Narendranath Epperla, The Ohio State University
Qiuhong Zhao, The Ohio State University
Sayan Mullick Chowdhury, The Ohio State University
Lauren Shea, Washington University in St. Louis
Tamara K Moyo, Atrium Health
Nishitha Reddy, Vanderbilt University Medical Center
Julia Sheets, University of North Carolina
David M Weiner, Perelman School of Medicine at the University of Pennsylvania
Praveen Ramakrishnan Geethakumari, University of Texas Southwestern Medical Center
Malathi Kandarpa, University of Michigan
Ximena Jordan Bruno, University of Vermont
Colin Thomas, Thomas Jefferson UniversityFollow
Michael C Churnetski, Emory University Medical Center
Andrew Hsu, Brown University
Luke Zurbriggen, University of Wisconsin
Cherie Tan, Cancer Institute of New Jersey
Kathryn Lindsey, Medical University of South Carolina
Joseph Maakaron, University of Minnesota
Paolo F Caimi, University Hospitals Seidman Cancer Center
Pallawi Torka, Roswell Park Cancer Institute
Celeste Bello, H. Lee Moffitt Cancer Center and Research Institute
Sabarish Ayyappan, University of Iowa
Reem Karmali, Northwestern University
Seo-Hyun Kim, Rush University
Anna Kress, Yale University
Shalin Kothari, Yale University
Yazeed Sawalha, The Ohio State University
Beth Christian, The Ohio State University
Kevin A David, Cancer Institute of New Jersey
Irl Brian Greenwell, Medical University of South Carolina
Murali Janakiram, University of Minnesota
Vaishalee P Kenkre, University of Wisconsin
Adam J Olszewski, Brown University
Jonathon B Cohen, Emory University Medical Center
Neil D. Palmisiano, Thomas Jefferson UniversityFollow
Elvira Umyarova, University of Vermont
Ryan A Wilcox, University of Michigan
Farrukh T Awan, University of Texas Southwestern Medical Center
Juan Pablo Alderuccio, University of Miami
Stefan K Barta, Perelman School of Medicine at the University of Pennsylvania
Natalie S Grover, University of North Carolina
Nilanjan Ghosh, Levine Cancer Center
Nancy L Bartlett, Washington University in St. Louis
Alex F Herrera, City of Hope
Geoffrey Shouse, City of Hope

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Publication Date



This article is the author’s final published version in Journal of Hematology and Oncology, Volume 15, Issue 1, December 2022, Article number 96.

The published version is available at Copyright © Epperla et al.


Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23-7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03-8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17-37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15-12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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