Abstract
The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic hematopoietic cell transplant (allo-HCT) in systemic R/R ALCL are not available. Using CIBMTR database, we evaluated outcomes of 182 adults (≥18years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. Median follow-up of survivors was 62 months (range:3-148). 1-year NRM was 18%. The 5-year REL, PFS and OS were 32%, 41% and 56% respectively. On multivariable regression analysis African American race (hazard ratio [HR]=2.7, 95%CI=1.6-4.8, p<0.001) and refractory disease at allo-HCT (HR=3.2, 95%CI=1.6-6.2, p<0.001) were predictive of inferior OS. Similarly, African American race (HR=2.1, 95%CI=1.3-3.4, p=0.003), other minority race (HR=2.5, 95%CI=1.2-5.3, p=0.02) and refractory disease (HR=2.2, 95%CI=1.2-4.3, p=0.01) were predictive of inferior PFS. These data, demonstrate that allo-HCT can result in durable disease control in a sizable proportion of R/R ALCL patients. Refractory disease and racial minority status predicted inferior allo-HCT outcomes. Whether the inferior outcomes of racial minorities with R/R ALCL post allo-HCT are driven by differences in disease biology or disparities in post allo-HCT care or both requires further investigation.
INTRODUCTION:
Anaplastic large cell lymphoma (ALCL) is a CD30+ aggressive non-Hodgkin lymphoma (NHL) of T-cell/null-cell lineage which comprises about 2% of all NHLs in adults.1,2 Systemic ALCL is divided based on the presence or absence of rearrangements involving the anaplastic lymphoma kinase (ALK) gene into ALK positive (ALK+) and ALK negative (ALK−) variants, with the latter subtype associated with overall inferior prognosis (5 years overall survival (OS) 70% vs 49%).2-6
Addition of brentuximab vedotin (BV), a CD30 targeting antibody drug conjugate (ADC), to frontline anthracycline containing chemotherapy regimens has improved the outcomes in patients with CD30+ ALCL in recent years.7 Although autologous hematopoietic cell transplantation (auto-HCT) consolidation is offered to eligible patients with ALCL in first remission (particularly in the ALK negative subset), its role in the upfront setting remains controversial.8 While limited data suggest some benefit of ALK inhibitors (e.g. crizotinib and certinib) in relapsed/refractory (R/R) ALCL,9-11 generally the prognosis of patients failing first-line modern therapies remains poor.12
Adoptive immunotherapy in the form of allogeneic (allo-) HCT is a potentially curative treatment for patients with select R/R T-cell lymphomas.13-15 In fact, with the recent decreased utilization of allo-HCT in diffuse large B-cell lymphoma, T-cell NHL has now become the most common indication of allografting for lymphomas in the U.S.14-16 However, the role of allo-HCT in R/R ALCL is not well defined. Studies assessing its role are either limited by sample size or by the pooling together of different subtypes of T-cell lymphomas.17,18 Therefore, we evaluated the outcomes of allo-HCT in patients with ALCL using the observational database of the Center for International Blood and Marrow Transplant Research (CIBMTR).
METHODS
Data source
The CIBMTR is a working group comprised of over 380 transplantation centers worldwide that provide data regarding HCT to a statistical center at the Medical College of Wisconsin (MCW). On-site audits ensure compliance of participating transplant centers in reporting all transplantations consecutively. Additionally, quality of data is further augmented through computerized affirmation of discrepancies, physicians’ review of submitted data, and on-site audits of participating centers. Observational studies are conducted by the CIBMTR in compliance with all pertinent federal regulations with regards to protection of human research participants. All patients included in this analysis have provided written consent for research. The Institutional Review Board of MCW and the National Marrow Donor Program have approved this study.
Patients
Adult patients (age ≥18 years) diagnosed with systemic ALCL who underwent allo-HCT between 2008 and 2019 were included in this analysis. Eligible donors included haploidentical donors who received post-transplant cyclophosphamide (ptCY), HLA-identical sibling donors and unrelated donors (MUD) matched at the allele-level at HLA-A, HLA-B, HLA-C and HLA-DRB1 and received calcineurin inhibitor (CNI)-based graft-versus-host disease (GVHD) prophylaxis. Patients who received a haploidentical HCT and did not receive ptCY based GVHD prophylaxis, those with data missing for conditioning intensity and those who received ex-vivo T cell depletion were excluded. Systemic ALCL patients receiving an allo-HCT in first complete remission after only one prior line of systemic therapy (N=9) were also excluded.
Definitions and endpoints
Disease response to last line of therapy at the time before allo-HCT was defined using the International Working Group criteria.19,20 Chemo-refractory disease was defined as patients no having achieved a complete (CR) or partial response (PR) at the time of allo-HCT. The primary endpoint was OS. Death from any cause was considered an event. For progression-free survival (PFS), a patient’s disease was considered a treatment failure at the time of progression/relapse or death from any cause. Patients alive without evidence of disease relapse or progression were censored at last follow-up. Secondary outcomes included non-relapse mortality (NRM) and progression/relapse. NRM was defined as death without evidence of prior lymphoma progression/relapse; relapse was considered a competing risk. Progression/relapse was defined as progressive lymphoma after HCT or lymphoma recurrence after a CR; NRM was considered a competing risk. Acute GVHD and chronic GVHD were graded using established clinical criteria.21,22 Neutrophil recovery was defined as the first of 3 successive days with ANC ≥500/μL after post-transplantation nadir. Platelet recovery was defined as the first of 3 consecutive days with platelet count ≥ 20,000/μL, without platelet transfusion for 7 consecutive days. For neutrophil and platelet recovery, death without the event was considered a competing risk.
Statistical analysis
Baseline characteristics of the study population were described using descriptive statistics. The Cox model and the Kaplan-Meier estimator were used for OS and PFS. The proportional cause-specific hazards model and the cumulative incidence function were used for GVHD, relapse and NRM to account for competing risks.23 The proportional hazards assumption for the regression model was tested by examining a time-varying effect for each risk factor and each outcome. A forward stepwise selection was used to identify significant variables at a significance level 0.05. Variables tested in the regression models included patient-related variables including patient’s age, sex, race, Karnofsky performance status (KPS), HCT comorbidity index, disease-related characteristics including ALK status, history of auto-HCT and disease status at the time of allo-HCT, as well as transplant-related factors including donor type, graft type, conditioning intensity, GVHD prophylaxis and year of allografting. Interactions among significant factors were examined for each outcome. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC).
RESULTS
Baseline characteristics:
A total of 182 patients reported to the CIBMTR with R/R systemic ALCL and undergoing allo-HCT between 2008-2019 were included in this analysis. Table 1 shows the baseline characteristics. The median age of patients was 47 years (range= 18-76 years). Median time from ALCL diagnosis to allo-HCT was 20 months (range=6-208 months) and median follow-up of survivors was 62 months (range=3-148 months). Most patients were of Caucasian race (N=128; 70%) followed by African-American race (N=27; 15%). Median prior lines of therapy were 3 (range= 2-5). One hundred and sixty-seven patients (92%) had chemosensitive disease at the time of allo-HCT. Majority of the patients received reduced-intensity/non-myeloablative conditioning (RIC/NMA) (N=117; 65%) and most common donor source was HLA identical sibling (N=95; 52%). In terms of ALK status, 23% (n=42) were ALK+ and 21% (n=38) ALK−. Of note ALK status was not captured in the CIBMTR registry forms prior to 2013(N=102). Pre transplant BV exposure data were not captured in majority of the patients (93%).
Table 1:
Baseline characteristics
| Characteristics | N=182 (%) |
|---|---|
| Age, median (range), years | 47 (18-76) |
| Age ≥ 60 | 25 (14) |
| Female sex | 69 (38) |
| Patient race - no. (%) | |
| White or Caucasian | 128 (70) |
| Black or African American | 27 (15) |
| Other1 | 12 (7) |
| Missing | 15 (8) |
| Karnofsky performance score ≥ 90 | 109 (60) |
| Disease status - no. (%) | |
| CR | 113 (62) |
| PR | 54 (30) |
| Resistant | 14 (8) |
| Unknown | 1 (1) |
| ALK status positive2 | 42 (23) |
| Peripheral blood stem cells as graft type - no. (%) | 154 (85) |
| Conditioning intensity - no. (%) | |
| Myeloablative | 65 (36) |
| RIC/NMA | 117 (65) |
| HCT-CI ≥3 | 61 (34) |
| Median lines of prior therapy (range) | 3 (2-5) |
| Donor Type - no. (%) | |
| HLA identical sibling | 95 (52) |
| Haploidentical donor | 32 (18) |
| Match unrelated donor | 55 (30) |
| GVHD prophylaxis - no. (%) | |
| ptCY ± other(s) | 26 (14) |
| CNI +/− others | 156 (86) |
| Prior auto-HCT | 66 (36) |
Other race: 11 Asian; 1 Native Hawaiian or other Pacific Islander;
ALK status not collected by CIBMTR before 2013 in 103 (56%)
Abbreviations:
CR, complete response; PR, partial response; RIC/NMA, reduced intensity or non-myeloablative conditioning; HCT-CI, hematopoietic cell transplantation-specific comorbidity index; GVHD, graft-versus-host-disease; ptCY, post-transplant cyclophosphamide; CNI, calcineurin inhibitor; Auto-HCT, autologous hematopoietic cell transplant
Outcomes:
i. Univariate outcomes:
The 1-month cumulative incidence of neutrophil recovery was 95% (95%CI= 91-97%), while 100-day cumulative incidence of platelet recovery was 91% (95%CI= 86-95%). The cumulative incidence of grade 2-4 and severe (grade 3-4) acute GVHD at 6 months was 33% (95%CI= 26-44%) and 13% (95%CI= 8-19%) respectively, while the rate of chronic GVHD at 1-year was 48% (95%CI= 41-56%) (Table 2). The 1-year GVHD-free, relapse-free survival (GRFS) was 47% (95%CI=40-55%).
Table 2:
Outcomes of ALCL after allo-HCT
| Outcomes | Prob (95% CI) |
|---|---|
| Neutrophil recovery at 1-month | 95 (91-97)% |
| Platelet recovery at 100-day | 91 (86-95)% |
| Grade 2-4 acute GVHD at 6 months | 33 (26-41)% |
| Grade 3-4 acute GVHD at 6 months | 13 (8-19)% |
| Chronic GVHD at 1-year | 48 (41-56)% |
| Non-relapse mortality | |
| At 1-year | 18 (12-24)% |
| At 5-year | 27 (20-34)% |
| Relapse | |
| At 1-year | 28 (22-35)% |
| At 5-year | 32 (25-39)% |
| Progression-free survival | |
| At 1-year | 55 (47-62)% |
| At 5-year | 41 (34-49)% |
| GVHD-free, relapse-free survival | |
| At 1-year | 47 (40-55)% |
| At 5-year | 36 (28-44)% |
| Overall survival | |
| At 1-year | 72 (65-78)% |
| At 5-year | 56 (49-64)% |
Abbreviations:
GVHD, graft-versus-host-disease.
The 1-year cumulative incidence of NRM was 18% (95%CI=12-24%) (Table 2. Figure 1A). The 5-year rates of relapse/progression, PFS and OS were 32%, 41% and 56%, respectively (Table 2, Figure 1B-D). There were 77 reported deaths. The most common cause of death was relapsed disease (N=32; 42%), followed by GVHD (N=15; 19%) and infections (N=12; 16%).
Figure 1:
Allogeneic HCT outcomes for ALCL A. Progression-Free Survival B. Overall Survival 1C Non-Relapse Mortality D. Relapse at 1-year and 5-years
On planned subgroup analysis, CR at the time of allo-HCT was associated with better 5-year OS and PFS (67% and 53%) compared with patients with PR (48% and 28%) or resistant disease (14% and 14%) (for details please see Table 3 and Figure 2). In addition, the conditioning regimen intensity had no impact on NRM, relapse/progression, PFS and OS (details in Supplemental Table 1S and Figure 1S).
Table 3.
Impact of Remission Status on HCT outcomes
| CR (N=113) | PR (N=54) | Resistant(N=14) | |||||
|---|---|---|---|---|---|---|---|
| Outcomes | N | Prob (95% CI) | N | Prob (95% CI) | N | Prob (95% CI) | Overall P Value |
| Non-relapse mortality | 109 | 53 | 14 | 0.09 | |||
| 1-year | 15 (9-22)% | 17 (8-28)% | 36 (12-64)% | ||||
| 5-year | 22 (15-31)% | 27 (16-40)% | 50 (23-77)% | ||||
| Relapse | 109 | 53 | 14 | 0.02 | |||
| 1-year | 21 (14-30)% | 40 (27-53)% | 36 (13-63)% | ||||
| 5-year | 25 (17-34)% | 45 (32-59)% | 36 (13-63)% | ||||
| Progression-free survival | 109 | 53 | 14 | <0.001 | |||
| 1-year | 64 (54-73)% | 43 (31-57)% | 29 (9-54)% | ||||
| 5-year | 53 (43-62)% | 28 (16-40)% | 14 (2-37)% | ||||
| Overall survival | 113 | 54 | 14 | <0.001 | |||
| 1-year | 79 (71-86)% | 67 (54-79)% | 36 (14-62)% | ||||
| 5-year | 67 (57-76)% | 48 (35-62)% | 14 (2-37)% | ||||
Figure 2:
Effect of Disease status on transplant outcomes
A. Non-Relapse Mortality, B. Relapse, C. Progression-Free Survival and D. Overall Survival
ii. Multivariable Regression Analysis
Multivariable regression analysis was run to evaluate predictors of allo-HCT outcomes in ALCL. African American race was associated with significantly higher mortality risk (hazard ratio (HR)= 2.79; 95%CI= 1.61-4.84, p=0.0003), inferior PFS (HR= 2.11; 95%CI= 1.29-3.47, p=0.003) and higher NRM (HR= 3.79; 95%CI= 1.95-7.38, p<0.0001) compared to Caucasians (Table 4). Although there was no difference in OS and NRM, non-white/non-black race was associated with inferior PFS (HR 2.5; 95%CI 1.18-5.30, p=0.02) and higher relapse rates (HR= 3.16; 95%CI= 1.3-7.65, p=0.01).
Table 4:
Multivariable regression analysis
| HR (95% CI) | Overall p value | ||
|---|---|---|---|
| Relapse | |||
| Race | |||
| Caucasian | Reference | 0.049 | |
| African American | 1.27(0.61-2.68) | ||
| Others | 3.16 (1.3-7.65) | ||
| Missing | 1.83 (0.8-4.17) | ||
| Disease status | |||
| CR | Reference | 0.04 | |
| PR | 1.99 (1.15-3.46) | ||
| Resistant | 1.72(0.66-4.52) | ||
| Prior auto-HCT | |||
| No | Reference | 0.01 | |
| Yes | 0.40 (0.20-0.77) | ||
| Non-relapse mortality | |||
| Race | |||
| Caucasian | Reference | 0.002 | |
| African American | 3.79 (1.95-7.38) | ||
| Others | 1.38 (0.33-5.85) | ||
| Missing | 1.55 (0.46-5.17) | ||
| Disease status | |||
| CR | Reference | 0.03 | |
| PR | 1.45(0.75-2.83) | ||
| Resistant | 3.13 (1.33-7.39) | ||
| Progression Free Survival | |||
| Race | |||
| Caucasian | Reference | 0.004 | |
| African American | 2.11(1.29-3.47) | ||
| Others | 2.50 (1.18-5.30) | ||
| Missing | 1.74 (0.88-3.43) | ||
| Disease status | |||
| CR | Reference | 0.01 | |
| PR | 1.72(1.12-2.63) | ||
| Resistant | 2.28 (1.20-4.33) | ||
| Prior auto-HCT | |||
| No | Reference | 0.01 | |
| Yes | 0.51 (0.31-0.82) | ||
| Overall Survival | |||
| Race | |||
| Caucasian | Reference | 0.004 | |
| African American | 2.79 (1.61-4.84) | ||
| Others | 1.54 (0.60-3.92) | ||
| Missing | 1.58 (0.70-3.57) | ||
| Disease status | |||
| CR | Reference | 0.003 | |
| PR | 1.39 (0.83-2.31) | ||
| Resistant | 3.19 (1.63-6.24) | ||
| Prior auto-HCT | |||
| No | Reference | 0.04 | |
| Yes | 0.54 (0.3-0.97) | ||
Abbreviations:
Auto-HCT, autologous hematopoietic cell transplant; CR:Complete response; PR,Partial response; auto-HCT=Autologous transplant
Resistant disease at the time of allo-HCT was also associated with an inferior OS (HR=3.19; 95%CI= 1.63-6.24, p=0.001) and PFS (HR= 2.28; 95%CI= 1.12-4.33, p=0.01), while PR at the time of allo-HCT was associated with an inferior PFS (HR= 1.72; 95%CI= 1.12-2.63, p=0.01) and higher relapse rates (HR= 1.99; 95%CI= 1.15-3.46, p=0.01), but not inferior OS (HR= 1.39 95%CI=0.83-2.31, p=0.21). For details, please see Table 4.
iii. Baseline characteristics of minority patients
To further explore the worse outcomes of racial minorities seen on the multivariable regression analysis, the baseline characteristics were examined according to patient race (Caucasian vs. African Americans vs. Others) (Supplemental Table 2S). There were no significant differences between the three cohorts in terms of median patient age, sex, remission status at the time of allo-HCT, graft source, conditioning intensity, HCT comorbidity index, number of prior lines of therapies or time from diagnosis to allo-HCT. However, significantly fewer African American patients had a KPS of 90 or higher at the time of allo-HCT (30%), compared to Caucasian patients (63%) and other races (67%; p=0.02) and a lower number of African American patients (19%) had undergone an auto-HCT prior to allo-HCT versus Caucasian patients (40%) and other races (58%; p=0.04). HLA-identical sibling donors was the most common (44%) and MUD (15%) was the least common donor source among African Americans (p<0.01).
DISCUSSION
Large studies evaluating the role of allo-HCT in R/R ALCL are not available. In this retrospective analysis using CIMBTR registry, we report outcomes of 182 ALCL patients who received an allo-HCT for relapsed or refractory disease. This is largest study of allografting for ALCL which included patients with heavily pretreated disease (median 3 prior lines of therapy). Overall, a sizeable subset of patients had durable disease control with 5-year PFS and OS of 41% and 56%, respectively. Notably, survival outcomes were significantly impacted by patient race, with minorities experiencing inferior survival outcomes.
There are limited data available for outcomes of allo-HCT in ALCL. In a study of 52 patients with peripheral T cell lymphoma (PTCL) including 11 patients with ALCL, the OS and PFS were 50% and 40%, respectively.18 Le Gouill et al. reported allo-HCT outcomes in 77 patients with aggressive T-cell lymphoma including 27 cases of ALCL. The 5-year OS and event free survival (EFS) rates were 57% and 53%, respectively.24 While ALK status is a known prognostic factor for ALCL,4,6 among patients with available data (N=79), ALK status was not found to be predictive of allo-HCT outcomes in our analysis. Of note, ALK status was not collected by CIBMTR before 2013, hence this information was not available on 103 (56%) patients, and this is certainly a limitation of this analysis. Remission status at the time of transplant was a predictor of transplant outcomes in the current study. Relative to patients in CR, those with refractory disease or PR had inferior PFS, while refractory patients also had inferior OS. These observations are consistent with previous studies of allo-HCT in PTCLs.18,24-26 In a study by Domingo-Domenech et al., uncontrolled disease at the time of allo-HCT led to inferior OS (HR 0.25 (0.07-0.83), PFS (HR= 0.22 (95%CI=0.09-0.55) and higher risk of relapse (HR= 0.27 (95%CI=0.11-0.74) on univariate analysis.
BV administration prior to allo-HCT in R/R ALCL has neither been associated with any safety concerns based on prior analyses albeit with limited sample size, nor shown to impact allo-HCT outcomes in a study by Domingo-Domenech et al.26-30 In our study, 169 (93%) of cases were reported on Transplant Essential Data (TED) track which does not capture the types of therapies administered before allo-HCT. Among the 13 cases reported on the detailed Comprehensive Report Forms (CRF) track, 10 patients had prior BV (77%). Since this information was available only on a very small subset, we could not evaluate BV’s impact on allo-HCT outcomes, and this represents a limitation of this report. However, since BV was approved for R/R ALCL in 2011 and as first-line in 2018, it is possible that most patients in the study had prior BV exposure.
A noteworthy finding in our study was the adverse prognostic effect of recipient race, with significantly inferior outcomes following allo-HCT in African Americans (worse NRM, PFS and OS) and non-African American/non-Caucasian races (higher relapse and inferior PFS). While there were some differences in the baseline characteristics across patients when stratified by race (e.g. African American patients had lower KPS, less frequent history of auto-HCT, or grafts from MUDs), the multivariable regression analysis (adjusted for these variables) confirmed the independent prognostic significance of patient race. The outcomes of ALCL, were worse in African American, Hispanic white and American Indian/Alaskan native patients (even among studies not focusing on transplantation).31-33 In a recent analysis of the Surveillance, Epidemiology, and End Results (SEER) public data from 2000 to 2010, the OS was worse in African American compared to Caucasians with PTCL.34 This was redemonstrated in patients with ALK+ ALCL with a 5-year OS of 37.7% in African Americans and 49.7% in Caucasians.35 Of note the proportion of African American patients in the SEER analysis35 (~15%) is identical to the proportion of transplant in our current report. The underlying reasons for this are poorly understood and may potentially be related to biological differences between races such as variations in pharmacokinetics or pharmacodynamics of drugs, genomic variations of the tumors, socioeconomic status and inequality of health care delivery. Additionally, the absolute numbers of patients from minority groups are small which could impact analysis. Further studies are needed to explore the underlying reasons for these differences and improve outcomes.
In our study we did not find any difference in outcomes between myeloablative conditioning (MAC) vs RIC/NMA. The OS, PFS, NRM and relapse were similar in between the two groups. This is similar to a previous study in T-cell NHL (not limited to ALCL) from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) of 285 patients who underwent allo-HCT for PTCL.36 In addition, Savani et al. reported similar findings in a recently published CIBMTR analysis. The 5-year OS, PFS and NRM were not different in the patients who received RIC/NMA versus those who received MAC while the risk of grade 2-4 GVHD was higher in the MAC cohort.13
This analysis has several limitations. Inherent with large retrospective registry studies, potential patient selection biases and center-specific transplantation practices cannot be excluded. Socioeconomic parameters, highest education level, distance from transplant center, granular aspects of post-transplant care and type of insurance were not available in the majority of patients to investigate further the reasons of less favorable outcomes among minority patients. It is important to point out that since CIBMTR does not capture data on non-transplanted ALCL patients, our observations of less favorable outcomes among minority patients may not be extrapolatable to ALCL in general. In this registry analysis we do not have the granularity of data to confirm if all included patients underwent a positron emission tomography (PET) scan to assess pre HCT remission status. However it is import to point out that prior data have shown that PET scans before allo-HCT are not predictive of PFS or OS.37
In conclusion, this is a large registry-based study of R/R ALCL allo-HCT provided durable disease control in a sizeable subset of patients, particularly those in achieving a CR prior to allo-HCT. Recipient race appears to have an impact on transplant outcomes and the reason for this discrepancy is not readily explained by disease- and transplant-related variables captured in the registry and warrant future investigations.
Supplementary Material
ACKNOWLEDGEMENTS:
The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Inc.; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; Incyte Corporation; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Stemcyte; Takeda Pharma; Vor Biopharma; Xenikos BV.
Footnotes
Disclosure of conflict of interest:
S. Ahmed reports: research funding from SeaGen, Tessa Therapeutics, Merck. Consulting or Advisory role: SeaGen, Tessa Therapeutics
M. Shadman Consulting, Advisory Boards, steering committees or data safety monitoring committees: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys/Incyte, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang Bio, Regeneron, Merck, Fate therapeutics, MEI pharma and Atara Biotherapeutic. Research Funding: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, AbbVie, TG Therapeutics, Beigene, AstraZeneca, Sunesis,Atara Biotherapeutics, Genmab, Morphosys/Incyte.
C. Sauter reports: Consultancy/Advisory boards: Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite/a Gilead Company, Celgene/BMS, Gamida Cell, Karyopharm Therapeutics, GSK; Research Funding: Juno Therapeutics, Celgene/BMS, Bristol-Myers Squibb, Precision Biosciences and Sanofi-Genzyme.
S. Barta reports Consultancy/advisory boards: Acrotech Biopharma, Affimed, Daiichi Sankyo, Kyowa Kirin, SeaGen.
A. Herrera reports: Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Seattle Genetics, Karyopharm, Genentech/Roche, ADC Therapeutics, Tubulis, Takeda, AstraZeneca; Research Funding: Bristol-Myers Squibb (Inst), Genentech/Roche (Inst), Merck (Inst), Seattle Genetics (Inst), ADC Therapeutics (Inst), Gilead/Kite Pharma (Inst).
M. Hamadani reports: Consultancy: Incyte Corporation; ADC Therapeutics; Pharmacyclics, Omeros, Genmab, Morphosys, Kadmon, Kite, Novartis, Abbvie, Legend, Gamida Cell, SeaGen. Speaker’s Bureau: Sanofi Genzyme, AstraZeneca, BeiGene, ADC Therapeutics.
T. Gregory reports: Funding: AbbVie, Amgen, Acetylon, Bluebird, Bristol Myers Squibb, Celgene, Celularity, Constellation, CRISP Therapeutics, CURIS, EMD Serono, Genentech, Glenmark, Janssen, Kesios, Lilly, Novartis, Poseida, Sanofi, Takeda, Teva, and Vivolux
L. Hill reports Consultancy/advisory boards: Incyte
J. Zain reports Consulting or Advisory Role: Seattle Genetics, Secura Bio , Kiyowa Kirin., Daichi Sankyao CRSPR, Myeloid. Research support : Secura Bio, Astra Zeneca,Seatlle Genetics, Myeloid , CRSPR, Daichi Sankyo
M Perales reports honoraria from Abbvie, Allovir, Astellas, Bristol-Myers Squibb, Caribou Biosciences, Celgene, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, OrcaBio, Takeda, and VectivBio AG, Vor Biopharma. He serves on DSMBs for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier, and the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros. He has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.
The other authors reported no conflicts of interest to disclose.
Data sharing statement:
The CIBMTR makes its publication analysis datasets freely available to the public for secondary analysis while safeguarding the privacy of participants and protecting confidential and proprietary data: https://www.cibmtr.org/referencecenter/publist/pubdsdownload.
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Data Availability Statement
The CIBMTR makes its publication analysis datasets freely available to the public for secondary analysis while safeguarding the privacy of participants and protecting confidential and proprietary data: https://www.cibmtr.org/referencecenter/publist/pubdsdownload.