Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis

Abstract

The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ≥2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ≥60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates.

Fig. 1. Progression-free survival.

Patients with eGFR <60 mL/min/1.73 m² (a), <45 mL/min/1.73 m² (b), and ≥60 mL/min/1.73 m² (c) in the Isa-Pd and Pd arms. CI confidence interval, eGFR estimated glomerular filtration rate, HR hazard ratio, Isa-Pd isatuximab, pomalidomide, and dexamethasone, Pd pomalidomide and dexamethasone, PFS progression-free survival.

Fig. 2. Overall survival.

Patients with eGFR <60 mL/min/1.73 m² (a), <45 mL/min/1.73 m² (b) and ≥60 mL/min/1.73 m² (c) in the Isa-Pd and Pd arms. CI confidence interval, eGFR estimated glomerular filtration rate, HR hazard ratio, Isa-Pd isatuximab, pomalidomide, and dexamethasone, OS overall survival, Pd pomalidomide and dexamethasone, NR not reached.

Fig. 3. Response rates.

Overall response rate and depth of response according to renal function in patients treated with Isa-Pd and Pd. ^†One patient in each arm had eGFR <30 mL/min/1.73 m²; the treatment response was stable disease for the patient in the Isa-Pd arm and progressive disease for the patient in the Pd arm. CR complete response, eGFR estimated glomerular filtration rate, Isa-Pd isatuximab, pomalidomide, and dexamethasone, ORR overall response rate, Pd pomalidomide and dexamethasone, PR partial response, sCR stringent complete response, VGPR very good partial response.

Fig. 4. Renal response.

Complete and durable (≥60 days) renal responses in patients with eGFR <50 mL/min/1.73 m² at baseline in the Isa-Pd and Pd arms. eGFR estimated glomerular filtration rate, Isa-Pd isatuximab, pomalidomide, and dexamethasone, Pd pomalidomide and dexamethasone.