Real-world efficacy and safety of ixazomib maintenance therapy in Chinese patients with newly diagnosed multiple myeloma: A multicenter retrospective study

Abstract Background: Maintenance therapy plays a critical role to prolong remission and improve outcomes in multiple myeloma (MM). Ixazomib offers potential advantages in terms of convenience and tolerability, however, real-world evidence specifically in Chinese patients is limited. This multicenter retrospective study evaluated the efficacy and safety of ixazomib-based maintenance therapy in Chinese patients with newly diagnosed multiple myeloma (NDMM). Methods: We conducted a multicenter retrospective analysis across four centers in Southwest China (Jan 2020–Jul 2025). The study was approved by the institutional review boards of all participating centers. NDMM patients were stratified based on transplant status (autologous stem cell transplantation (ASCT) vs non-ASCT). Patients achieving at least a partial response (PR) after ≥2 courses of therapy (non-ASCT cohort) or achieving at least PR after ASCT (ASCT cohort) were switched to all-oral ixazomib-based maintenance regimens: ixazomib monotherapy (3 or 4 mg orally on days 1, 8, 15 of 28-day cycles) or ixazomib (same dose) plus lenalidomide (10-25 mg orally on days 1-14 or 1-21). Treatment continued until disease progression or unacceptable toxicity. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, the remission rates were compared using McNemar's test. Adverse events (AEs) were summarized using descriptive statistics. Results: A total of 222 patients were enrolled with median age 60 years (range 42-84), 29.3% ≥70 years, 49.5% patients was male. Cytogenetic risk stratification (by mSMART criteria) was available for 207 patients (93.2%), 55.1% were high-risk, 41.4% patients had R-ISS stage III. The ASCT cohort comprised 38.3% (85/222) patients, and the non-ASCT cohort 61.7% (137/222). After a median follow-up of 23 months (range 7-51), the median duration of therapy (DOT) was 7 months (95% CI: 6-9). In the ASCT cohort, median PFS was 36 months (95% CI: 28.01-43.98), median OS was not reached. After switching to ixazomib-based maintenance, ≥ VGPR rates increased from 81.2% (69/85) to 90.6% (77/85) (p< 0.05), and ≥CR rates increased from 52.9% (45/85) to 67.1% (57/85) (p = 0.017). The non-ASCT cohort (median age 68 years) had a median PFS of 28 months (95% CI: 17.65–38.34), median OS was not reached. ≥ VGPR rates improved from 65.7% (90/137) to 86.9% (119/137) (p < 0.05), and ≥ CR rates increased from 38.0% (52/137) to 56.2% (77/137) (p < 0.05). The most common all-grade AEs were hematologic toxicities: neutropenia (13.7%), thrombocytopenia (13.2%), anemia (7.5%); gastrointestinal symptoms: diarrhea (11.8%), nausea (8.9%); and peripheral neuropathy (4.2%). Grade ≥ 3 AEs included diarrhea (8.0%), hematologic toxicities (6.1%), nausea (4.3%), and peripheral neuropathy (0.5%). Treatment discontinuation due to toxicity occurred in 7.1% of patients, primarily due to gastrointestinal AEs. Conclusion: This multicenter real-world study supports the clinical efficacy and a manageable safety profile of ixazomib-based maintenance therapy. The efficacy observed in the sizable non-transplant cohort and ASCT cohort is particularly encouraging, which was consistent with outcomes observed in the pivotal TOURMALINE-MM3 and MM4 trials.