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Postinduction Maintenance Therapy in Mantle Cell Lymphoma
Achievement of complete remission and undetectable minimal residual disease (MRD) status following induction immunochemotherapy is associated with improved outcomes for patients with mantle cell lymphoma (MCL). Investigators now report long-term follow-up of the European MCL Elderly Trial in which 560 patients ≥60 years who were not eligible for autologous stem cell transplant consolidation were randomized to either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for 8 cycles or R-FC (rituximab, fludarabine, cyclophosphamide) for 6 cycles; patients with complete or partial remission were then randomized to either maintenance rituximab or interferon-alpha (NEJM JW Oncol Hematol Aug 21 2012 and N Engl J Med 2012; 367:520).
Serial MRD determinations were made using real-time quantitative PCR (median sensitivity, 1×10−5) on peripheral blood and bone marrow samples during induction and maintenance therapy. The aims of this long-term follow-up were to determine if end-of-induction MRD status influenced the benefit of rituximab maintenance and whether de-escalation of maintenance therapy should be encouraged in MRD-negative patients.
Greater rates of MRD negativity were achieved with R-FC but with poorer overall survival (OS) versus R-CHOP, in part due to toxicity. Maintenance rituximab significantly improved outcomes compared with interferon. Informative end-of-induction MRD samples were available for 171 of 217 (79%) patients treated in France or Germany who had not progressed during induction therapy. In the R-CHOP arm, both progression-free survival and OS were significantly improved (hazard ratios, 0.23 and 0.19, respectively) in those who were MRD negative at end of induction and received maintenance rituximab. MRD-positive patients had less benefit from maintenance rituximab and an earlier time to progression.
This analysis confirms the significant benefit of maintenance rituximab following R-CHOP induction in patients who are MRD negative at the end of induction, thus refuting an approach that would de-escalate use of maintenance therapy in this setting. Alternative consolidation or maintenance therapies need to be explored for patients who are MRD positive after induction, given their short time to progression despite maintenance rituximab.
Hoster E et al.
Title: Predictive value of minimal residual disease for efficacy of rituximab maintenance in mantle cell lymphoma: Results from the European Mantle Cell Lymphoma Elderly Trial.
Source: J Clin Oncol 2023 Nov 22; [e-pub]. (Abstract/FREE Full Text)