Transition to ixazomib-based maintenance following daratumumab-based induction for continuous therapy in newly diagnosed multiple myeloma

Abstract

Abstract Background:Continuous treatment is essential for achieving sustained disease control in multiple myeloma (MM). Daratumumab(Dara)-based regimens have demonstrated significant efficacy in the induction phase. However, transitioning to a more convenient and tolerable maintenance strategy, such as ixazomib-based regimen, may offer benefits. Real-world data on transitioning from Dara-based regimens to ixazomib maintenance are limited. Objective:To evaluate the efficacy, safety, and feasibility of transitioning from Dara-based therapy to ixazomib-based maintenance in a real-world cohort of newly diagnosed multiple myeloma (NDMM) patients. Methods:This multicenter, retrospective study included NDMM patients from four Southwest China centers (Jan 2020- Jul 2025). Eligible patients received ≥ 2 cycles of Dara-based induction, achieved ≥ minor response (MR), and subsequently transitioned to ixazomib-based oral maintenance. Maintenance regimens comprised: ixazomib monotherapy (3 or 4 mg orally, days 1, 8, 15; 28-day cycles) or combination therapy: ixazomib (same dose) + lenalidomide (10-25 mg orally, days 1-14/21) or pomalidomide (2-4 mg orally, days 1-21); oral dexamethasone use was permitted. Collected data encompassed baseline characteristics, treatment details, response rates (IMWG criteria), progression-free survival (PFS), overall survival (OS), and treatment-emergent adverse events (CTCAE 5.0 criteria). Statistical analyses employed Kaplan-Meier methods for PFS/OS and descriptive statistics for safety. Results:59 patients met eligibility criteria and were analyzed. Thirty (50.85%) patients were male, median age was 65 years (range 42-84), 16 (27.12%) patients were older than 70 years. Thirty-six (61.01%) had high-risk cytogenetics (del 17p, t (4;14), t (14;16), gain or amp1q), 31 (52.5%) had R-ISS stage III, 1 (1.70%) had extramedullary disease, 40 (67.80%) were non-transplant-eligible. Median prior treatment cycles was 6 (range 2-14), 38 (64.41%) patients received to quadruplet regimens: (DVRd:54.24%; DVCd: 6.78%; DVPd: 1.69%; DKPd: 1.69%). Twenty-one (35.59%) received triplet regimens (DRd: 30.51%; DVd:5.08%). Maintenance regimens included: IR (ixazomib, lenalidomide) 28 (47.46%), ixazomib monotherapy 20 (33.90%), and IP (ixazomib, pomalidomide) 11 (18.64%) . At a median follow-up time 23 months (range 4-71), the median time on maintenance therapy was 5 months (range1-45). Median PFS was not reached, the 2-year PFS rate was 54.72%, the 2-year OS rate was 94.0%. Post Dara-based treatments, ≥ very good partial responses (VGPR) was 76.27% (45/59), ≥ complete remission (CR) rate was 44.07% (26/59). Following ixazomib-based oral maintenance, the ≥ VGPR rate improved to 88.14% (52/59), the ≥ CR rate improved to 59.32% (35/59). The most common adverse events (AEs) were hematologic (neutropenia: 8.47%, grade ≥ 3: 1.69%; thrombocytopenia: 6.78%, grade ≥ 3: 3.39%; anemia: 6.78%, grade ≥ 3: 1.69% ), gastrointestinal (diarrhea: 6.78%, grade ≥ 3: 5.08%; nausea: 6.78%, grade ≥ 3: 3.39%), and peripheral neuropathy (1.69%, grade 2). Discontinuation due to adverse events occurred in 5.08% (3/59)) patients. Conclusion:Transitioning to ixazomib-based maintenance regimen following Dara-based regimens is a feasible and effective strategy for NDMM patients in the real world. This approach demonstrates a favorable safety profile, maintains or deepens responses, and offers enhanced convenience, supporting its utility as a sustainable long-term treatment option.