Hanneke C Kluin-Nelemans1, Eva Hoster2, Olivier Hermine3, Jan Walewski4, Christian H Geisler5, Marek Trneny6, Stephan Stilgenbauer7, Florian Kaiser8, Jeanette K Doorduijn9, Gilles Salles10, Michal Szymczyk4, Hervé Tilly11, Lothar Kanz12, Christian Schmidt2, Pierre Feugier13, Catherine Thieblemont14, Josée M Zijlstra15, Vincent Ribrag16, Wolfram Klapper17, Christiane Pott18, Michael Unterhalt2, Martin H Dreyling2. 1. University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. 2. University Hospital Ludwig-Maximilians-University Munich, Munich, Germany. 3. Hôpital Necker, Institut Imagine, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Paris, France. 4. Maria Sklodowska-Curie Institute, Warsaw, Poland. 5. Rigshospitalet, Copenhagen, Denmark. 6. Charles University General Hospital, Prague, Czech Republic. 7. University of Ulm, Ulm, Germany. 8. VK&K Studien GbR, Landshut, Germany. 9. Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 10. Hospices Civils de Lyon, University of Lyon, Pierre-Benite, France. 11. Centre Henri Becquerel, Rouen, France. 12. University of Tübingen, Tübingen, Germany. 13. Center Hospitalier Regional and University Nancy Vandoeuvre les Nancy, Nancy, France. 14. Hôpital Saint Louis, Paris, France. 15. Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands. 16. Institut Gustave Roussy, Villejuif, France. 17. University of Kiel, Kiel, Germany. 18. University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
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.
RCT Entities:
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: Michael J Buege; Anita Kumar; Brianne N Dixon; Laura A Tang; Terry Pak; Jennifer Orozco; Tim J Peterson; Kathryn T Maples Journal: Ann Pharmacother Date: 2020-02-20 Impact factor: 3.154
Authors: Diego Villa; Laurie H Sehn; Kerry J Savage; Cynthia L Toze; Kevin Song; Wendie D den Brok; Ciara L Freeman; David W Scott; Alina S Gerrie Journal: Blood Adv Date: 2020-08-11
Authors: Reem Karmali; Jeffrey M Switchenko; Subir Goyal; Krithika Shanmugasundaram; Michael C Churnetski; Bhaskar Kolla; Veronika Bachanova; James N Gerson; Stefan K Barta; Max J Gordon; Alexey V Danilov; Natalie S Grover; Narendranath Epperla; Stephanie Mathews; Madelyn Burkart; Yazeed Sawalha; Brian T Hill; Nilanjan Ghosh; Steven I Park; David A Bond; Kami J Maddocks; Talha Badar; Timothy S Fenske; Mehdi Hamadani; Jin Guo; Mary Malecek; Brad S Kahl; Peter Martin; Kristie A Blum; Christopher R Flowers; Jonathon B Cohen Journal: Am J Hematol Date: 2021-08-10 Impact factor: 10.047