Treatment of older patients with mantle-cell lymphoma.

BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).

Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network.

BACKGROUND: Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. PATIENTS AND METHODS: We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. RESULTS: The crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status ≥2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of ≥1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood cell count at diagnosis <10.9 × 109/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem cell transplant and achievement of complete response were all associated with improved survival. CONCLUSIONS: In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.