Ixazomib, pomalidomide and dexamethasone in triple-class exposed multiple myeloma patients - a phase II study.

Abstract

Multi-class upfront regimens for multiple myeloma (MM) have improved outcomes, yet many patients become either triple-class exposed (TCE) or refractory (TCR) early in their disease course. This is a phase II, investigator initiated, open-label, single-arm, prospective, multicenter study evaluating all-oral Ixazomib-pomalidomide- dexamethasone (IPd) regimen for TCE RRMM patients. Sixty-one patients were enrolled between March 1st 2021 and March 17th 2024. The median age was 74 (range: 53-89) years; 25 (41%) were ≥75 years old. Fiftyseven percent had high-risk cytogenetics (t(4;14), t(14;16), +1q21, del17p(. Twenty-six (43%) patients were frail. Refractoriness rates to bortezomib, lenalidomide and daratumumab were 51%, 85% and 96% respectively. Tripleclass refractory (TCR) rate was 39%. Ninety-seven percent of the patients had ≥1 treatment emergent adverse event (TEAE) and 67% had a TEAE grade ≥3. The rate of Gr ≥3 AE was not increased in frail vs. non-frail patients (p=0.43). Overall response rate (ORR) was 58% (22% very good partial response or better). TCR patients had an ORR of 46% vs. 68% for non-TCR patients (p=0.12). The median progression-free survival was 8.1 (95% CI 3.9-12.3) months and the median overall survival was 30.4 (95% CI 21.5-39.4) months. To conclude, the all-oral IPd regimen for TCE RRMM patients showed high response rates and a manageable safety profile, in a cohort enriched with TCR, elderly and frail patients. (NCT04790474).