PURPOSE: In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS: Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS: After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years (P < .001) and 7.1 years (P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION: The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.

Amsterdam University Medical Center Vrije Universiteit Amsterdam Cancer Center Amsterdam Amsterdam the Netherlands

Center Hospitalier Regional and University Nancy Vandoeuvre les Nancy Nancy France

Centre Henri Becquerel Rouen France

Charles University General Hospital Prague Czech Republic

Erasmus MC Cancer Institute Rotterdam the Netherlands

Hôpital Necker Institut Imagine Assistance Publique Hôpitaux de Paris University Paris Descartes Paris France

Hôpital Saint Louis Paris France

Hospices Civils de Lyon University of Lyon Pierre Benite France

Institut Gustave Roussy Villejuif France

Maria Sklodowska Curie Institute Warsaw Poland

Rigshospitalet Copenhagen Denmark

University Hospital Ludwig Maximilians University Munich Munich Germany

University Hospital Schleswig Holstein Campus Kiel Christian Albrechts University Kiel Kiel Germany

University Medical Center Groningen University of Groningen Groningen the Netherlands

University of Kiel Kiel Germany

University of Tübingen Tübingen Germany

University of Ulm Ulm Germany

VK and K Studien GbR Landshut Germany

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Comprehensive genetic analysis by targeted sequencing identifies risk factors and predicts patient outcome in Mantle Cell Lymphoma: results from the EU-MCL network trials

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ClinicalTrials.gov
NCT00209209