Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma.

ABSTRACT: In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4?mg), pomalidomide (Pom: 4?mg), and dexamethasone (Dex: 40?mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3?mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose-limiting. Per 3?+?3 phase I design, an additional three patients were enrolled to DL1, with no further dose-limiting toxicity (DLT). At dose level 2 (DL2, 4?mg Ixa), 1/3 patients had dose-limiting febrile neutropenia, neutropenia, and thrombocytopenia (grade 4 each). DL2 was expanded to enroll three additional patients with no further DLT, establishing the recommended phase II dose (RP2D). In phase II, 19 additional patients were treated at RP2D. With a median follow-up of 11.9 months, 48% achieved ???partial response (PR), with 5 patients (20%) achieving very good partial response (VGPR) and 76% experiencing???stable disease. The most common adverse events (?grade 2) were anemia, neutropenia, thrombocytopenia, and infections. Peripheral neuropathy was infrequent. In summary, Ixa/Pom/Dex is a well-tolerated and effective oral combination therapy for patients with relapsed/refractory MM.

SUBMITTER: Krishnan A 

PROVIDER: S-EPMC6005710 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature