Treatment Outcomes and Roles of Transplantation and Maintenance Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma: Results From Large Real-World Cohorts

Abstract

PURPOSE Commonly used first-line (1L) treatments for mantle cell lymphoma include high-dose cytarabine-based induction followed by autologous stem-cell transplant (ASCT) for younger patients and several chemoimmunotherapy regimens for older patients. Continuous debates exist on the role of ASCT in younger patients and maintenance rituximab (MR) after bendamustine plus rituximab (BR). METHODS Retrospective data from 4,216 patients with mantle cell lymphoma in the Flatiron Health electronic record-derived deidentified database diagnosed between 2011 and 2021, mostly in US community oncology settings, were evaluated for treatment patterns and outcomes. The efficacy findings with ASCT and MR were validated in an independent cohort of 1,168 patients from 12 academic centers. RESULTS Among 3,614 patients with documented 1L treatment, BR was the most used. Among 1,265 patients age < 65 years, 30.5% received cytarabine-based induction and 23.5% received ASCT. There was no significant association between ASCT and real-world time to next treatment (hazard ratio [HR] 0.84; 95% CI, 0.68 to 1.03; P = .10) or overall survival (HR 0.86; 95% CI, 0.63 to 1.18; P = .4) among ASCT-eligible patients. Among MR-eligible patients, MR after BR versus BR alone was associated with a longer real-world time to next treatment (HR 1.96; 95% CI, 1.61 to 2.38; P < .001) and overall survival (HR 1.51; 95% CI, 1.19 to 1.92; P < .001). The efficacy findings were consistent in the validation cohort. CONCLUSION In this large cohort of patients treated primarily in the US community setting, only one in four young patients received cytarabine or ASCT consolidation, suggesting the need to develop treatments that can be delivered effectively in routine clinical practice. Together with the validation cohort, data support future clinical trials exploring regimens without ASCT consolidation in young patients, whereas MR should be considered for patients after 1L BR and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network

“…12 Interestingly, the Flatiron health electronic study retrospective analysis suggested that BR 1 R-maintenance without ASCT may provide similar outcome. 13 In future trials, ASCT may be challenged if cytarabine induction or BR complemented by targeted approaches such as BTK-inhibitors 14 achieves similar long-term results to prevent long-term toxicities. Accordingly, the TRIANGLE (ClinicalTrials.gov identifier: NCT02858258) and E4151 protocols (ClinicalTrials.gov identifier: NCT03267433) are investigating the role of ASCT.…”

Frontline Therapy in Mantle Cell Lymphoma: When Clinical Trial and Real-World Data Collide

“…In one recent analysis, 49% of patients older than 65 years received BR during 2010-2015. 35 However, there remains wide variability in practice among both community oncologists and lymphoma specialists.…”

“…The relevant literature regarding frontline therapy is then reviewed, with particular focus on selection of induction regimen and the potential roles for autologous transplantation and/or rituximab maintenance. This literature primarily consists of prospective phase 2 and phase 3 clinical trials; however, added to this literature now is a growing body of large retrospective real-world cohorts, such as the new analysis by Martin et al, 35 the manuscript that accompanies this Oncology Grand Rounds article. In some cases, the real-world evidence is at odds with data from prospective clinical trials, such as regarding the role of rituximab maintenance after bendamustine plus rituximab induction.…”

Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: a population-based analysis

“…We used similar criteria to define lines of therapy as those applied in the Flatiron Health dataset. 10 For example, any nonrituximab chemoimmunotherapy agent given within a 30-day window or rituximab within 90-day window was considered as the same line.…”

“…10,13,14 However, due to the inconsistency of findings and some limitations of these studies, there remains uncertainty in the clinical benefit. Two prior observational studies 10,13 showed similar benefits in the multivariable analysis. In contrast, the MAINTAIN trial showed no significant difference in PFS or OS between the RM and non-RM groups, despite the longer median PFS observed with RM (not reached vs. 55 months for non-RM).…”