Quadruplet Therapy Shows Promising Results as Salvage Therapy for Relapsed/Refractory Multiple Myeloma

Interim analysis from a phase 2 study suggest that the addition of ixazomib to daratumumab plus pomalidomide and dexamethasone (DIPd) resulted in promising response rates among patients with multiple myeloma (MM), according to a poster presented at the 19th Annual Meeting and Exposition of the International Myeloma Society.

The use of quadruplet therapy has increased for the treatment of newly diagnosed MM. The aim of this study was to determine if quadruplet therapy could be beneficial in the relapsed/refractory setting.

The multicenter, open-label, phase 2 study treated 32 patients with relapsed/refractory MM with DIPd. Participants included 6 patients who were treated as part of a safety run-in cohort, 8 patients treated in stage 1, and 23 patients treated in stage 2. Starting doses were reduced in stage 1 and 2 after the safety run-in. Daratumumab was reduced from 16 mg/m² IV to 1800 mg SQ, ixazomib was decreased from 4 to 3 mg weekly, and pomalidomide was reduced from 4 mg to 3 mg daily for 21 days in a 28-day cycle.

The primary endpoints were overall response rate (ORR) and safety. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and rate of minimal residual disease (MRD) negativity.

At baseline, the median age was 61.5 and approximately half of patients were female. The median number of prior lines of therapy was 1 (range, 1-3), and nearly half of the patients evaluated by fluorescence in situ hybridization had a high-risk profile.

The ORR was 83%, with 57% of patients achieving a very good partial response (VGPR) or better, including 13% with a complete response (CR), and 20% with a suspected CR. The median time to response was 1 month. The median OS was 38.9 months and the median PFS was 9.5 months.

The most common grade 3-4 treatment-emergent adverse events (AEs) were neutropenia and infection. There were 2 grade 5 AEs, including 1 each of febrile neutropenia and 1 lung infection.

The authors concluded that “the quadruplet regimen DIPd has shown manageable safety, efficacy, and ORR for patients with relapsed/refractory MM.” They added that “starting dose reductions have allowed for ongoing safe treatment.”

Disclosures: This study was supported by Takeda Research & Development, Celgene Corporation, and Janssen Research & Development, LLC. Please see the original reference for a full list of disclosures.

Reference

Kumar AD, Rosenberg A, Padilla M, et al. Phase II study of the combination of daratumumab, ixazomib, pomalidomide, and dexamethasone as salvage therapy in relapsed/refractory multiple myeloma. Presented at IMS 2022; August 25-27, 2022. Abstract P-252.

This article originally appeared on Hematology Advisor