Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.

Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib +/- low-dose dexamethasone in patients who received >= 2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib +/- weekly dexamethasone 40mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; >= minimal response); secondary objectives included safety. Patients (n=92) received a median of 4 prior regimens. Ibrutinib+dexamethasone produced the highest CBR (28%) in Cohort 4 (840mg+dexamethasone; n=43), with median duration of 9.2months (range, 3.0-14.7). Progression-free survival was 4.6months (range, 0.4-17.3). Grade 3-4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3-4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib+dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment.