Impact of best response to ibrutinib plus Bendamustine and rituximab on PFS in MCL: a secondary analysis of SHINE.

Abstract

Ibrutinib is a first-in-class oral inhibitor of Bruton's tyrosine kinase, which was investigated for the first-line treatment of mantle cell lymphoma (MCL) in the randomized, double-blind, phase 3 SHINE study. In SHINE, ibrutinib plus bendamustine and rituximab (BR) demonstrated superior progression-free survival (PFS) versus placebo plus BR in patients aged ≥ 65 years with previously untreated stage II-IV MCL. In this secondary efficacy analysis of SHINE, we assessed the correlation between best response and PFS (n = 523; 70% male; median age 71.0 years). After a median follow-up of 94.5 months, patients achieving complete response (CR) had longer median PFS in the ibrutinib (97.8 months) and placebo (87.9 months) arms than those with partial response (PR; 27.6 and 16.7 months, respectively) or progressive/stable disease (2.9 and 3.4 months, respectively). In the multivariate logistic regression analysis, patients receiving ibrutinib plus BR were more likely to achieve CR than those receiving placebo plus BR (odds ratio 1.48; 95% confidence interval 1.00-2.22). In conclusion, prolonged long-term PFS was more likely in patients with MCL who achieved CR following treatment with either ibrutinib plus BR or placebo plus BR, while CR was more likely in patients who had received ibrutinib plus BR. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) identifier 2012-004056-11 (registered 15 January 2013) WHO Universal Trial Number U1111-1137-0389.