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

## TL;DR

Ixazomib-based treatments work well for advanced multiple myeloma but are less effective in patients with severe prior treatment or kidney issues.

## Contribution

This study provides real-world evidence on the effectiveness and safety of ixazomib in relapsed/refractory multiple myeloma and related conditions.

## Key findings

- The overall response rate was 52.5%, significantly lower in triple-class refractory patients.
- Patients with a glomerular filtration rate ≤70 ml/min/1.73m² had worse progression-free and overall survival.
- Peripheral neuropathy was the most common non-hematologic adverse event, mostly mild to moderate.

## Abstract

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.

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

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.

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.