 0YN |
Jennifer Travers, MD | |
| United States | 1001 | Karmanos Cancer Institute 4100 John R Street Detroit, MI 48201 |
Jeffrey Zonder, MD |
| 1002 | Memorial Sloan Kettering Basking Ridge 136 Mountain View Blvd Basking Ridge, NJ 07920 |
Heather Landau, MD | |
| 1008 | Indiana University Melvin and Bren Simon Comprehensive Cancer Center 535 Barnhill Drive Indianapolis, IN 46202 |
Rafat Abonour, MD | |
| 1012 | Duke University Health System 2400 Pratt Street Suite 1100 Durham, NC 27705 |
Cristiana Costa Chase, DO | |
| 1022 | University of North Carolina at Chapel Hill, Houpt Building 170 Manning Drive Chapel Hill NC, 27599-7305 |
Sascha Tuchman, MD | |
| 1027 | Mayo Clinic Florida 4500 San Pablo Road Jacksonville, FL 32224 |
Taimur Sher, MD | |
| 1028 | Mayo Clinic Building – Phoenix 5881 E. Mayo Boulevard Phoenix, AZ 85054 |
Rafael Fonseca, MD | |
| 1029 | University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390 |
Larry Anderson, MD | |
| 1030 | New York Presbyterian Hospital/Well Cornell Medical Center 525 East 68th Street, Starr 3, New York, NY10065 |
Cara Rosenbaum, MD | |
| 1031 | Houston Methodist Hospital 6550 Fannin Street Houston, TX 77030 |
Barry H. Trachtenberg, MD | |
| 1035 | Atrium Health Wake Forest Baptist Health 1 Medical Center Blvd Winston-Salem, NC 27157 |
David Hurd, MD | |
| 1038 | Tulane Medical Center 1415 Tulane Avenue New Orleans, LA 70112 |
Hana Safah, MD | |
| 1040 | University of Maryland Greenebaum Comprehensive Cancer Center 22 South Greene Street Baltimore, MD 21201 |
Mehmet Hakan Kocoglu, MD | |
| CAEL101-302 List of Investigators | |||
|---|---|---|---|
| Country | Site No. | Address | Investigator Name |
| Australia | 5001 | Eastern Health – Box Hill Hospital 8 Arnold Street Box Hill, Victoria Australia 3128 |
Stephen Bek Ngie Ting, MBBS (Hons), PhD, FRCPA, FRACP (current) Simon Gibbs, MBBS, FRACP, FRCPA (previous) |
| 5002 | Westmead Hospital Corner of Hewkesbury, Darcy Roads, Westmead Sydney, New South Wales Australia 2145 |
Fiona Sill Mei Kwok, MBBS,MD,FRACP,FRCPA | |
| 5003 | Princess Alexandra Hospital 199 Ipswich Road, Woolloongabba Brisbane, Queensland Australia 4102 |
Peter Norman Mollee, MBBS, ECFMG,FRACP, FRCPA | |
| 5004 | Fiona Stanley Hospital, 11 Robin Warren Drive Murdoch, Western Australia Australia, 6150 |
Hasib Sidiqi, MBBS, FRACP, FRCPA | |
| Austria | 3101 | Medizinische Universitatskilinik fur Innere Medizin I Wahringer Gurtel 18-20 Wien Austria 1090 |
Hermine Agis, MD, PhD |
| Brazil | 6001 | Centro Gaucho Inegrado de Oncologia, Hematologia, Ensino e Pesquisa LTDA – Hospital Mae de Deus/AESC Rua Costa, 30 3rd andar – Menino Deus, Porto Alegre, Rio Grande do Sul/rs Brazil 90470-340 |
Marcelo Eduardo Zanella Capra, PhD, MD |
| 6003 | Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo Rua Tenente Catao Roxo 2701 Bloco 3 – Subsolo Monte Alegre-Unidade de Pesquisa Clinica – UPC Ribeirao Preto SP Brazil 14051-140 |
Pedro Manoel Marques Garibaldi, MD | |
| Canada | 1501 | Arthur Child J.E. Comprehensive Cancer Centre 3395 Hospital Drive NW Calgary, Alberta Canada T2N 5G2 |
Victor Jimenez Zepeda, MD |
| 1503 | University Health Network- Princess Margaret Cancer Centre 610 University Avenue Toronto, Ontario Canada M5G2M9 |
Vishal Kukreti, MD, MSc, BSc | |
| China | 5401 | Chinese Academy of Medical Sciences & Peking Union Medical College Hospital No. 1, Shuaifuyuan, Dongcheng District, Beijing China 100730 |
Jian Li, MD |
| 5402 | Guangdong Provincial People's Hospital No. 106, Zhongshan Second Road, Yuexiu District Guangzhou, Guangdong China 510080 |
Xin Du, MD | |
| 5403 | Zhongshan Hospital Fudan University No. 180 Fenglin Road, Xuhui District Shanghai China 200032 |
Peng Liu, MD | |
| 5404 | The Second Affiliated Hospital Zhejiang University School of Medicine No. 88, Jiefang Road Hangzhou, Zhejiang China 310009 |
Jianan Wang, MD | |
| 5411 | The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road Suxhou, Jiangsu China 215006 |
Chengcheng Fu, MD | |
| Czech Republic | 3201 | Fakultni nemocnice Ostrava 17 Iistopadu 1790/5 Ostrava Czech Republic 708 52 |
Roman Hajek, MUDr, CSc, PhD |
| 3202 | Vseobecne fakultni nemocnice v Praze U Nemocnice 499/2 Prague Czech Republic 128 08 |
Frantisek Sedlak, MD | |
| France | 2201 | CHU de Limoges – Hematologie Clinique et Therapie Cellulaire 2 avenue Martin Luther-King Limoges France 87042 |
Arnaud Jaccard, MD |
| 2202 | Hopital Henri Mondor – Unite Hemopathies Lymphoides 51, Avenue du Marechal de Lattre de Tassigny Creteil France 94010 |
Karim Belhadj, MD | |
| 2204 | Centre Hospitalier Lyon Sud – Service d'Hematologie Clinique Pavillon Marcel Berard 165 Chemin du Grand Revoyet Pierre-Benite France 69495 |
Lionel Karlin, MD | |
| 2205 | Institut d'hematologie de Basse Normandie, CHU Caen Avenue de la cote de Nacre Caen Cedex France 14033 |
Margaret Macro, MD | |
| 2207 | Institut Paoli Calmettes – Hematologie 232 boulevard Sainte Marguerite Marseille France 13009 |
Jean-Marc Schiano De Colella, MD (current) Anne-Marrie Stoppa, MD (previous) |
|
| 2209 | Centre Hospitalier Universitaire, Hopital Jean Bernard Service de Nephrologie et transplantation renale 2 rue de la Miletrie Poitiers France 86021 |
Frank Bridoux, MD, PhD | |
| 2210 | CHU Tours, Hopital Bretonneau Centre Regional de Cancerologie Henri Kaplan, Service d'hematologie et Therapie cellulaire 2, Boulevard Tonnelle Tours Cedex 01 France 37044 |
Thomas Chalopin, MD | |
| 2211 | CHU Dijon Bourgogne Hopital Francois mitterrand, Service d'hematologie clinicque 14, rue Paul Gaffarel Dijon France 21079 |
Jean-Noel Bastie, MD (current) Denis Caillot, MD (previous) |
|
| 2212 | CHU de Bordeaux Groupe hospitalier Sud – Hopital Haut Leveque Service de Medecine interne et maladies infectieuses 2 Avenue de Magellan Pessac France 33604 |
Jean-Francois Viallard, MD, PhD | |
| 2213 | CHU Toulouse Hopital Ranguell, Service de Nephrologie-Transplantation 1, Avenue Jean Poulhes Toulouse France 31059 |
Antoine Huart, MD | |
| Germany | 2401 | Universitatsklinikum Heidelberg Innere Medizin V Amyloidose-Zantrum Im Neuenheimer Feld 410, Geb 6410 Heidelberg Germany 69120 |
Stefan Schonland, MD |
| 2402 | Universitatsklinikum Essen AoR Klinik fur Hamatologie Hufelandstrasse. 55 Essen Germany 45147 |
Alexander Carpinteiro, MD | |
| 2403 | Universitätsklinikum Düsseldorf, Klinik fur Hamatologie, Onkologie und Klinische Immunologie Moorenstrabe 5 Dusseldorf Germany 40225 |
Roland Fenk, MD | |
| 2404 | Hämatologisch-Onkologische Praxis Altona HOPA MVZ GmbH Ärztezentrum Struenseehaus Mörkenstrasse 47 Hamburg Germany 22767 |
Timon Hansen, MD | |
| 2405 | Charité, Campus Benjamin Franklin (CBF) Klinik mit Schwerpunkt Hamatologie, Onkologie und Tumorimmunologie Hindenburgdamm 30 Berlin Germany 12203 |
Vera Girke, MD (current) Axel Nogai, MD (previous) |
|
| Greece | 2801 | General Hospital of Althens “Alexandra” 80 Vasilissis Sofias Avenue Athens, Attica Greece 11528 |
Efstathios Kastritis, MD |
| 2803 | Ahepa University General Hospital Kyriakidis 1 Thessaloniki Greece 54636 |
Evdoxia Hatjiharissi, MD, PhD | |
| Israel | 4001 | Hadassah Medical Center Kiryat Hadassah, Ein Kerem POB 12000 Jerusalem Israel 9112001 |
Moshe Gatt, MD |
| 4002 | The Sourasky Tel Aviv Medical Center Weizmann St 6 Tel Aviv Israel 6423906 |
Yael Cohen, MD | |
| 4003 | Institute of Hematology Rabin Medical Center Beilinson Hospital Jabutinsky Road 39 Petah Tikva Israel 4941492 |
Iuliana Vaxman, MD | |
| 4004 | Rambam Health Care Campus HaAliya HaShniya St 8 Haifa Israel 3109601 |
Noa Lavi, MD | |
| 4005 | Sheba Medical Center Derech Sheba 2 Ramat Gan Israel 5266202 |
Hila Magen, MD | |
| Italy | 2304 | ASST Spedali Civili Brescia Piazzale Spedali Civili N.1 Ematologia DH, scala 11 piano terra Brescia Lombardia Italy 25123 |
Alessandra Tucci, MD |
| Japan | 5201 | Japanese Red Cross Medical Center 4-1-22 Hiroo Shibuya-ku Tokyo Japan 150-8935 |
Tadao Ishida, MD (current) Kenshi Suzuki, MD (previous) |
| 5202 | Nagoya City University Hospital 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi Japan 467-8602 |
Shinsuke Iida, MD, PhD | |
| 5204 | Japan Community Healthcare Organization Kyoto Kuramaguchi Medical Center 27, Shimofusa-cho, Koyama Kita-ku Kyoto-City Kyoto Japan 603-8151 |
Chihiro Shimazaki, MD | |
| 5205 | Kumamoto University Hospital Chuo-ku Honjo 1-1-1 Kumamoto-shi Kumamoto-Ken Japan 860-8556 |
Yawara Kawano, MD | |
| 5206 | The Jikei University Kashiwa Hospital 163-1 Kashiwashita Kashiwa-city Chiba Japan 277-0004 |
Kaichi Nishiwaki, MD (current) Kazuhito Suzuki, MD (previous) |
|
| 5207 | Kanazawa University Hospital Takara-machi 13-1 Kanazawa-shi Ishikawa Japan 920-8641 |
Toshihiro Miyamoto, MD (current) Hiroyuki Takamatsu, MD (previous) |
|
| 5208 | Shinshi University Hospital Asahi 3-1-1 Matsumoto-shi Nagano-Ken Japan 390-8621 |
Nagaaki Kato, MD | |
| Poland | 2704 | Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny, Klinika Hematologii, Transplantologii i Chorób Wewnętrznych UI. Banacha 1a Warszawa Poland 02-097 |
Krzysztof Jamroziak, MD |
| Russia | 2901 | FSBEI of HE “Acad. I.P. Pavlov First St. Petersburg State Medical University Medical University” of the MoH of Russia 12, bld. 43, Rentgena Street Saint-Petersburg Russia 197022 |
Ivan Moiseev, MD |
| Republic of Korea | 5302 | Severance Hospital, Yonsei University Health System 50-1, Yonsei-ro, Seodaemun-gu Seoul Republic of Korea 03722 |
Jin Seok Kim, MD, PhD |
| 5303 | The Catholic University of Korea, Seoul St. Mary’s Hospital 222, Banpo-daero, Seocho-gu Seoul Republic of Korea 06591 |
Chang-Ki Min, MD, PhD | |
| 5304 | Samsung Medical Center 81, Irwon-ro, Gangnam-gu Seoul Republic of Korea 06351 |
Kihyun Kim, MD, PhD | |
| Spain | 2101 | Clinica Universidad de Navarra Av. Pio XII 55, Pamplona, Navarra Spain 31008 |
Ramon Lecumberri Villamediana, MD, PhD |
| 2102 | Hospital Clinic de Barcelona Calle Villarroel, 170 Barcelona Spain, 08036 |
Maria Teresa Cibeira Lopez, MD, PhD | |
| 2103 | Hospital Universitario Puerta de Hierro Calle Joaquin Rodrigo, 1 Majadahonda Madrid Spain 28222 |
Irene Romera Martinez, MD, PhD (current) Rafael F. Duarte, MD, PhD, FRCP Lon (previous) Rafael Rios, MD, PhD (previous) Isabel Angela Krsnik Castello, MD, PhD (previous) |
|
| 2104 | Hospital Universitario Vall d'Hebron Passeig Vall d'Hebron, 119/129 Barcelona, Community of Catalunya Spain 08035 |
Mercedes Gironella Mesa, MD | |
| 2105 | Hospital Universitario de Cabuenes c/los Prados, 395 Gijon, Asturias Spain 33394 |
Maria Esther Gonzalez Garcia, MD, PhD | |
| 2106 | Hospital Universitario Virgen del Rocio Av. Manuel Siurot s/n Sevilla Spain 4103 |
Eusebio Narciso Martin Chacon, MD (current) Javier Alberto Rojas Martinez, MD (previous) |
|
| 2108 | Hospital Universitario Virgen de Las Nieves Avda. Fuerzas Armadas, 2 Granada Spain 18014 |
Maria Esther Clavero Sanchez, MD | |
| 2110 | Hospital La Luz C/del Maestro Angel Llorca, 8 Madrid Spain 28003 |
Roberto Martin Reves, MD | |
| 2111 | Fundacion Jimenez Diaz Avenida de los Reyes Catolicos, 2 Madrid Spain 28040 |
Elham Askari, MD | |
| United Kingdom | 2001 | University College London Hospital Haematology Clinical Trials 250 Euston Road 1st Floor East Central London United Kingdom NW1 2PG |
Ashutosh Wechalekar, MBBS, MD, FRCP, FRCpath, DM |
| United States | 1001 | Karmanos Cancer Institute 4100 John R Street Detroit, MI 48201 |
Jeffrey Zonder, MD |
| 1002 | Memorial Sloan Kettering Cancer Center 1275 York Avenue, New York, NY 10065 |
Heather Landau, MD | |
| 1003 | Cleveland Clinic Taussig Cancer Center 9500 Euclid Avenue Cleveland, OH 44195 |
Jason Valent, MD | |
| 1004 | Stanford Cancer Institute 875 Blake Wilbur Drive Stanford, CA 94305 |
Michaela Liedtke, MD | |
| 1005 | City of Hope (City of Hope National Medical Center, City of Hope Medical Center) 1500 East Duarte Road Duarte, CA 91010 |
Michael Alan Rosenzweig, MD | |
| 1006 | University of California, San Francisco Medical Center 400 Parnassus Avenue San Francisco, CA 94143 |
Alfred Chung, MD (current) Sandy Wong, MD (previous) |
|
| 1007 | The Ohio State University Wexner Medical Center/James Cancer Hospital 460 W. 10th Avenue Columbus, OH 43210 |
Naresh Bumma, MD | |
| 1008 | Indiana University Melvin and Bren Simon Comprehensive Cancer Center 535 Barnhill Drive Indianapolis, IN 46202 |
Rafat Abonour, MD | |
| 1009 | Columbia University Irving Medical Center 161 Fort Washington Ave, Herbert Irving Pavilion New York, NY 10032 |
Divaya Bhutani, MD | |
| 1010 | Dana-Farber Cancer Institute 450 Brookline Avenue Boston, MA 02215 |
Giada Bianchi, MD | |
| 1011 | Tufts Medical Center 800 Washington Street Boston, MA 02111 |
Raymond Comenzo, MD | |
| 1012 | Duke University Health System: Adult Bone Marrow Transplant Clinic 2400 Pratt Street Suite 1100 Durham, NC 27705 |
Cristiana Costa Chase, DO (current) Cristina Gasparetto, MD (previous) Cristiana Costa Chase, DO (previous) |
|
| 1014 | The University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd Houston, TX 77030 |
Mahmoud Gaballa, MD (current) Hans C. Lee, MD (previous) Greg Kaufman, MD (previous) |
|
| 1015 | Oregon Health and Science University 3181 SW Sam Jackson Park Road Portland, OR 97239 |
Eva Medvedova, MD | |
| 1016 | University of Rochester Medical Center 601 Elmwood Avenue Rochester, NY 14642 |
Frank Passero, MD | |
| 1017 | Siteman Cancer Center 4500 Forest Park Avenue Saint Louis, MO 63108 |
Keith Stockerl- Goldstein, MD | |
| 1018 | Hospital of the University of Pennsylvania Perelman Center for Advanced Medicine 3400 Civic Center Boulevard Philadelphia, PA 19104 |
Adam Waxman, MD | |
| 1019 | Boston Medical Center One Boston Medical Center Place, 830 Harrison Avenue Moakley-3 Boston, MA 02118 |
Vaishali Sanchorawala, MD | |
| 1020 | Froedtert Hospital & the Medical College of Wisconsin 9200 W. Wisconsin Avenue Milwaukee, WI 53226 |
Anita D'Souza, MD | |
| 1021 | Fred Hutchinson Cancer Centre 825 Eastlake Avenue East Seattle, WA 98109 |
Andrew Cowan, MD (current) Sarah Lee, MD (previous) Edward Libby, MD (previous) |
|
| 1022 | University of North Carolina Hospitals at Hillsborough 430 Waterstone Drive Hillsborough, NC 27278 |
Sascha Tuchman, MD | |
| 1023 | Mayo Clinic 200 First Street SW Rochester, MN 55905 |
Angela Dispenzieri, MD | |
| 1024 | Huntsman Cancer Institute, University of Utah 2000 Circle of Hope Salt Lake City, UT 84112 |
Amandeep Godara, MBBS (current) Tibor Kovascovics, MD (previous) |
|
| 1025 | Henry-Joyce Cancer Clinic 1301 Medical Center Drive The Vanderbilt Clinic Nashville, TN 37232 |
Salyka M. Sengsayadeth, MD (current) Stacey Ann Goodman, MD (previous) |
|
| 1028 | Mayo Clinic 5881 E. Mayo Boulevard Phoenix, AZ 85054 |
Rafael Fonseca, MD (current) Craig B. Reeder, MD (previous) Jeremy Larsen, MD (previous) |
|
| 1029 | University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas TX 75390-8843 |
Larry Anderson, Jr, MD, PhD | |
| 1035 | Wake Forest Baptist Health Medical Center Blvd Winston-Salem NC 27157 |
David Hurd, MD | |
| 1036 | Cleveland Clinic Florida Weston 2950 Cleveland Clinic Blvd Weston, FL 33331 |
Chakra Chaulagain, MD | |
| 1040 | University of Maryland Greenebaum Comprehensive Cancer Center 22 South Greene Street Baltimore, MD 21201 |
Mehmet Hakan Kocoglu, MD | |
| 1043 | University of Wisconsin Carbone Cancer Center – University Hospital 600 Highland Avenue Madison, WI 53792 |
Timothy Schmidt, MD | |
| List of Investigators Who Did Not Enroll Patients | |||
|---|---|---|---|
| Country | Site No. | Address | Investigator Name |
| Australia | 5005 | Royal Adelaide Hospital Port Road Adelaide, South Australia Australia, 5000 |
Noemi Horvath, MD, FRACP, FRCPA |
| Austria | 3102 | Ordensklinikum Linz GmbH Elisabethinen Fadingerstrabe 1 Linz Austria 4020 |
Irene Strassl, MD |
| Belgium | 3001 | Institut Jules Bordet Rue Meylemeersch 90 Brussels Belgium 1070 |
Nathalie Meuleman, PhD, MD |
| 3002 | UZ Leuven – Gasthuisberg Herestraat, 49 Leuven Belgium 3000 |
Michel Delforge, PhD, MD | |
| 3003 | Cliniques Universitaires Saint-Luc Avenue Hippocrate,10 Brussels Belgium 1200 |
Marie-Christiane Vekemans, MD | |
| Brazil | 6002 | Institiuto D'Or de Pesquisa e Ensino/Hospital Sao Rafael Av Sao Rafael, 2152, 6th Floor – Coordenacao de Pesquisa Bairro Sao Marcos Salvador Bahia Brazil 41253-190 |
Edvan de Querioz Crusoe, MD, PhD |
| 6004 | Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Av. Brigadeiro Faria Lima, 5544 – 2nd Floor Sao Jose do Rio Preto Sao Paulo/SP Brazil 15090-000 |
Carlos Eduardo Miguel, MD | |
| 6005 | Sociedade Beneficente Israelita Brasileira Hopsital Albert Einstein Avenida Albert Einstein, 627/701 – Morumbi 2 subsolo – Bloco A/Centro de Pesquisa Clinica Sao Paulo, SP Brazil 05652-900 |
Nelson Hamerschlak, MD | |
| 6006 | Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Av Dr Eneas de Carvalho Aguiar, 155 – 1st Floor Predio dos Ambulatorios – Crequeira Cesar Sao Paulo, SP Brazil 05403-000 |
Pedro Pereira Neffa, MD | |
| 6007 | Hospital do Cancer de Pernambuco Av. Druz Cabuga, 1597, Santo Amaro Recife, Pernambuco Brazil 50040-000 |
Reijane Alves de Assis, MD, PhD | |
| Canada | 1502 | Cross Cancer Institute 11560 University Avenue NW Edmonton, Alberta Canada T6G 1Z2 |
Irwindeep Sandhu, MD, FRCPC, QIACM (current) Christopher Venner, MD, FRCPC (previous) |
| China | 5405 | The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, No. 79 Qingchun Road Hangzhou, Zhejiang China 310003 |
Zhen Cai, Prof, MD |
| 5406 | Peking University First Hospital No. 8 Xishiku Avenue Xicheng District Beijing China 100034 |
Yujun Dong, MD | |
| 5407 | Ruijin Hospital of Shanghai Jioatong University School of Medicine, No. 197 Ruijin 2nd Road Huangpu District Shanghai China 200011 |
Wei Jin, MD | |
| 5408 | The First Affiliated Hospital of Wenzhou Medical University Nanbaixiang, Ouhai District, Wenzhou, Zhjiang China 325000 |
Honglan Qian, MD | |
| 5410 | Union Hospital Tongji Medical College Huazhong University of Science and Technology No. 1227 Jiefang Avenue Wuhan, Hubei China 430022 |
Chunyan Sun, MD | |
| Czech Republic | 3203 | Fakultni nemocnice Olomouc I. P. Pavlova 185/6 Olomouc Czech Republic 779 00 |
Tomas Pika, MUDr, PhD |
| France | 2203 | Hopital Saint-Louis APHP – Service d'Immuno-Hematologie 1, Avenue Claude Vellefaux Paris France 75010 |
Bertrand Arnulf, MD |
| 2206 | Hopital Claude Huriez – CHU de Lille – Maladies du Sang 1, rue Michel Polonowski Lille France 59000 |
Salomon Manier, MD, PhD | |
| 2208 | Hopital Pontchaillou – CHU de Rennes Service d'Hematologie 2, rue Henri Le Guilloux Rennes Cedex 09, France 35033 |
Olivier Decaux, MD | |
| Germany | 2406 | Universitätsklinikum Münster, Medizinische Klinik A Albert-Schweitzer-Campus 1, Gebäude A1 Münster Germany 48149 |
Cyrus Khandanpour, MD |
| 2407 | Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Oberdürrbacher Straße 6 Würzburg Germany 97080 |
Maximilian Steinhardt, MD (current) Stefan Knop, MD (previous) |
|
| 2408 | Universitatsmedizin Mainz, III Med Klinik und Poliklinik Langeckstr 1 Mainz Germany 55131 |
Markus Munder, MD | |
| Greece | 2802 | University Hospital of Patra Rio, Patra, Achaia Greece, 26504 |
Argiris (Anargyros) Symeonidis, MD |
| Italy | 2301 | Fondazione IRCCS Policlinico San Matteo, Viale Golgi, 19 Pavia Italy 27100 |
Giovanni Palladini, MD |
| 2302 | Fondazione Policlinico Universitario Campus Bio-Medico Via Álvaro del Portillo, 200 Rome, Italy Hematology unit, 2nd Floor Rome Lazio Italy 00128 |
Ombretta Annibali, MD | |
| 2303 | AOU Federico II, UOC Ematologia e Trapianti Via Sergio Pansini, 5 Naples Italy 80131 |
Fabrizio Pane, MD | |
| 2305 | Azienda Ospedaliera Universitaria Pisana, Via Roma, 67, Pisa EU Italy 56126 |
Gabriele Buda | |
| 2306 | Ospedale San Giovanni Bosco Piazza del Sangue, 3, Torino, EU, Italy 10154 |
Dario Roccatello, MD | |
| Japan | 5203 | Fukushima Medical University Hospital, 1, Hikarigaoka Fukushima Japan 960-1295 |
Takayuki Ikezoe, MD |
| The Netherlands | 3301 | University Medical Centre Utrecht, P.O. Box 85500 Utrecht The Netherlands 3508 GA |
Monique Minnema, MD |
| 3302 | University Medical Center Amsterdam De Boelelaan 1117, 1081HV Amsterdam Amsterdam The Netherlands, 1081HV |
Kaz Groen, MD | |
| 3303 | University Medical Medical Center Groningen Postbus 30.001 Groningen The Netherlands, 9700 RB |
Wilfried Roeloffzen, MD | |
| 3304 | Haga Hospital Hagaziekenhuis Route E0.4 Els Borst – Eilersplein 275 Den Hag The Netherlands 2545 AA |
Paula Ypma, MD, PhD | |
| Poland | 2703 | Uniwersyteckie Centrum Kliniczne, UI. Smoluchowskiego 17 Gdańsk Poland 80-214 |
Monika Szarejko, MD (current) Jan Zaucha, MD (previous) |
| 2705 | Uniwersytecki Szpital Kliniczny w Poznaniu, Oddziat Hematologii I Transplantacji Szpiku UI. Szamarzewskiego 84 Poznan Poland 60-569 |
Dominik Dytfeld, MD | |
| Russia | 2902 | Federal State Budgetary Institution “V. A. Almazov National Medical Research Center” of the MoH of Russia, 2, Akkuratova Street Saint-Petersburg Russia 197341 |
Galina Salogub, MD |
| 2903 | Chair of inner, professional diseases and rheumatology based on Clinic of rheumatology, nephrology and professional pathology na. EM. Tareev of Sechenov University 11, bId. 5, Rossolimo Street Moscow Russia 119435 |
Lidiya Lysenko, MD | |
| 2904 | Federal state budgetary institution “National medical research center of hematology” of the MoH of the Russian Federation 4, Noviy Zykovskiy proezd, Moscow Russia 125167 |
Larisa Mendeleeva, MD | |
| South Korea | 5301 | Seoul National University Hospital, 101 Daehak-ro Jongno-gu Seoul Republic of Korea 03080 |
JaMin Byun, MD (current) Youngil Koh, MD (previous) |
| Spain | 2107 | Hospital Universitario de Salamanca Paseo San Vicente 58-182 Salamanca Spain 37007 |
Veronica Gonzalez de la Calle, MD (current) |
| 2109 | Hosptial Universitario y Politecnico la Fe Avda Fernando Abril Martorell, 106 Torre C, Planta 7, Consultas Externas Hematologia Valencia Spain 46026 |
Francisco Javier de La Rubia Comos, MD | |
| Switzerland | 3402 | Universitatspital fur Hamatologisches Zentrallabor, Freiburgstrasse Bern Bern Switzerland 3010 |
Martin Andres |
| United Kingdom | 2003 | The Beatson West of Scotland Cancer Centre 1053 Great Western Rd Glasgow United Kingdom G12 0YN |
Jennifer Travers, MD |
| United States | 1027 | Mayo Clinic Florida 4500 San Pablo Road Jacksonville FL 32224\ |
Taimur Sher, MD |
| 1030 | New York Presbbyterian Hospital/Well Cornell Medical Center 525 East 68th Street, Starr 3 New York, NY 100065 |
Cara Rosenbaum, MD | |
| 1031 | Houstan Methodist Hospital 6550 Fannin St, Suite 1901, Houston, TX 77030 |
Barry Trachtenberg, MD | |
| 1038 | Tulane Medical Center 1415 Tulane Avenue New Orleans, LA 70112 |
Hana Safah, MD | |
Ashutosh D. Wechalekar
Honoraria: Janssen-Cilag, Prothena, Alexion Pharmaceuticals
Consulting or Advisory Role: GlaxoSmithKline, Alexion Pharmaceuticals, ATTRALUS
Travel, Accommodations, Expenses: Janssen, AstraZeneca
Angela Dispenzieri
Research Funding: Celgene (Inst), Janssen Oncology (Inst), Pfizer (Inst), Takeda (Inst), Alexion Pharmaceuticals (Inst), AbbVie (Inst)
Vaishali Sanchorawala
Honoraria: Janssen, Prothena, Prothena, Gate Bioscience, AbbVie, GlaxoSmithKline, Eidos Therapeutics, Alexion Pharmaceuticals
Consulting or Advisory Role: Proclara, Caelum Biosciences, Janssen Research & Development, AbbVie, Regeneron, Protego Biopharma
Research Funding: Takeda (Inst), Celgene (Inst), Prothena (Inst), Janssen (Inst), Oncopeptides (Inst), Caelum Biosciences (Inst), Karyopharm Therapeutics (Inst), Immix BioPharma (Inst), Immix BioPharma (Inst)
Efstathios Kastritis
Honoraria: Genesis Pharma, Janssen Oncology, Takeda, Prothena, Pfizer, GlaxoSmithKline
Consulting or Advisory Role: Janssen Oncology, Takeda, Genesis Pharma, Prothena, Pfizer
Research Funding: Janssen Oncology (Inst), Amgen (Inst), GlaxoSmithKline (Inst)
Travel, Accommodations, Expenses: Janssen Oncology, Genesis Pharma, Takeda, Pfizer
Divaya Bhutani
Consulting or Advisory Role: Sanofi
Research Funding: Sanofi (Inst)
Giada Bianchi
Stock and Other Ownership Interests: Pfizer (I)
Honoraria: Pfizer, Alexion/AstraZeneca, Prothena, Janssen
Consulting or Advisory Role: Alexion/AstraZeneca, Prothena
Research Funding: Pfizer, Alexion Pharmaceuticals, Janssen
Travel, Accommodations, Expenses: Prothena, Pfizer
Uncompensated Relationships: Protego Biopharma
Victor H. Jimenez-Zepeda
Honoraria: J & J, GlaxoSmithKline
Research Funding: Myeloma Canada
Suzanne Lentzsch
This author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.
Honoraria: PER, Peerview, IDEOlogy Health
Consulting or Advisory Role: Janssen, GlaxoSmithKline, Pfizer, BMS, Sanofi, Alexion Pharmaceuticals, Kite, a Gilead company, AstraZeneca, Regeneron
Speakers' Bureau: Leukemia, Lymphoma and Myeloma, Springer Nature
Research Funding: Sanofi
Patents, Royalties, Other Intellectual Property: Patent 11-1F4 mAb for use in AL Amyloidosis
Travel, Accommodations, Expenses: Regeneron
Alexander Carpinteiro
Consulting or Advisory Role: Johnson & Johnson/Janssen, Johnson & Johnson/Janssen, Alexion Pharmaceuticals, Sanofi, Alexion Pharmaceuticals
Speakers' Bureau: Bayer/Vital, Johnson & Johnson/Janssen, Johnson & Johnson/Janssen, Johnson & Johnson/Janssen, Alexion Pharmaceuticals
Travel, Accommodations, Expenses: Johnson & Johnson/Janssen
Eugene Scott Swenson
Employment: Alexion Pharmaceuticals
Stock and Other Ownership Interests: Alexion Pharmaceuticals
Patents, Royalties, Other Intellectual Property: Patent application for method of use for anselamimab in kappa light chain amyloidosis (Inst)
Travel, Accommodations, Expenses: Alexion Pharmaceuticals
Zilehuma Khan
Employment: Alexion Pharmaceuticals
Julia Catini
Employment: Alexion Pharmaceuticals
Stock and Other Ownership Interests: Alexion Pharmaceuticals
Travel, Accommodations, Expenses: Alexion Pharmaceuticals
Hrishikesh Kulkarni
Employment: Alexion Pharmaceuticals
Stock and Other Ownership Interests: Alexion Pharmaceuticals
Brian Meltzer
Employment: Alexion Pharmaceuticals
Stock and Other Ownership Interests: Alexion Pharmaceuticals
Stephen Lake
Employment: AstraZeneca
Stock and Other Ownership Interests: AstraZeneca
Michaela Liedtke
Consulting or Advisory Role: Jazz Pharmaceuticals, Sanofi, AstraZeneca, Alexion Pharmaceuticals, Prothena, Arcellx, Lyell Immunopharma, Bristol Myers Squibb, Opna Bio
Uncompensated Relationships: Nexcella
No other potential conflicts of interest were reported.
SUPPORT
Supported by Alexion, AstraZeneca Rare Disease. The Alexion clinical team engaged with key investigators to design and conduct the study, analyze the results, and develop the reports.
CLINICAL TRIAL INFORMATION
NCT04512235 (August 12, 2020) and NCT04504825 (August 5, 2020)
Contributor Information
for the CARES Investigators:
CARES Investigators, Stephen Bek Ngie Ting, Peter Norman Mollee, Hermine Agis, Irene Strassl, Nathalie Meuleman, Michel Delforge, Victor Jimenez Zepeda, Shuyang Zhang, Xin Du, Jianan Wang, Honglan Qian, Chunyan Sun, Honglan Qian, Chunyan Sun, Frantisek Sedlak, Arnaud Jaccard, Karim Belhadj, Bertrand Arnulf, Lionel Karlin, Margaret Macro, Jean-Marc Schiano De Colella, Anne-Marie Stoppa, Frank Bridoux, Thomas Chalopin, Jean-Francois Viallard, Antoine Huart, Alexander Carpinteiro, Roland Fenk, Timon Hansen, Vera Girke, Axel Nogai, Efstathios Kastritis, Argiris (Anargyros) Symeonidis, Moshe Gatt, Noa Lavi, Hila Magen, Giovanni Palladini, Ombretta Annibali, Fabrizio Pane, Gabriele Buda, Tadao Ishida, Kenshi Suzuki, Shinsuke Iida, Takayuki Ikezoe, Krzysztof Jamroziak, Jamin Byun, Youngil Koh, Kihyun Kim, Ramon Lecumberri Villamediana, Maria Teresa Cibeira Lopez, Irene Romera Martinez, Rafael F. Duarte, Rafael Rios, Isabel Angela Krsnik Castello, Maria Esther Gonzalez Garcia, Eusebio Narciso Martin Chacon, Javier Alberto Rojas Martinez, Ashutosh Wechalekar, Jason Valent, Michaela Liedtke, Michael A. Rosenzweig, Alfred Chung, Sandy Wong, Naresh Bumma, Divaya Bhutani, Giada Bianchi, Raymond Comenzo, Mahmoud Gaballa, Hans C. Lee, Gregory P. Kaufman, Eva Medvedova, Frank Passero, Keith Stockerl-Goldstein, Adam Waxman, Vaishali Sanchorawala, Anita D'Souza, Andrew Cowan, Sarah Lee, Edward Libby, Angela Dispenzieri, Amandeep Godara, Tibor Kovacsovics, Salyka M. Sengsayadeth, Stacey Ann Goodman, and Chakra Chaulagain
Supplementary Materials
Protocols
DATA SHARING STATEMENT
A data sharing statement provided by the authors is available with this article at DOI https://doi.org/10.1200/JCO-26-00755. Alexion, AstraZeneca Rare Disease will consider requests for disclosure of clinical study patient-level data, provided that patient privacy is assured through methods like data deidentification, pseudonymization, or anonymization (as required by applicable law) and that such disclosure was included in the relevant study informed consent form or similar documentation. Qualified academic investigators may request patient-level clinical data and supporting documents (statistical analysis plan and protocol) pertaining to Alexion-sponsored studies. Further details regarding data availability and instructions for requesting information are available in the Alexion Clinical Trials Disclosure and Transparency Policy at https://www.alexionclinicaltrialtransparency.com/data-requests/.
AUTHOR CONTRIBUTIONS
Conception and design: Ashutosh D. Wechalekar, Angela Dispenzieri, Vaishali Sanchorawala, Victor H. Jimenez-Zepeda, Suzanne Lentzsch, Julia Catini, Hrishikesh Kulkarni, Brian Meltzer, Stephen Lake, Michaela Liedtke
Financial support: Julia Catini, Stephen Lake
Administrative support: Julia Catini
Provision of study materials or patients: Angela Dispenzieri, Vaishali Sanchorawala, Efstathios Kastritis, Giada Bianchi, Suzanne Lentzsch, Alexander Carpinteiro, Michaela Liedtke
Collection and assembly of data: Ashutosh D. Wechalekar, Angela Dispenzieri, Vaishali Sanchorawala, Efstathios Kastritis, Divaya Bhutani, Giada Bianchi, Victor H. Jimenez-Zepeda, Kenshi Suzuki, Antoine Huart, Eugene Scott Swenson, Julia Catini, Hrishikesh Kulkarni, Stephen Lake, Michaela Liedtke
Data analysis and interpretation: Ashutosh D. Wechalekar, Angela Dispenzieri, Vaishali Sanchorawala, Efstathios Kastritis, Victor H. Jimenez-Zepeda, Suzanne Lentzsch, Alexander Carpinteiro, Eugene Scott Swenson, Zilehuma Khan, Julia Catini, Hrishikesh Kulkarni, Brian Meltzer, Stephen Lake
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Ashutosh D. Wechalekar
Honoraria: Janssen-Cilag, Prothena, Alexion Pharmaceuticals
Consulting or Advisory Role: GlaxoSmithKline, Alexion Pharmaceuticals, ATTRALUS
Travel, Accommodations, Expenses: Janssen, AstraZeneca
Angela Dispenzieri
Research Funding: Celgene (Inst), Janssen Oncology (Inst), Pfizer (Inst), Takeda (Inst), Alexion Pharmaceuticals (Inst), AbbVie (Inst)
Vaishali Sanchorawala
Honoraria: Janssen, Prothena, Prothena, Gate Bioscience, AbbVie, GlaxoSmithKline, Eidos Therapeutics, Alexion Pharmaceuticals
Consulting or Advisory Role: Proclara, Caelum Biosciences, Janssen Research & Development, AbbVie, Regeneron, Protego Biopharma
Research Funding: Takeda (Inst), Celgene (Inst), Prothena (Inst), Janssen (Inst), Oncopeptides (Inst), Caelum Biosciences (Inst), Karyopharm Therapeutics (Inst), Immix BioPharma (Inst), Immix BioPharma (Inst)
Efstathios Kastritis
Honoraria: Genesis Pharma, Janssen Oncology, Takeda, Prothena, Pfizer, GlaxoSmithKline
Consulting or Advisory Role: Janssen Oncology, Takeda, Genesis Pharma, Prothena, Pfizer
Research Funding: Janssen Oncology (Inst), Amgen (Inst), GlaxoSmithKline (Inst)
Travel, Accommodations, Expenses: Janssen Oncology, Genesis Pharma, Takeda, Pfizer
Divaya Bhutani
Consulting or Advisory Role: Sanofi
Research Funding: Sanofi (Inst)
Giada Bianchi
Stock and Other Ownership Interests: Pfizer (I)
Honoraria: Pfizer, Alexion/AstraZeneca, Prothena, Janssen
Consulting or Advisory Role: Alexion/AstraZeneca, Prothena
Research Funding: Pfizer, Alexion Pharmaceuticals, Janssen
Travel, Accommodations, Expenses: Prothena, Pfizer
Uncompensated Relationships: Protego Biopharma
Victor H. Jimenez-Zepeda
Honoraria: J & J, GlaxoSmithKline
Research Funding: Myeloma Canada
Suzanne Lentzsch
This author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.
Honoraria: PER, Peerview, IDEOlogy Health
Consulting or Advisory Role: Janssen, GlaxoSmithKline, Pfizer, BMS, Sanofi, Alexion Pharmaceuticals, Kite, a Gilead company, AstraZeneca, Regeneron
Speakers' Bureau: Leukemia, Lymphoma and Myeloma, Springer Nature
Research Funding: Sanofi
Patents, Royalties, Other Intellectual Property: Patent 11-1F4 mAb for use in AL Amyloidosis
Travel, Accommodations, Expenses: Regeneron
Alexander Carpinteiro
Consulting or Advisory Role: Johnson & Johnson/Janssen, Johnson & Johnson/Janssen, Alexion Pharmaceuticals, Sanofi, Alexion Pharmaceuticals
Speakers' Bureau: Bayer/Vital, Johnson & Johnson/Janssen, Johnson & Johnson/Janssen, Johnson & Johnson/Janssen, Alexion Pharmaceuticals
Travel, Accommodations, Expenses: Johnson & Johnson/Janssen
Eugene Scott Swenson
Employment: Alexion Pharmaceuticals
Stock and Other Ownership Interests: Alexion Pharmaceuticals
Patents, Royalties, Other Intellectual Property: Patent application for method of use for anselamimab in kappa light chain amyloidosis (Inst)
Travel, Accommodations, Expenses: Alexion Pharmaceuticals
Zilehuma Khan
Employment: Alexion Pharmaceuticals
Julia Catini
Employment: Alexion Pharmaceuticals
Stock and Other Ownership Interests: Alexion Pharmaceuticals
Travel, Accommodations, Expenses: Alexion Pharmaceuticals
Hrishikesh Kulkarni
Employment: Alexion Pharmaceuticals
Stock and Other Ownership Interests: Alexion Pharmaceuticals
Brian Meltzer
Employment: Alexion Pharmaceuticals
Stock and Other Ownership Interests: Alexion Pharmaceuticals
Stephen Lake
Employment: AstraZeneca
Stock and Other Ownership Interests: AstraZeneca
Michaela Liedtke
Consulting or Advisory Role: Jazz Pharmaceuticals, Sanofi, AstraZeneca, Alexion Pharmaceuticals, Prothena, Arcellx, Lyell Immunopharma, Bristol Myers Squibb, Opna Bio
Uncompensated Relationships: Nexcella
No other potential conflicts of interest were reported.
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Data Availability Statement
A data sharing statement provided by the authors is available with this article at DOI https://doi.org/10.1200/JCO-26-00755. Alexion, AstraZeneca Rare Disease will consider requests for disclosure of clinical study patient-level data, provided that patient privacy is assured through methods like data deidentification, pseudonymization, or anonymization (as required by applicable law) and that such disclosure was included in the relevant study informed consent form or similar documentation. Qualified academic investigators may request patient-level clinical data and supporting documents (statistical analysis plan and protocol) pertaining to Alexion-sponsored studies. Further details regarding data availability and instructions for requesting information are available in the Alexion Clinical Trials Disclosure and Transparency Policy at https://www.alexionclinicaltrialtransparency.com/data-requests/.