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

Meletios A Dimopoulos,Paul G Richardson,Xavier Leleu,Enrique M Ocio,Helgi Van De Velde,Dorothée Sémiond,Kwee Yong,Philippe Moreau,Anna Marina Liberati,Sylvie Assadourian,Frank Campana,H Miles Prince,Laure Malinge,Simon J Harrison

doi:10.1038/s41375-020-0868-z

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.

Highlights

Renal impairment (RI) affects up to 50% of patients with multiple myeloma (MM) [1]
Patients were included if they had a baseline estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2, determined using the Modification of Diet in Renal Disease (MDRD) equation [22]
307 patients were randomized to Isa-pomalidomide and dexamethasone (Pd) (n = 154) or Pd (n = 153)

Summary

Introduction

Renal impairment (RI) affects up to 50% of patients with multiple myeloma (MM) [1]. USA 5 Oncology-Hematology, Santa Maria Hospital, University of Perugia, Terni, Italy the accumulation and precipitation of immunoglobulin free light chains in the distal tubules, resulting in tubule obstruction and cast nephropathy [1]. RI is an independent predictor of adverse survival outcomes for myeloma patients [2, 3] and the median survival of patients with RI is approximately half that of patients without RI [2]. Antimyeloma treatments that can improve renal function are urgently required.

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Results

Conclusion