Phase 2 Study of Combo Therapy Shows Promise for Patients With Mantle Cell Lymphoma

David Bai, PharmD

A phase 2 trial demonstrated that the regimen of rituximab, bortezomib, bendamustine, and dexamethasone is a viable treatment option for older patients with mantle cell lymphoma (MCL). It also highlighted the usefulness of using minimal residual disease (MRD) to guide early and late clinical decisions.

MCL is a subtype of non-Hodgkin lymphoma that is typically diagnosed in the mid- to late 60s. Because of the late median age at diagnosis, most patients are not well suited to receive intensive chemotherapy or stem cell transplants and instead are given R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by maintenance therapy. Although this regimen has been shown to improve response duration and overall survival (OS), complete response (CR) rates and progression free survival (PFS) remain low.

In previous studies, a regimen consisting of bendamustine with rituximab had achieved encouraging results, with high overall response rates (ORR) for patients with relapsed or refractory MCL. Based on these results, a phase 2 trial was conducted by the authors to access the efficacy of a regimen consisting of rituximab, bortezomib, bendamustine, and dexamethasone for first-line therapy in older patients with MCL.

In this study, 74 patients with MCL received treatment, with most of them (80%) receiving all 6 planned cycles. After 4 cycles, the ORR was 86.5% and CR rate was 56.5%; after treatment, ORR was 84% and CR rate was 75.5%. Fluorodeoxyglucose-positron emission tomography to detect malignant lesions were negative in 78% (46/59) of the evaluable patients at the end of treatment. At the 2-year follow-up, PFS was 70.3% and OS was 81.1%. Four-year PFS and OS were 57.6% and 71.3%, respectively.

Of the 57 patients who had their molecular MRD analyzed, 50 patients were negative and 7 were positive at the 4-cycle mark. After 6 cycles of treatment, 41 of the 54 analyzed patients were MRD negative and 13 were MRD positive. Unlike Ki67 expression and clinical responses, MRD was a highly predictive factor for both PFS and OS (P < .0001). The 4-year OS for patients who were MRD negative at the end of treatment was considerably higher (86.6%) compared with MRD-positive patients (28.6%). Similarly, 4-year PFS for MRD-negative was 97%, compared with patients who remained MRD positive (median PFS, 11 months) and patients who converted to MRD positive by the 12-month follow-up (median PFS, 26 months).

The results from this study not only demonstrated that rituximab, bendamustine, bortezomib, and dexamethasone is a reasonable treatment regimen in older patients with MCL but also emphasized the predictive value of MRD. Because MRD was the most highly predictive factor for PFS and OS found in this study, investigators suggest using MRD to assist in clinical decisions regarding treatment in the future.

Gressin R, Daguindau N, Tempescul A, et al. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first line treatment of older patients with mantle cell lymphoma. Haematologica. 2019;104(1):138-146. doi: 10.3324/haematol.2018.191429.

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