Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial.

Abstract

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.

• Authors: Hanneke C Kluin-Nelemans, Eva Hoster, Olivier Hermine, Jan Walewski, Christian H Geisler, Marek Trneny, Stephan Stilgenbauer, Florian Kaiser, Jeanette K Doorduijn, Gilles Salles, Michal Szymczyk, Hervé Tilly, Lothar Kanz, Christian Schmidt, Pierre Feugier, Catherine Thieblemont, Josée M Zijlstra, Vincent Ribrag, Wolfram Klapper, Christiane Pott, Michael Unterhalt, Martin H Dreyling
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 3 Pg. 248-256 (01 20 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 31804876 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Vidarabine
• fludarabine
• Prednisone

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cyclophosphamide (administration & dosage)
• Doxorubicin (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Induction Chemotherapy (methods)
• Lymphoma, Mantle-Cell (drug therapy)
• Maintenance Chemotherapy (methods)
• Male
• Middle Aged
• Prednisone (administration & dosage)
• Progression-Free Survival
• Rituximab (administration & dosage)
• Time
• Vidarabine (administration & dosage, analogs & derivatives)
• Vincristine (administration & dosage)