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.

Real-world renal function among patients with multiple myeloma in the United States

“…In this study, MM patients with renal impairment were more likely to be older and to present with ISS stage III at diagnosis, which has been reported in a previous phase III study 11 . Patients with renal impairment exhibited decreased OS compared with non-renally impaired patients.…”

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma

“…The median PFS was 11.5 months in the Isa-Pd arm vs. 6.5 months in Pd arm (HR, 0.596, p = 0.001) [37]. Subgroup analysis of this trial showed significant improvement of PFS in patients with renal impairment (<60 mL/min/1.73 m 2 ), PFS was 9.5 months in Isa-Pd arm and 3.7 months in Pd arm (HR 0.50, p not reported) [38]. The effect was also maintained in elderly population including patients >75 years [39].…”

Isatuximab, a novel anti-CD38 monoclonal antibody in the treatment of multiple myeloma: efficacy and safety

“…Добавление изатуксимаба к схеме терапии не сопровождалось увеличением частоты отмены терапии и изменениями в качестве жизни (по опроснику QLQ-30) [16]; а в обеих прогностически неблагоприятных подгруппах пациентов с РРММ (тяжело предлеченных -более 3 линий предшествующей терапии и у пациентов с ПН) качество жизни, связанное с состоянием здоровья, лучше поддерживалось на триплете I-Pd по сравнению с дуплетом Pd [19].…”

“…Отдельного внимания заслуживает анализ данных не только эффективности, но и безопасности комбинации I-Pd у пациентов с ПН, так как нарушения функций почек часто встречаются в популяции пациентов с ММ и связаны как с самим заболеванием, так и с назначаемой терапией. Согласно данным подгруппового анализа в исследовании ICARIA-MM [16] у пациентов с ПН медиана полученных циклов терапии не отличалась от таковой у пациентов без ПН и составила соответственно 10 циклов (1-18) против 10 циклов (1-19) [16]. Частота НЯ, впервые возникших или ухудшившихся после начала исследуемой терапии ≥3-й степени тяжести, была сравнимой у пациентов с ПН и без нее (90,7% против 86%) в группе пациентов, получавших I-Pd.…”