After remission induction by initial therapy, maintenance rituximab therapy has been evaluated for patients who have received chemotherapy only or those with chemotherapy and autologous HCT.
Currently, the only prospective trial showing overall survival (OS) benefit is in the nontransplant setting following R-CHOP or R-FC (rituximab/fludarabine/cyclophosphamide) chemotherapy performed by the European Mantle Cell Lymphoma Network. This study showed a 4-year OS of 87% for those receiving rituximab maintenance compared with 63% for those receiving interferon alpha maintenance.14
In the autologous HCT setting, support for rituximab maintenance therapy comes from a number of sources. The CALGB 59909 study was a single-arm study showing the efficacy of rituximab along with induction therapy and dose-intensive therapy with autologous HCT followed by a short course of rituximab maintenance. This study showed the feasibility of additional rituximab with 2-year and 5-year PFS of 76% and 56%, respectively.11
Using a preemptive approach, the Nordic MCL-2 study showed both feasibility and a suggestion of delayed time to clinical relapse for intervention with rituximab in those patients who showed molecular relapse. In this study, molecular relapse was defined by increasing PCR-detectable markers following induction and autologous HCT using a BEAM transplant regimen.15 The prospective randomized French GOELAMS LyMa trial compared rituximab maintenance therapy for 3 years compared with no further therapy following first-line autologous HCT. This trial has recently closed and the results have not yet been presented.
While we currently await results of the LyMa trial, it is not possible to uniformly recommend rituximab maintenance to all patients following autologous HCT. Nonetheless, the Nordic MCL-2 study with intervention for molecular relapse and the demonstrated benefit in the nontransplant setting in older patients are compelling, and the generally well-tolerated administration of rituximab, all suggest consideration of rituximab maintenance in select patients until the outcome of the LyMa study is available for review.
Other agents that have demonstrated activity in MCL and have been considered as maintenance following autologous HCT include bortezomib, lenalidomide, and ibrutinib, with lenalidomide being currently studied by the Italian Lymphoma Foundation.
Other Considerations
For those patients who relapse following initial chemotherapy, autologous HCT can be considered following effective debulking chemotherapy. While historically, this group of patients was considered incurable with either chemotherapy or autologous HCT, newer evidence suggests that certain subsets of those patients can be effectively treated with autologous HCT.16 Depending on the number of adverse factors identified, the 5-year progression-free and overall survivals can range from 58% to 15% and from 76% to 32%, respectively.
For those patients who relapse following front-line autologous HCT, select patients with responsive disease, good performance status, and an available donor can be considered for reduced-intensity allogeneic transplantation.17
With the addition of new drugs and potential combinations, it is possible that dose intensification with autologous HCT will come to play a smaller role in the overall therapy of patients with MCL. However, this will require careful assessment in prospective randomized trials, along with better identification of specific patient subsets as well as a more thorough understanding of molecular prognostic and predictive factors.
For patients beyond first remission, autologous HCT can still be of value in those without prior HCT, and in select situations, reduced-intensity allogeneic transplantation also can be considered. Given all these issues, it is strongly encouraged that treating physicians work in concert with HCT programs soon after initial diagnosis so that decisions regarding initial therapy and timing of transplantation can be optimized.
Author disclosures
The author reports no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the author and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
