A dexamethasone-free daratumumab-ixazomib regimen in frail elderly patients with relapsed or refractory multiple myeloma: Results of the IFM 2018-02 phase II study.

Abstract

The combination of CD38 immunotherapy and proteasome inhibition has shown synergistic activity. Elderly relapsed or refractory multiple myeloma (RRMM) experience worse outcomes due to variabilities in fitness and higher rates of adverse events (AEs) and treatment discontinuations. The Intergroupe Francophone du Myélome (IFM) 2018-02 trial (NCT03757221) evaluated a dexamethasone-free regimen of daratumumab and ixazomib (I-Dara) in elderly frail RRMM. This prospective, phase 2 trial was conducted at 14 IFM centres. Patients aged ≥65 years with International Myeloma Working Group frailty score ≥2 and an Eastern Cooperative Oncology Group 0-2 in first or second relapse received daratumumab 16 mg/kg; ixazomib 4 mg weekly d1, d8, d15 in a 28-day cycle; and methylprednisolone. The primary end-point was ≥ very good partial response (VGPR) rate. Of 55 patients included, the median age was 82 years, with 90% aged over 75. VGPR or better was 32%. With a median follow-up of 35.3 months, the median progression-free survival time was 19.5 months. The median OS was not reached: 75% at 33.6 months. Grade ≥3 AEs occurred in 36 (67%) patients: cytopenias in 18 and infection in 8 (6 pneumonia). The IFM 2018-02 shows that I-Dara demonstrated an acceptable safety profile for this elderly frail RRMM patients' population. The response rates and survival outcomes were acceptable given the studied population.