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

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.

Advances in the treatment of relapsed/refractory marginal zone lymphoma

“…In addition, the findings in a large multicenter retrospective study by Epperla et al. were consistent with those of the PCYC1121 study ( 37 , 38 ).…”

“…Based on this study, ibrutinib was approved in 2017 for patients with R/R MZL who received at least one CD20containing monotherapy. In addition, the findings in a large multicenter retrospective study by Epperla et al were consistent with those of the PCYC1121 study (37,38).…”

Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies

“…More studies such as head-to-head comparisons are warranted to guide on the optimal treatment option. The outcomes of patients who progress following BTK inhibitors, especially those with primary resistant disease, are dismal [ 170 , 171 ]. There are several therapies in trials that will provide valuable information in the future.…”