Real-world efficacy and tolerability of ixazomib-based combination therapies in advanced multiple myeloma and other plasma cell neoplasms.

Abstract

Background: Ixazomib is an oral proteasome inhibitor for relapsed/refractory multiple myeloma (RRMM). Our study aimed to analyze the efficacy and tolerability of ixazomib-based combination therapies.

Methods: We performed a single-center retrospective analysis of 126 patients with RRMM and other plasma cell neoplasms.

Results: The median age was 65 years, with a median of two prior therapy lines, and 16.7% were triple-class refractory. The overall response rate (ORR) was 52.5%; triple-class refractory patients had a significantly lower ORR than non-refractory controls (10.5% vs 60.2%, p < 0.001). After a median follow-up of 27.0 months, the median progression-free survival (PFS) was 7.9 months (95% CI: 6.9-11.0), and the median overall survival (OS) was 84.1 months (95% CI: 68.1-not reached). In multivariate analysis, a glomerular filtration rate of ⩽70 ml/min/1.73 m² was linked to worse PFS (hazard ratio (HR): 2.11, p = 0.008) and OS (HR: 7.27, p = 0.003). Furthermore, triple-class refractory patients showed a trend toward inferior PFS (HR: 3.76, p = 0.05) and significantly worse OS (HR: 20.46, p = 0.002) compared to non-refractory patients. Grade ⩾3 hematologic adverse events occurred in 15.1% patients, while the most common non-hematologic adverse events were fatigue (5.6%) and peripheral neuropathy (26.2%), with the majority classified as grade 1-2.

Conclusion: Altogether, ixazomib regimens are potent in RRMM but are less effective in heavily pretreated patients and those with renal impairment, suggesting earlier use may yield greater benefits.