Long-term follow-up of the randomized, open label, phase 3 European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209) confirmed the 2012 primary readout that rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by rituximab maintenance until progression in older patients with MCL results in superior clinical outcomes and supports maintenance with rituximab extending beyond 2 years as safe and effective.
Median follow-up of this updated readout, published in the Journal of Clinical Oncology, was 7.6 years. Previously, overall survival (OS) was superior in the R-CHOP group (280 patients) compared with the rituximab, fludarabine, and cyclophosphamide (R-FC) group (280 patients), and improvements persisted, with a median OS of 6.4 years in the R-CHOP arm and 3.9 years in the R-FC arm (P =.0054).
In the original trial design, patients who responded to induction were randomly assigned to receive maintenance with either rituximab (87 patients) or interferon alfa (97) until progression.
Patients who received rituximab maintenance after responding to R-CHOP induction had a median progression-free survival (PFS) of 5.4 years and a median OS of 9.8 years. In comparison, in patients who received interferon alfa maintenance, median PFS was significantly shorter at 1.9 years (P <.001), as was median OS at 7.1 years (P =.0026).
At 2 years after initiation of R-CHOP, 58% of responders assigned to rituximab maintenance were still on therapy. At 5 years, this proportion decreased to 32%.
Following R-FC, maintenance with rituximab was correlated with a surprisingly high incidence of death in remission at 5 years of 22%. Following R-CHOP, rituximab maintenance was associated with low toxicity, with grade 3 to 4 leukopenia or infection occurring in fewer than 5% of patients. The postinduction toxicity profile of rituximab maintenance was more pronounced in the R-FC arm, with grade 3 to 4 leukopenia occurring in up to 40% of patients and frequent grade 3 to 4 infections occurring in up to 15% of patients.
“In conclusion, the excellent results of R-CHOP followed by rituximab maintenance for older patients with MCL persisted in a mature follow-up,” wrote the researchers. “Prolongation of rituximab maintenance beyond 2 or 3 years is effective and safe.”
- Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of older patients with mantle cell lymphoma (MCL): long-term follow-up of the Randomized European MCL Elderly Trial [published online December 5, 2019]. J Clin Oncol. doi:10.1200/JCO.19.01294