Rituximab Maintenance Added to Ibrutinib-Containing Therapy in Younger, Untreated Patients With Mantle Cell Lymphoma: Results From the TRIANGLE Trial
Abstract
The TRIANGLE trial established an ibrutinib-containing therapy without autologous stem-cell transplantation (ASCT) as the new standard for younger, treatment-naïve patients with mantle cell lymphoma (MCL). However, the benefit of rituximab maintenance (RM) within this novel standard is unclear. We investigated whether RM improves progression-free survival (PFS) and overall survival (OS) with acceptable toxicity when added to the experimental arms of TRIANGLE. This secondary analysis of TRIANGLE included patients randomly assigned to ibrutinib-containing therapy without (I) or with (A + I) ASCT who responded to induction/ASCT. RM was given per national and center practice. PFS and OS of patients with and without RM were compared with inverse probability of treatment weighted Kaplan-Meier curves and log-rank tests. Among responders after induction/ASCT (I: 274; A + I: 237), RM was given to 61% (I) and 64% (A + I). RM prolonged PFS in ibrutinib-containing treatment arms (I: log-rank test: P = .003, 4-year PFS probability RM v no RM, 85% v 73%; A + I: P < .001, 90% v 75%). There were trends toward prolonged OS in RM groups. RM groups were at higher risk of grade 3 to 5 infectious toxicity (I: 34% v 11%; A + I: 41% v 18%). Our findings support adding RM to BTK inhibitor treatments in younger, untreated patients with MCL to achieve prolonged remission.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (40)
Marco Ladetto
1University of Eastern Piedmont, Department of Translational Medicine, Novara, Italy
Katja Gutmair
2Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), LMU University, Munich, Germany
Rita Tavarozzi
4Memorial Sloan Kettering Cancer Center, New York, NY
Alexandra Pawlikowski
Department of Medicine III, LMU University Hospital, Munich, Germany
Michael Schomaker
Department of Statistics, Ludwig-Maximilians Universität München, Munich, Germany
Jeanette Doorduijn
13Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Hematology, on behalf of the Lunenburg Lymphoma Phase I/II Consortium – HOVON/LLPC, Rotterdam, Netherlands
Eva Giné
Mats Jerkeman
Jan Walewski
16Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Martin Hutchings
15Department of Haematology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
Ulrich Mey
17Kantonsspital Graubuenden, Oncology and Hematology, for the Swiss Group for Clinical Cancer Research (SAKK), Chur, Switzerland
Jon Riise
16Oslo University Hospital, Oslo, Norway
Marek Trneny
Vibeke K.J. Vergote
Department of Hematology, University Hospitals Leuven, Leuven, Belgium
Netanel A. Horowitz
The Department of Hematology and BMT, Rambam Health Care Campus, Haifa, Israel
Maria Gomes Da Silva
22Departamento Hematologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
Sirpa Leppä
Linmiao Jiang
Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), LMU Medizin, Ludwig-Maximilians-Universität München, Munich, Germany
Stephan Stilgenbauer
Division of CLL, Department of Internal Medicine III, Ulm University, Ulm, Germany
Andrea Kerkhoff
7Medizinische Klinik A, University Hospital Münster, Münster, Germany
Ron D. Jachimowicz
Georg Hess
4Department of Hematology/Oncology, Johannes Gutenberg-Universität Mainz, Mainz, Germany
Tom van Meerten
Stefan Wirths
Peter Herhaus
4Clinic and Policlinic for Internal Medicine III, Klinikum Rechts der Isar, School of Medicine, Technical University Munich, Munich, Germany
Urban Novak
4Swiss Group for Clinical Cancer Research, Bern, Switzerland
Judith Dierlamm
9University Hospital Hamburg-Eppendorf, Hamburg, Germany
Mathias Hänel
7Department III of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany
Christine Hanoun
Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany
Kristina Sonnevi
17Karolinska University Hospital, Karolinska, Sweden
Carlo Visco
University of Verona, Verona, Italy
Claudia Castellino
3Division of Hematology, Azienda Ospedaliera S. Croce e Carle, Cuneo, Italy
Roberto Massimo Lemoli
Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
Vittorio Ruggero Zilioli
12Division of Hematology, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy
Carola Boccomini
Azienda Ospedaliero–Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
Christiane Pott
6University Hospital Schleswig-Holstein, Department of Internal Medicine II, Kiel, Germany
Wolfram Klapper
Christian Schmidt
Medical Research Council Prion Unit at University College London, University College London Institute of Prion Diseases
Martin Dreyling
LMU Hospital, Munich, Germany
Eva Hoster
24Ludwig-Maximilian-University, Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Munich, Germany