Combination of daratumumab, ixazomib, and lenalidomide with or without dexamethasone for initial therapy of newly diagnosed myeloma.

Authors

Shaji Kumar, Betsy Knopf, Erik Asmus, Eli Muchtar, Francis K Buadi, Wilson Gonsalves, Melanie Thompson, David Dingli, Ronald Go, Rahma Warsame, Taxiarchis Kourelis, Lisa Hwa, Amie Fonder, Miriam Hobbs, Angela Dispenzieri, Suzanne Hayman, Nelson Leung, Moritz Binder, S Vincent Rajkumar, Morie Gertz, Prashant Kapoor

Published in

Blood cancer journal. Jul 18, 2026. Epub Jul 18, 2026.

Abstract

Quadruplets incorporating anti-CD38 monoclonal antibody have led to improved outcomes, potentially allowing limited-duration therapy and reduction in steroid doses. We designed this trial to examine the efficacy of the quadruplet regimen containing daratumumab, ixazomib, lenalidomide, and dexamethasone (Dara-IRd) given for fixed duration and to evaluate early discontinuation of steroids. Patients with untreated MM were enrolled, irrespective of their transplant eligibility. The primary objective was to determine the ≥complete response (CR) rate. Treatment involved 28-day cycles of ixazomib 4 mg days 1, 8, 15; lenalidomide 25 mg days 1-21, dexamethasone 40 mg, weekly and daratumumab 16 mg/kg, weekly for two cycles, every other week during cycles 3-6 and every 4-weeks thereafter during induction (12-cycles) followed by daratumumab and ixazomib maintenance (24-cycles). Seventy-eight patients were enrolled into two sequential cohorts: cohort A (n = 38) and B (N = 40), with dexamethasone given only for two cycles in Cohort B. At the time of the data cut-off, all patients had completed the treatment. The overall response rate was 96%, including a ≥CR rate of 32%, similar in both cohorts. Responses deepened over time; 32% achieved a marrow MRD negative status and 29% MRD_neg-CR. After a median follow-up of 37.9 months, the median PFS or OS has not been reached. A grade ≥3 adverse event, at least possibly attributed to the study drugs, was seen in 55% of patients. The most common toxicities included fatigue, neutropenia, lymphopenia, peripheral neuropathy, diarrhea, and nausea. Stem cells were collected in 55 patients; the median sCD34+ cell yield (range) was 7.8 (2.8-15.9) × 10⁶/kg. Dara-IRd is an active regimen in newly diagnosed MM, with high overall response rate as well as deep responses. Nearly a third of the patients attained MRD_neg status, which improved over time. The PFS with finite-duration therapy is comparable to other studies in NDMM. Early discontinuation of dexamethasone did not impact efficacy.

PMID:
42471354
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.

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