Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma: a multicenter cohort study

• Type of Material: Article
• Authors: Narendranath Epperla, Ohio State University; Qiuhong Zhao, Ohio State University; Sayan Mullick Chowdhury, Ohio State University; Lauren Shea, Washington University in St. Louis; Tamara K Moyo, Atrium Health; Nishitha Reddy, Vanderbilt University; Julia Sheets, University of North Carolina; David M Weiner, University of Pennsylvania; Praveen Ramakrishnan Geethakumari, University of Texas Southwestern Medical Center; Malathii Kandarpa, University of Michigan; Ximena Jordan Bruno, University of Vermont; Colin Thomas, Thomas Jefferson University; Michael C Churnetski, Emory University; Andrew Hsu, Brown University; Luke Zurbriggen, University of Wisconsin, Madison; Cherie Tan, Cancer Institute of New Jersey; Kathryn Lindsey, Medical University of South Carolina; Joseph Maakaron, University of Minnesota, Minneapolis; 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, Ohio State University; Beth Christian, Ohio State University; Kevin A David, Cancer Institute of New Jersey; Irl B Greenwell, Medical University of South Carolina; Murali Janakiram, University of Minnesota, Minneapolis; Vaishalee P Kenkre, University of Wisconsin, Madison; Adam J Olszewski, Brown University; Jonathon Cohen, Emory University; Neil Palmisiano, Thomas Jefferson University; Elvira Umyarova, University of Vermont; Ryan A Wilcox, University of Michigan, Ann Arbor; Farrukh T Awan, University of Texas Southwestern Medical Center; Juan Pablo Alderuccio, University of Miami; Stefan K Barta, University of Pennsylvania; Natalie S Grover, University of North Carolina; Nilanjan Ghosh, Atrium Health; Nancy L Bartlett, Washington University in St. Louis; Alex F Herrera, City of Hope, Duarte; Geoffrey Shouse, City of Hope, Duarte
• Language: English
• Date: 2022-07-16
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13045-022-01316-1
• Title of Journal or Parent Work: JOURNAL OF HEMATOLOGY & ONCOLOGY
• Volume: 15
• Issue: 1
• Start Page: 96
• End Page: 96
• Grant/Funding Information: None.
• Keywords: MZL; Science & Technology; Ibrutinib; Relapsed; Oncology; Refractory; Marginal zone lymphoma; Hematology; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

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.