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Isatuximab Added to Pomalidomide and Dexamethasone Extends OS in Relapsed and Refractory MM
The addition of isatuximab to pomalidomide and dexamethasone extended overall survival (OS) compared to pomalidomide and dexamethasone alone among patients with lenalidomide-refractory and proteasome inhibitor-refractory or relapsed multiple myeloma (MM; Lancet Oncol. 2022;S1470-2045[22]00019-5. doi:10.1016/S1470-2045[22]00019-5).
“The primary analysis of the ICARIA-MM study showed significant improvement in progression-free survival with addition of isatuximab to pomalidomide–dexamethasone in relapsed and refractory [MM],” wrote Prof Paul G. Richardson, Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, and colleagues.
This analysis reports updated OS at 24 months after the primary analysis.
The phase 3 ICARIA-MM study enrolled patients aged ≥18 years with relapsed and refractory MM who received ≥2 lines of prior therapy, including lenalidomide and a proteasome inhibitor. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. The study was conducted in 102 hospitals in 24 countries. Patients were excluded if they had anti-CD38 refractory disease or previously received pomalidomide.
Patients were randomly assigned in a 1:1 ratio to isatuximab plus pomalidomide and dexamethasone (isatuximab group) or pomalidomide and dexamethasone (control group). Patients were stratified by number of prior lines of therapy (2 to 3 vs >3) and age (<75 vs ≥75 years).
Patients in the isatuximab group received isatuximab 10 mg/kg on days 1 to 21 of each cycle, and then on day 1 and 15 of each cycle thereafter. Both groups received oral pomalidomide 4 mg on day 1 to 21 of each cycle, and weekly oral or intravenous dexamethasone 40 mg (20 mg if aged ≥75 years) on days 1, 8, 15, and 22 of each cycle.
Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. This analysis reports on updated OS, a key secondary end point, in the intention-to-treat population at 24 months after the primary analysis. Safety was assessed in all patients who received ≥1 dose or part dose of study treatment.
A total of 307 patients were included in the study and randomized to the isatuximab group (n = 154) or control group (n = 153) between January 10, 2017, and February 2, 2018. Median follow-up at data cutoff (October 1, 2020) was 35.3 months. Median OS was 24.6 months in the isatuximab group and 17.7 months in the control group (hazard ratio [HR] 0.76; one-sided long-rank P = .028).
Grade ≥3 neutropenia occurred in 76 (50%) of 152 patients in the isatuximab group vs 52 (35%) of 149 patients in the control group. Grade ≥3 pneumonia occurred in 35 (23%) vs 31 (21) patients, respectively. Grade ≥3 thrombocytopenia occurred in 20 (13%) vs 18 (12%) patients, respectively.
Serious treatment-emergent adverse events (AEs) occurred in 111 (73%) patients in the isatuximab group and 90 (60%) patients in the control group. Treatment-emergent AEs resulting in death occurred in 2 (1%) patients and 2 (1%) patients in the control group.
“Addition of isatuximab plus pomalidomide–dexamethasone resulted in a 6.9-month difference in median overall survival compared with pomalidomide–dexamethasone and is a new standard of care for lenalidomide-refractory and proteasome inhibitor-refractory or relapsed multiple myeloma,” concluded Dr Richardson and colleagues.
