Health-Related Quality of Life in Heavily Pre-Treated and Renally Impaired Patients with Relapsed/Refractory Multiple Myeloma Receiving Isatuximab Plus Pomalidomide and Dexamethasone: Icaria-MM Study

Introduction: The phase 3 ICARIA trial demonstrated that isatuximab plus pomalidomide–dexamethasone (Isa-Pd) significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM) with a consistent benefit observed across several clinical subgroups, compared with pomalidomide–dexamethasone (Pd) alone. We aimed to assess health-related quality of life (HRQL) in patients receiving Isa-Pd or Pd, stratified by number of prior lines of therapy (PLT) (>3 vs 2–3) and by baseline (BL) creatinine clearance (<60mL/min/1.73m² vs ≥60mL/min/1.73m²).

Methods: A post-hoc analysis was conducted using data from a randomized, open-label phase 3 clinical trial (ICARIA). During the study, patients completed electronic versions of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the EORTC Myeloma-specific module (MY20) on Day 1 of each 28-day treatment cycle until progression or unacceptable toxicity. Key domains for post hoc analysis were based on a HRQL conceptual model of RRMM; key symptoms included MY20 disease symptoms (MYDS), C30 pain (PA) and C30 fatigue (FA), and key impact domains included C30 physical (PF), C30 role function (RF) and C30 global health status/quality of life (GHS/QoL). Increasing scores on the C30 GHS/QoL, PF, and RF scales indicate improvement of HRQL/function, while increasing scores on the C30 PA, FA and MY20 MYDS scales/items indicate worsening of symptoms. Mixed model for repeated measures analyses were used to assess least squares mean (LSM) change from BL for each cycle (up to cycle 17). A clinically meaningful change was defined as ≥10 points. Sensitivity analyses were conducted, excluding cycles with <20% of the BL sample size.

Results: In heavily pre-treated (HPT) (>3 PLT) patients (Isa-Pd n=47; Pd n=46), scores for GHS/QoL, PA and MYDS trended towards improvement with Isa-Pd vs Pd. A clinically meaningful improvement in PA was observed at cycles 7–10, 12–13 and 15–16 for HPT patients receiving Isa-Pd (but only at cycle 15 for those receiving Pd) (Figure, A). PF and RF were better maintained among patients receiving IsaPd vs Pd. No clinically meaningful worsening of FA was observed for HPT patients receiving Isa-Pd compared with Pd (PF shown in Figure, B). Results were similar between the two treatment arms in moderately pre-treated (2–3 PLT) patients (Isa-Pd n=92; Pd n=88). In patients with BL renal impairment (RI) (creatinine clearance <60mL/min/1.73m²: Isa-Pd n=51; Pd n=42), scores for GHS/QoL, PA and MYDS trended towards improvement with Isa-Pd; clinically meaningful improvements in PA were observed for RI patients receiving Isa-Pd at cycles 10, 13 and 15–16 (but only at cycles 16–17 for those on Pd) (Figure, C). PF and RF were better maintained for those receiving Isa-Pd vs Pd (PF shown in Figure, D). Similarly, FA was better maintained with Isa-Pd vs Pd, with a clinically meaningful worsening observed for those on Pd at cycles 5, 8 and 9. Results were comparable between the treatment arms in patients with no RI (Isa-Pd n=86; Pd n=81). Sensitivity analysis excluding cycles with <20% of BL sample size supported the primary analysis.

Conclusions: Data from the ICARIA study suggest that in two difficult-to-treat subgroups of RRMM patients (HPT and RI patients), HRQL was better maintained with Isa-Pd compared with Pd, based on key disease-relevant domains. These observations align with those reported for the intention-to-treat population in the ICARIA trial. Isatuximab provides an important new treatment option in RRMM, including difficult-to-treat subgroups of RRMM patients.