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

Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K. Moyo, Nishitha Reddy, Julia Sheets, David M. Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C. Churnetski, Andrew Hsu, Luke Zurbriggen, Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F. Caimi, Pallawi TorkaCeleste Bello, Sabarish Ayyappan, Reem Karmali, Seo Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A. David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P. Kenkre, Adam J. Olszewski, Jonathon B. Cohen, Neil Palmisiano, Elvira Umyarova, Ryan A. Wilcox, Farrukh T. Awan, Juan Pablo Alderuccio, Stefan K. Barta, Natalie S. Grover, Nilanjan Ghosh, Nancy L. Bartlett, Alex F. Herrera, Geoffrey Shouse

Research output: Contribution to journalLetterpeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Article number96
JournalJournal of Hematology and Oncology
Issue number1
StatePublished - Dec 2022

Bibliographical note

Funding Information:
NE: Speakers Bureau for Incyte, Honoraria/consulting/ad boards for TG Therapeutics, Pharmacyclics, BeiGene, Seattle Genetics, and Novartis; Research funding BeiGene. TKM ad board for Seattle Genetics. NR: Consultancy KITE, AbbVie, BMS, Celgene; Research funding Genentech, BMS. PRG: Consultancy to Kite Pharma, Rafael Pharma, Pharmacyclics LLC, and BMS. PC: Research funding ADC Therapeutics, Genentech; Ad board: ADC Therapeutics, Genentech, Bayer, Verastem, KITE; Speakers Bureau Celgene. PT: Consulting fees from ADC Therapeutics, TG Therapeutics, Kura Oncology, and Genentech. SA: Consulting/Ad board for TG Therapeutics, Seattle Genetics, BeiGene, Intellisphere, Fate Therapeutics, AstraZeneca. RK: Advisory Board: Celgene Corporation, Gilead Sciences, Juno Therapeutics, Kite Pharma, Janssen, Karyopharm, Pharmacyclics, MorphoSys, Epizyme, Genentech/Roche, EUSA; Grants/Research Support: Celgene Corporation/Juno Therapeutics/BMS, Takeda, BeiGene, Gilead Sciences/Kite. Speakers Bureau: AstraZeneca, BeiGene, Gilead Sciences, MorphoSys. SK Consultation with Karyopharm and Incyte. YS: Research funding from BMS, Celgene, TG Therapeutics, and BeiGene and has consulted for TG Therapeutics and Epizyme. BC: Research funding: Acerta, Celgene, Genentech, Merch, Millennium, MorphoSys, Roche, Triphase; Ad board: Verastem, Seattle Genetics, AstraZeneca. MJ: Research funding Takeda, Fate, Nektar. AJO: Research funding Genentech, Spectrum Pharmaceuticals, TG Therapeutics, Adaptive Biotech. JCB: Consulting/Advisory board—Janssen, BeiGene, Astra Zeneca, Loxo/Lilly, Aptitude Health, Kite/Gilead, HutchMed; Research Funding: Astra Zeneca, BMS/Celgene, Genentech, Loxo/Lilly, Takeda, Novartis, HutchMed, BioInvent. NP: Research funding from Genentech and AbbVie. FTA: Consultancy to Genentech, AstraZeneca, AbbVie, Janssen, Pharmacyclics, Gilead Sciences, Kite Pharma, Celgene, Karyopharm, MEI Pharma, Verastem, Incyte, BeiGene, Johnson and Johnson, Dava Oncology, BMS, Merck, Cardinal Health, ADCT therapeutics, Epizyme. JPA: Consulting fees and research funding from ADC Therapeutics. SKB: Consultancy Monsanto; Honoraria: Atara, Seattle Genetics, Janssen, Pfizer. NSG: Research funding Genentech; honoraria/consulting/ad boards Kite, ADC, Novartis. NG: Consulting/advisory role for Seattle Genetics, TG Therapeutics, AstraZeneca, Pharmacyclics, BMS, Gilead, BeiGene, Incyte, Karyopharm, Roche/Genentech, Novartis, Loxo/Lilly, Genmab, Adaptive Biotech. NLB: Research funding: ADC Therapeutics, Autolus, BMS, Celgene, Forty Seven, Genentech, Immune Design, Janssen, Merck, Millennium, Pharmacyclics, Affirmed Therapeutics, Dynavax, Gilead, MedImmune, Novartis; Consulting/Ad board: Kite Pharma, Pfizer, ADC Therapeutics, Roche/Genentech, Seattle Genetics, BTG, Acerta. GS: Honoraria from Kite Pharmaceuticals and BeiGene. AFH: Consultancy: BMS, Merck, Gilead, Adaptive Biotech, Seattle Genetics, Karyopharm; Research funding: Merck, Genentech, Gilead, Seattle Genetics, Immune Design, AstraZeneca, Pharmacyclics, ADCT Therapeutics. QZ, SMC, LS, JS, DMW, MK, XJB, CT, MCC, AH, LZ, CT, KL, KM, CB, SHK, AK, KAD, IBG, VPK, EU, and RAW have no relevant COI.

Publisher Copyright:
© 2022, The Author(s).


  • Ibrutinib
  • MZL
  • Marginal zone lymphoma
  • Refractory
  • Relapsed

PubMed: MeSH publication types

  • Letter
  • Multicenter Study
  • Comment


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