R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy followed by maintenance therapy with rituximab was more effective than R-FC (rituximab, fludarabine, and cyclophosphamide) followed by maintenance therapy with interferon alfa in older patients with mantle cell lymphoma, according to a recently published prospective, randomized, double-blind clinical trial (Kluin-Nelemans HC, et al. N Engl J Med. 2012;367:520-531).
“The excellent results with rituximab administered as maintenance therapy are important. Maintenance therapy with rituximab showed not only a progression-free survival benefit but also a significant survival advantage among patients who were successfully pretreated with R-CHOP,” wrote the authors.
The long-term prognosis is poor for older patients with mantle cell lymphoma. Treatment with chemotherapy achieves low rates of complete remission (CR), the authors wrote. Most older patients with mantle cell lymphoma will relapse, and better therapy is needed for this group of patients. When the trial was first initiated, the authors hoped that the fludarabine-containing regimen would perform better than it did in this trial. However, results showed that R-FC was not more effective than R-CHOP, and the fludarabine-containing regimen was more toxic.
The study enrolled 560 patients aged 60 years or older with stage II to IV mantle cell lymphoma who were randomized to receive either 6 cycles of R-FC every 28 days or to 8 cycles of R-CHOP every 21 days. Responders (n = 316) were randomized to maintenance therapy with rituximab or interferon alfa, and treatment was continued until disease progression.
Median age was 70 years, about 70% were male, and about 80% were stage IV at baseline. An intent-to-treat analysis for response was based on 532 patients. Rates of CR were similar for the regimens: 40% for R-FC and 34% for R-CHOP. However, more patients progressed on R-FC (14% vs 5% with R-CHOP). Four-year survival rates were significantly lower on R-FC: 47% versus 62%, respectively (P = .10). Also, more patients treated with R-FC died during first remission (10% vs 4%, respectively). Hematologic adverse events were reported more frequently in the R-FC group than in the R-CHOP group, but the rates of infection were similar (17% for R-FC and 14% for R-CHOP).
In the analysis of responders, maintenance therapy with rituximab reduced the risk of progression or death by 45%: progression or death occurred in 58% of those on maintenance with interferon alfa versus 29% of those on maintenance rituximab (P = .01). Among responders to R-CHOP, maintenance therapy with rituximab significantly improved overall survival at 4 years from 63% with interferon alfa maintenance to 87% (P = .005).
Toxic effects during the maintenance phase were more pronounced in the interferon alfa group, with more patients having leukocytopenia, thrombocytopenia, and fatigue, whereas rituximab was associated with more infections. These observed differences led to differences in adherence, with an overall median treatment duration of 25 months with rituximab versus 7 months with interferon alfa.