ABSTRACT
First‐line therapy for mantle cell lymphoma (MCL) represents a critical opportunity for clinical benefit via sustained complete response. We conducted a phase 2 multicenter trial in the academic and community cancer research united (ACCRU) network, testing a multitargeted 1st line regimen. CARiBOU (ACCRU‐LY‐1804) employs alternating VR‐CAP and R‐cytarabine with continuous acalabrutinib, in six 21‐day cycles, for previously untreated MCL. The primary endpoint was complete metabolic response (CMR) rate. Secondary endpoints included safety, feasibility of stem cell collection, proportion proceeding to ASCT, and progression‐free (PFS) and overall survival (OS). Peripheral blood measurable residual disease (MRD) was tested using the ClonoSEQ assay (Adaptive Biotechnologies). Of 41 patients enrolled, 39 (95%) responded to therapy, including 37 patients achieving CMR (90%). Two nonresponders discontinued therapy for toxicity early, prior to study‐defined restaging, and received alternate therapy. Undetectable MRD at a 106 threshold was achieved in 26/33 tested patients (79%), and 94% at 105. 18‐month estimated PFS is 79% (95% CI 64%–97%), and OS is 96% (95% CI 88%–100%). Toxicities were primarily hematologic (grade 3 hematologic AE in 32 patients, [78%]). Twelve required platelet transfusions, and one grade 3 bleeding event occurred. Febrile neutropenia occurred in 4 patients, and 6 (14%) experienced SAEs. There were no treatment‐related deaths. CARiBOU is an efficient, highly effective outpatient 1st line MCL regimen, employing intermediate‐dose cytarabine and continuous acalabrutinib for 6 cycles. This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD‐guided decisions on consolidation and maintenance.
Trial Registration: ClinicalTrials.gov identifier: NCT04626791
1. Introduction
Chemoimmunotherapy is the standard of care for fit, historically “transplant‐eligible” patients with newly diagnosed mantle cell lymphoma (MCL). Cytarabine‐based regimens afford high efficacy and eliminate molecular evidence of measurable residual disease (MRD) in most patients, with implications for remission duration and consolidation therapy [1, 2, 3, 4, 5, 6, 7]. Recently, the TRIANGLE and EA4181 studies tested the addition of Bruton's tyrosine kinase inhibition (BTKi) to intensive chemotherapy, leading to excellent outcomes and durable remissions without autologous stem cell transplantation (ASCT) [4, 5]. However, cytarabine combinations impart significant myelotoxicity and risks, and require hospitalization for therapy and intermittent BTKi administration for tolerability. Improvement in efficacy of intensive, MCL‐specific induction therapy—while reducing risk and logistical burden—remains a relevant goal.
Toward this end, we developed the CARiBOU regimen: cytarabine, acalabrutinib, and rituximab integrated with bortezomib‐based outpatient therapy. This regimen follows from our prior data with alternating high‐dose cytarabine (HIDAC) and bortezomib‐based treatment (VR‐CAP) [8]. While this intensified regimen was highly effective (CR 86%), it resulted in predictable myelotoxicity and frequent need for platelet transfusions. CARiBOU represents an evolution of this approach, adding BTKi with acalabrutinib, reducing cytarabine dose, and employing fixed‐duration outpatient therapy. Herein, we report primary efficacy and safety analyses of our prospective trial of 1st line therapy for transplant‐eligible MCL patients in the multicenter ACCRU‐1804 trial (CARiBOU/NCT04626791).
2. Methods
2.1. Patients
Eligible patients were at least 18 years old without prior systemic therapy for MCL, diagnosed by local institutional pathology review, and were eligible for ASCT according to investigator judgment. Prephase corticosteroid therapy (≤ 7 days) was permissible. Adequate organ function, measurable disease, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less were required, as was a platelet count of at least 100 000/mm3 (or at least 75 000/mm3 if due to lymphomatous marrow or spleen involvement). Patients were excluded in case of prior anthracycline over 150 mg/m2, grade 2 or higher peripheral neuropathy, warfarin anticoagulation, active infection or bleeding, known gastrointestinal ulceration unless due to MCL, prior bortezomib or BTKi therapy, or requirement for ongoing use of a strong cytochrome P450 CYP3A4 inhibitor/inducer.
2.2. Treatment and Disease Assessment
CARiBOU (ACCRU‐LY‐1804) employs alternating VR‐CAP and R‐cytarabine with continuous acalabrutinib in six 21‐day cycles. VR‐CAP (cycles 1, 3, and 5) uses bortezomib 1.3 mg/m2 subcutaneously days 1,8, and 15; rituximab 375 mg/m2 day 1; cyclophosphamide 750 mg/m2 day 1; doxorubicin 50 mg/m2 day 1; and prednisone 100 mg PO days 1–5. Cycles 2, 4, and 6 used outpatient rituximab with cytarabine at 3 g/m2 × 2 daily doses for the first 5 patients, after which the dose was reduced to 2 g/m2 × 2 daily doses for all subsequent patients due to thrombocytopenia. Cytarabine doses were given at least 18 h apart on consecutive days. Twice‐weekly monitoring of the complete blood count was required after cytarabine‐containing cycles and weekly during VR‐CAP. Acalabrutinib 100 mg p.o. twice daily was administered continuously for all 6 cycles, but held for grade 4 thrombocytopenia or other clinically significant toxicity. White blood cell growth factors were required with each cycle. Prophylactic antimicrobials were also required for both varicella zoster virus (acyclovir 400–800 mg twice daily) and pneumocystis jirovecii (trimethoprim‐sulfamethaxazole once three times a week, or twice daily 2 days per week, or alternative such as dapsone). These were given continuously during study treatment and discontinued per institutional practice after the end of therapy.
Responses were assessed after 6 cycles using FDG PET/CT for the primary endpoint of complete metabolic response rate (CMR) rate [9]. MRD was assessed in peripheral blood after cycle 3 and at end‐of‐treatment, using the ClonoSEQ assay (Adaptive Biotechnologies), and is reported at 106 and 105 thresholds; uMRD6 denotes absent MRD at the 106 threshold.
Maintenance or consolidation therapy was not protocol‐defined, although CARiBOU was designed for pretransplant induction, and rituximab maintenance post‐transplant was expected as standard‐of‐care therapy. After end‐of‐treatment response assessment, patients underwent protocol‐defined event monitoring for up to 2 years, then additional standard‐of‐care monitoring for relapse and survival.
2.3. Statistical Considerations
The primary endpoint was CMR rate at end of treatment (EOT), defined as a Deauville score of 1–3. Secondary endpoints included safety, feasibility of stem cell collection, proportion proceeding to ASCT, and progression‐free (PFS) and overall survival (OS). A Simon two‐stage design targeted a CMR rate ≥ 70% versus a null rate of 50%, with a total sample size of 39 evaluable patients (maximum 45).
Adverse events (AE) were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5. Progression‐free survival (PFS) counted time from registration until disease progression or death from any cause. Overall survival (OS) reported time from registration until death from any cause.
2.4. Trial Oversight
The study was conducted in accordance with International Council for Harmonization Guidelines and ethical principles of the Declaration of Helsinki. All patients provided written informed consent.
3. Results
3.1. Patient Characteristics
This study accrued 41 total patients from 4 centers between 10/4/21 and 6/5/25 (Patient Disposition, Figure 1). Median age was 61 years with a male predominance (78%). Mantle Cell International Prognostic Index (MIPI) group was intermediate/high in 23 (56%), and elevated Ki67 (30% or higher) in 22 (54%) (Table 1). Among 34 tested, 4 (12%) had TP53 mutations; p53 expression by immunohistochemistry was not consistently performed.
FIGURE 1.
Patient disposition. [Color figure can be viewed at wileyonlinelibrary.com]
TABLE 1.
Patient characteristics.
| Age, median years (range) | 61 (41–73) |
| ≥ 65 years (%) | 13/41 (32%) |
| ≥ 70 years (%) | 4/41 (10%) |
| Sex female (%) | 9 (22%) |
| ECOG performance status, n (%) | |
| 0–1 | 40 (98%) |
| 2 | 1 (2%) |
| Elevated KI67 (> = 30%), n (%) | |
| Yes | 22 (54%) |
| No | 19 (46%) |
| Morphology | |
| Classical/blastoid or pleomorphic/no data, n | 35/1/5 |
| TP53 mutation present, n (%), among 34 tested | 4/34 (12%) |
| Ann Arbor stage, n (%) | |
| III–IV (1 missing) | 37/40 (93%) |
| MIPI risk group, n (%) | |
| Low | 18 (44%) |
| Intermediate | 16 (39%) |
| High | 7 (17%) |
| Time since initial Dx (mo) | |
| N | 41 |
| Median (range) | 21 (2, 95) |
3.2. Treatment Received
39 of 41 patients completed all 6 cycles of protocol therapy. Median relative dose intensity was 95% or greater for each agent.
Acalabrutinib interruptions occurred in 29 patients (for any/all reasons, including omitted doses due to patient error, drug interactions, protocol requirement, toxicity, or planned hold for invasive procedures). Thrombocytopenia led to protocol‐defined hold of acalabrutinib in 16/41 (39%) of patients, almost exclusively during cytarabine nadirs. Median relative dose intensity of acalabrutinib was 95% (mean dose intensity, 92%).
Two patients failed to complete more than 2 cycles of study therapy and were not evaluable for the primary endpoint. Of these, one had a grade 3 hemorrhage from a duodenal ulcer diagnosed 20 days after start of cycle 1, and declined transfusion support. He received alternate therapy (bendamustine, rituximab, and acalabrutinib) and remains free of progression. The other experienced grade 4 febrile neutropenia with hospitalization complicated by thrombocytopenia and thrombotic thrombocytopenic purpura after cycle 2 of therapy; a subsequent bone marrow aspirate and biopsy showed persistent involvement by MCL. This patient recovered and received treatment with lenalidomide with obinutuzumab starting 34 days after the last dose of study therapy and is alive at last follow‐up (more than 18 months after enrollment).
Consolidation and maintenance therapies were not protocol‐specified. While designed in the ASCT era, data have changed rapidly and only 9 patients (23%) underwent ASCT. Among these patients, there were no stem cell collection failures (all collected at least 2 × 106 CD34 cells/kg pt. body weight), and 7 (77%) required 1 day of pheresis.
Rituximab maintenance was administered to 36/39 (92%) of patients who completed all therapy, and BTKi maintenance was employed in 9 (23%), with duration at the discretion of the treating investigator (Figure S2).
3.3. Efficacy
Of 41 patients by intention to treat, the CMR is 90% (95% CI 83%–99%) with an ORR of 95% (95% CI 92%–100%), with two patients who came off study before 2 cycles (and did not receive protocol imaging) scored as nonresponders. Two patients had partial response, although these patients achieved uMRD6 at EOT; FDG avid sites resolved with follow‐up PET imaging (including a single mesenteric node in one case, and spleen/marrow uptake after G‐CSF in another), and both remain in remission.
Of the 34 patients who underwent bone marrow aspirate and biopsy at EOT, 32 (94%) were negative for MCL. The two patients with positive EOT marrows showed low‐level flow cytometry and cyclin D1 positivity (< 1% involvement); MRD6 results were indeterminate and positive in these patients. Among 4 patients with TP53 mutation at baseline, one discontinued therapy early due to toxicity, was scored as a nonresponder as described above, and received alternate therapy. Three other patients with mutated TP53 achieved CR with uMRD6 and none have relapsed during follow‐up; 2 received rituximab maintenance and one received BTK maintenance (only).
3.4. MRD Outcomes
No patient failed baseline ClonoSEQ Identification testing, although only 33 were evaluable with baseline and follow up peripheral blood samples tested. Among these 33, uMRD6 at EOT was achieved in 26 (79%), with 3 (9%) indeterminate results and 4 (12%) positive. At the 105 threshold, 31 (94%) were MRD negative and 2 (6%) were positive at EOT. Only 5 of 32 (16%) of samples tested mid‐therapy (after cycle 3) achieved uMRD6.
3.5. Toxicity
All 41 patients who received at least one dose of protocol‐specified treatment were included in the safety evaluation. Grade 3–4 or higher hematologic AE were observed in 32 (78%) patients and included thrombocytopenia 27 (66%), neutropenia 12 (29%), and anemia 11 (27%) (Table 2). Febrile neutropenia occurred in 4 patients (two grade 3 and two grade 4). Grade 3 non‐hematologic AE occurred in 13 (32%) patients, with vasovagal reaction the only grade 3 AE occurring in more than one (seen in 2 [5%]). Grade 3 atrial fibrillation was observed in 1 patient; no ventricular arrhythmias occurred.
TABLE 2.
Grade 3–5 AE Occurring in > 1 patient, by frequency.
| Grade 3 (%) | Grade 4 (%) | Total (%) | |
|---|---|---|---|
| Thrombocytopenia | 12 | 54 | 66 |
| Neutropenia | 2 | 27 | 29 |
| Anemia | 26 | 0 | 26 |
| Febrile neutropenia | 5 | 5 | 10 |
| Vasovagal reaction | 5 | 0 | 5 |
| Infusion‐related reaction | 5 | 0 | 5 |
Grade 1–2 non‐hematologic AE primarily included rituximab infusion reactions 20 (49%), peripheral neuropathy (all grade 1) in 8 (20%), as well as nausea 8 (19%) and headache in 7 (18%) (Table S1). Infections were infrequent, with grade 1–2 infections in 5 (12%) patients and 4 (10%) instances of oropharyngeal candidiasis; there was only 1 (5%) instance of grade 3 infection (lung infection and sepsis).
Six patients (14%) experienced serious adverse events, primarily febrile neutropenia or infection, and no patient died during or within 100 days of study therapy.
3.6. Risk and Management of Bleeding Events
Platelet transfusions were needed exclusively during cytarabine nadirs, for 12/41 patients (29%) including 5/5 patients treated at the initial cytarabine dose (3 g/m2 × 2 daily doses), versus 7/36 receiving the 2 g/m2 × 2 daily dose. When evaluated per cycle of therapy, 60% (9/15) of cycles with the higher cytarabine dose required platelet transfusion, compared to 9% (9/103) of cycles at 2 g/m2. With twice weekly monitoring and supportive transfusion, clinically significant bleeding events were uncommon: grade 1–2 purpura occurred in 2 (5%), epistaxis in 1 (3%), and 1 (3%) grade 3 gastrointestinal bleed event occurred in a patient newly diagnosed with a duodenal ulcer (diagnosed 20 days after start of study therapy).
3.7. Progression‐Free and Overall Survival
With a median follow‐up of 17 months, 4 patients have relapsed, individually detailed in Table S2. As shown in Figure 2, 18 months estimated PFS is 79% (95% CI 64%–97%). OS is 96% at 18 months (95% CI 88%–100%, Figure 3). Too few relapse events have occurred to identify features predicting adverse PFS with this regimen.
FIGURE 2.
PFS.
FIGURE 3.
OS.
Of the two deaths, one occurred in a 64‐year‐old man who died 370 days from last study therapy due to complications of COVID‐19 while receiving rituximab maintenance. The patient was in remission from MCL and had also received ASCT consolidation. The second death occurred 471 days after last study therapy and was due to progressive MCL in a patient with MYC‐rearranged disease; this patient had also received ASCT consolidation (Figure S1, Swimmer Plot).
4. Discussion
Initiated in 2021, the CARIBOU study followed from our experience with alternating VR‐CAP and HIDAC—a regimen based on randomized data showing superiority of these components over historical RCHOP‐like therapy [3, 8, 10]. The intent of CARIBOU was threefold: to limit chemotherapy toxicity (reduce cytarabine), improve logistics (outpatient therapy, fixed‐duration BTKi), and preserve high CR rates and feasibility of stem cell collection. These aims were met by employing cytarabine 2 g/m2 in two daily doses, limiting transfusional requirements and risk of febrile neutropenia, in an all‐outpatient regimen.
CARiBOU therapy was highly effective with all evaluable patients responding, including a 90% CMR in a study population characterized by intermediate/high risk MIPI in 56%, and elevated proliferation index (Ki67 ≥ 30%) in 54%. High efficacy is an essential feature of first‐line MCL therapy, with excellent published results and ensuing expert consensus guideline support for NORDIC, bendamustine/cytarabine, and TRIANGLE regimens for fit MCL patients [2, 4, 5, 11]. However, combining BTKi with intensive therapies remains challenging as shown in the design of TRIANGLE and ECOG‐ACRIN 4181 studies, which avoided continuous BTKi dosing during cytarabine cycles [4, 5]. While likely limiting toxicity, this approach may limit any additive or synergistic benefit of 1st line BTKi with intensive therapy. By reducing cytarabine dose, we were able to maintain high overall dose intensity of acalabrutinib, even though temporary interruptions of acalabrutinib were required in most (29) patients at some point. Our observed rates of uMRD6 (79%) and uMRD5 (94%) are comparable or superior to other BTKi‐containing induction regimens [4, 5, 7, 12, 13, 14] indicating high efficacy via time‐limited outpatient therapy, completed in under 5 months.
Despite an intermediate cytarabine dose, CARiBOU must still be considered an intensive regimen, requiring twice‐weekly CBC monitoring and protocol‐defined acalabrutinib holds, and associated with grade 4 thrombocytopenia in 55% of patients. During the study, we modified the cytarabine dose to 2 g/m2 for 2 daily doses, leading to a reduction in the proportion of cycles requiring transfusion support from 60% (at 3 g/m2) to 9% at the lower dose. While transfusion support is not described in TRIANGLE, 61% of patients in the chemoimmunotherapy + ibrutinib arm experienced grade 3 or higher thrombocytopenia [4]. Differences in the age of our study patients (median 61 years., vs. 57 in TRIANGLE) as well as eligibility criteria (platelets of at least 75 k/μL if due to MCL, vs. 100 k/μL in TRIANGLE) highlight challenges of cross‐trial comparison. With protocol‐defined monitoring, only 1 high grade bleeding event was observed; this occurred early during cycle 1 after VR‐CAP, from a newly diagnosed duodenal ulcer. Furthermore, we observed no significant renal toxicity, in contrast to the 6% risk of grade 3 or higher acute kidney injury observed in TRIANGLE, which employs platinum chemotherapy [4]. Despite being conducted during the COVID pandemic, infectious adverse events during therapy were mostly low‐grade (grade 1–2 infections 13% excluding thrush). There was no treatment‐related mortality, one grade 3 infection, and 6 of 41 patients experienced an SAE. Overall, we believe the overall safety of CARiBOU is comparable or superior to high‐dose cytarabine regimens. It is also plausible that, by avoiding reliance on bendamustine which leads to severe T‐cell depletion and delayed infectious risk [15], CARiBOU may comprise a safer platform from an infectious risk standpoint, and lower risk to T‐cell fitness (in case subsequent T‐cell based immunotherapies are required) [16]. However, this study only recorded adverse events until 30 days after the last dose of study drug, precluding evaluation for late infectious events.
Limitations of this study include its single‐arm design, small sample size, regimen complexity, and heterogenous maintenance and consolidation therapies. While we demonstrate excellent initial efficacy in this primary efficacy analysis, our median follow‐up is only 17 months; deep initial responses do not guarantee long‐term disease control in MCL. In randomized trials, it appears that BTKi inhibitors may exert their greatest benefit during maintenance therapy, rather than synergistic effects during induction chemoimmunotherapy. In particular, TRIANGLE showed only a slightly improved CR rate and more MRD negativity with ibrutinib during induction, and ECHO showed similar MRD at end of first‐line treatment including acalabrutinib—but more conversation to negative MRD with continued BTKi maintenance [4, 7, 12, 17]. In addition, withdrawal of BTKi therapy in the first‐line setting will lead to relapse in some subsets, especially among high‐risk patients (blastoid/TP53, cytogenetic complexity) [18]. Thus, the primary benefit of BTKi in first‐line treatment may be through suppression of malignant clones via long‐term therapy, instead of deeper initial response. On the other hand, maintenance BTKi exposes patients to infectious risk, and increased mortality risk with ibrutinib as observed in SHINE [19]. Overall, our data cannot define an optimal duration of first‐line BTKi, nor do we imply that time‐limited BTKi combinations are appropriate for all MCL patients. Further studies are needed to optimize BTK maintenance, potentially incorporating depth of response (MRD) as well as disease‐ and patient‐specific factors.
In summary, the CARiBOU is an effective and efficient regimen for 1st line treatment of fit patients with MCL. While much attention has (rightfully) been given to complete replacement of chemoimmunotherapy including for high‐risk MCL [20], optimization of time‐limited, multitargeted regimens and cytarabine dosing remains a valid goal. We believe that the CARiBOU regimen represents an iterative improvement, offering high efficacy and MRD negativity with fixed‐duration BTKi and a potentially improved infectious toxicity profile. This regimen may be applied as induction therapy for fit MCL patients considering MRD‐guided transplant decisions (as per EA41511), for patients intolerant of bendamustine, or as part of an approach akin to the TRIANGLE regimen [4] (with 2 years of BTKi). We acknowledge that CARiBOU's inherent complexity and use of bortezomib may limit its implementation, despite the overall survival benefit demonstrated with VR‐CAP (over R‐CHOP) in older MCL patients [10]. While the future of MCL therapy may be chemotherapy‐free, CARiBOU supports a current role for multitargeted therapy in addressing the known biologic heterogeneity of MCL in a time‐limited, highly effective manner.
Author Contributions
Conception and design: Stephen D. Smith. Provision of study materials or patients: Suchitra Sundaram, Yucai Wang, Ajay K. Gopal, Yifan Pang, Ryan C. Lynch, Edus Warren, Steven Park, Grzegorz Nowakowski. Collection and assembly of data: Sharmila Giri, Andy Ness, Emily Tatoian, Trenton Grossfeld. Manuscript writing: Stephen D. Smtih. Final approval of manuscript: All authors.
Funding
This work was supported by AstraZeneca.
Disclosure
Stephen D. Smith: Research Funding: Astrazeneca, Corvus pharmaceuticals, Viracta Therapeutics, Merck Sharp and Dohme Corp, ADC Therapeutics, Beigene/BeOne, Enterome, Genentech, Incyte Corporation, Kymera, Loxo Oncology, Pfizer Oncology. Consultancy: Beigene, Genentech, Lumanity. Suchitra Sundaram: Research Funding: Lymphoma Research Foundation. Sharmila Giri: None. Andy Ness: None. Yucai Wang: Research funding: Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck, AstraZeneca, Bristol Myers Squibb. Advisory board (compensation to institution): Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie. Consultancy (compensation to institution): InnoCare, AbbVie. Honorarium (to institution): Kite, JW Therapeutics. Yifan Pang: None. Ajay K. Gopal: Consultancy: Genentech, Acrotech, Beigene, Incyte, Karyopharm, Lilly, SciTech, Epizyme, Merck, Sana, Compliment, Caribou, Cellectar, ADCT, Morphosys/Incyte, Fresenius‐Kabi, Gilead, Merck, Servier, I‐Mab Bio, Janssen, SeaGen, Umoja. Honoraria: Genentech, Beigene, Incyte, Lilly, SciTech, Compliment, ADCT, Morphosys/Incyte, Merck, SeaGen. Research Funding: Beigene, Teva, Takeda, Pfizer, IgM Bio, AstraZeneca, Merck, Genmab, Gilead, BMS, Umoja, Servier, Janssen. Emily Tamar Tatoian: None. Trenton Grossfeld: None. Ryan C. Lynch: Research Funding: Cyteir, Incyte, TG Therapeutics, Pfizer, Allogene, Genentech, Foresight Diagnostics, Janssen. Consultancy: Merck, Abbvie, ADC Therapeutics, Genentech, Rapt, Foresight Diagnostics, Janssen. Edus H. Warren: None. Grzegorz S. Nowakowski is currently an employee of Daiichi Sankyo. Consultancy: Selvita, RochePharma AG, Karyopharm, Bristol Myers Squibb/Celgene, Kite/Gilead, Genmab, Kymera, TG Therapeutics, Incyte/MorphoSys, AbbVie, Debiopharm Group, Celgene, Genentech. Research Funding: MorphoSys, Celgene. Steven I. Park: Consultancy: Epizyme, Morphosys, ADC Therapeutics, Rafael Pharmaceuticals, G1 Therapeutics, Teva. Research Funding: Bristol‐Myers Squibb, Pfizer.
Conflicts of Interest
The authors declare all conflicts of interest in the Disclosures section at the end of this article. The following authors declare no conflicts of interest: Sharmila Giri, Andry Ness, Yifin Pang, Emily Tatar Tatoian, Trenton Grossfeld, and Edus H. Warren.
Supporting information
Figure S1: Swimmer plot.
Figure S2: Consolidation and maintenance: summary.
Table S1: Grade 1–2 AE occurring in > 2 patients, by frequency.
Table S2: Detail of four relapses.
Acknowledgments
This work was supported by Mayo Clinic/ACCRU (Academic & Community Cancer Research United) for regulatory, biostatistical, and data management conduct. The authors also express gratitude to research study participants and their families. This study was made possible by research funding from AstraZeneca.
Data Availability Statement
The corresponding author will make original data and the study protocol available to other investigators upon emailed request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1: Swimmer plot.
Figure S2: Consolidation and maintenance: summary.
Table S1: Grade 1–2 AE occurring in > 2 patients, by frequency.
Table S2: Detail of four relapses.
Data Availability Statement
The corresponding author will make original data and the study protocol available to other investigators upon emailed request.