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.

FIG 1.

Study flow. 1L, first-line; 2L, second-line; ASCT, autologous stem-cell transplant; BR, bendamustine plus rituximab; MCL, mantle cell lymphoma; MR, maintenance rituximab; Obi, obinutuzumab; OS, overall survival; PFS, progression-free survival; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; SCT, stem-cell transplant.

FIG 2.

1L mantle cell lymphoma treatment by age and year from the Flatiron cohort: patients age (A) < 65 years (n = 1,265) and (B) ≥ 65 years (n = 2,329). ^aAmong 3,614 treated patients, other therapies include 9.5% of targeted agents (eg, bortezomib, lenalidomide, BTK inhibitor, and BCL-2 inhibitor), 7.8% of immunotherapy only, 4.7% of clinical trial drugs, 2.4% of chemotherapy only, and additional 1.8% of other types of chemoimmunotherapy. ^bNumber of patients treated between 2011 and 2020 (different from n = 1,274 in Table 1, which also includes patients treated in 2021). ^cCytarabine-containing regimens include all regimens with the record of cytarabine within 1L treatment (such as hyper-CVAD, NORDIC, and alternating R-CHOP/R-DHAP). 1L, first-line; BR, bendamustine plus rituximab; hyper-CVAD, cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine; NORDIC, dose-intensified rituximab plus cyclophosphamide, vincristine, doxorubicin, prednisone alternating with rituximab plus high-dose cytarabine; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; R-DHAP, rituximab plus dexamethasone, cytarabine, and platinum.

FIG 3.

rwTTNT and OS in patients with documented first-line mantle cell lymphoma treatment from the Flatiron cohort (A) overall and by age and (B) by treatment (BR, R-CHOP, and cytarabine). BR, bendamustine plus rituximab; NE, not estimable; OS, overall survival; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; rwTTNT, real-world time to next treatment.

FIG 4.

rwTTNT and OS in the MR-eligible cohort: (A) patients treated with BR or R-CHOP alone, or BR + MR and R-CHOP + MR from the Flatiron cohort; (B) MVA of the predictors of rwTTNT and OS in the MR-eligible cohort from the Flatiron cohort; the MVA used all data, including missing values, as a category for covariates; (C) PFS and OS in the validation cohort. HR was calculated for MR yes versus no in the Flatiron cohort and MR no versus yes in the validation cohort. Median OS should be interpreted with caution as it was reached when few patients were still at risk. ^a“Bulky” as per local oncologist definition. BR, bendamustine plus rituximab; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; LDH, lactate dehydrogenase; MCL, mantle cell lymphoma; MR, maintenance rituximab; MVA, multivariate analysis; NE, not estimable; NR, not reached; OS, overall survival; PFS, progression-free survival; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; rwTTNT, real-world time to next treatment; ULN, upper limit of normal.

FIG 5.

(A) rwTTNT and OS in the ASCT-eligible cohort by ASCT status (yes v no) in the Flatiron cohort; (B) PFS and OS in the validation cohort. Median OS should be interpreted with caution as it was reached when few patients were still at risk. ASCT, autologous stem-cell transplant; HR, hazard ratio; NE, not estimable; NR, not reached; OS, overall survival; PFS, progression-free survival; rwTTNT, real-world time to next treatment.