Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation

Mehdi Hamadani, Parameswaran N. Hari, Ying Zhang, Jeanette Carreras, Görgün Akpek, Mahmoud D. Aljurf, Ernesto Ayala, Veronika Bachanova, Andy I. Chen, Yi Bin Chen, Luciano J. Costa, Timothy S. Fenske, César O. Freytes, Siddhartha Ganguly, Mark S. Hertzberg, Leona A. Holmberg, David J. Inwards, Rammurti T. Kamble, Edward J. Kanfer, Hillard M. LazarusDavid I. Marks, Taiga Nishihori, Richard Olsson, Nishitha M. Reddy, David A. Rizzieri, Bipin N. Savani, Melhem Solh, Julie M. Vose, Baldeep Wirk, David G. Maloney, Sonali M. Smith, Silvia Montoto, Wael Saber

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

The poor prognosis for patients with diffuse large Bcell lymphoma (DLBCL) who relapse within 1year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1year of initial diagnosis. The ERF cohort was compared with those relapsing >1year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P=34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P <001) within the first 9months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.

Original languageEnglish (US)
Pages (from-to)1729-1736
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number11
DOIs
StatePublished - Nov 1 2014

Bibliographical note

Funding Information:
The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute , the National Heart, Lung and Blood Institute and the National Institute of Allergy and Infectious Diseases ; a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and National Cancer Institute ; a contract HHSH250201200016C with Health Resources and Services Administration; 2 Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research ; and grants from * Actinium Pharmaceuticals ; Allos Therapeutics, Inc. ; * Amgen, Inc. ; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation ; * Blue Cross and Blue Shield Association ; * Celgene ; Chimerix, Inc. ; Fred Hutchinson Cancer Research Center ; Fresenius-Biotech North America, Inc. ; * Gamida Cell Teva Joint Venture Ltd. ; Genentech, Inc. ; * Gentium SpA ; Genzyme Corporation ; GlaxoSmithKline ; Health Research, Inc. ; ROSWELL PARK CANCER INSTITUTE ; HistoGenetics, Inc. ; Incyte Corporation ; Jeff Gordon Children's Foundation ; Kiadis Pharma ; The Leukemia & Lymphoma Society; Medac GmbH ; The Medical College of Wisconsin ; Merck & Co., Inc. ; Millennium: The Takeda Oncology Co. ; * Milliman USA, Inc. ; * Miltenyi Biotec, Inc. ; National Marrow Donor Program ; Onyx Pharmaceuticals ; Optum Healthcare Solutions, Inc. ; Osiris Therapeutics, Inc. ; Otsuka America Pharmaceutical, Inc. ; Perkin Elmer, Inc. ; * Remedy Informatics ; * Sanofi US ; Seattle Genetics ; Sigma-Tau Pharmaceuticals ; Soligenix, Inc. ; St. Baldrick's Foundation ; StemCyte , A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc. ; Swedish Orphan Biovitrum ; * Tarix Pharmaceuticals ; * Terumo BCT ; * Teva Neuroscience, Inc. ; * Texas Instruments Inc. ; University of Minnesota ; University of Utah ; and * WellPoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government.

Keywords

  • Aggressive lymphoma
  • Autologous transplantation
  • Diffuse large Bcell lymphoma
  • Early failure
  • High-dose therapy
  • Non-Hodgkin lymphoma
  • Rituximab

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