Updated results of the ICARIA-MM study demonstrated that addition of isatuximab to pomalidomide/low-dose dexamethasone led to significant improvements in efficacy outcomes compared with pomalidomide/low-dose dexamethasone alone in patients with RRMM.
The randomized phase 3 ICARIA-MM study (NCT02990338) evaluated the safety and efficacy of the addition of isatuximab to pomalidomide and low-dose dexamethasone (Isa-Pd) versus Pd alone in patients with relapsed/refractory multiple myeloma (RRMM). Second interim analysis results of the ICARIA-MM study were presented at the 2021 EHA Annual Meeting and summarized here.
The study enrolled patients with RRMM who had received ≥2 previous therapies, including lenalidomide and a proteasome inhibitor. Eligible patients were randomized to receive Isa-Pd or Pd; isatuximab was administered intravenously at 10 mg/kg weekly for 4 weeks and every other week thereafter. This preplanned analysis assessed time to next treatment (TTNT), overall survival, time from randomization to disease progression on first subsequent therapy or death (PFS2), and safety. The data cutoff date was October 1, 2020.
A total of 307 patients were enrolled in the study; of these, 154 received Isa-Pd and 153 received Pd. Patients had received a median of 3 previous lines of therapy. At data cutoff, 27 (18%) patients in the Isa-Pd group and 12 (8%) patients in the Pd group were still receiving treatment; 60% versus 72% proceeded to subsequent therapy, respectively.
At a median follow-up of 35.3 months, median TTNT was significantly longer in the Isa-Pd group than in the Pd group (15.5 months vs 8.9 months; hazard ratio [HR], 0.56; P <.0001). Among patients who received subsequent therapy, a lower proportion of patients in the Isa-Pd group received the anti-CD38 monoclonal antibody daratumumab versus the Pd group (24% vs 58%, respectively); overall response rate in subsequent treatment with daratumumab monotherapy was lower in Isa-Pd than in Pd (14% vs 38%, respectively) but similar (31% vs 32%, respectively) with daratumumab combination therapy (plus immunomodulator, plus alkylator, plus a proteasome inhibitor). In the intent-to-treat population, median PFS2 was significantly longer in the Isa-Pd group than in the Pd group (17.5 months vs 12.9 months, respectively; HR, 0.76; 95% confidence interval, 0.58-0.99; P = .0202). Median overall survival was also significantly improved in the Isa-Pd versus Pd group (24.6 months vs 17.7 months, respectively; HR, 0.76; one-sided P = .0280). Median treatment duration was 47.6 weeks in the Isa-Pd group compared with 24.0 weeks in the Pd group.
Serious treatment-emergent adverse events (TEAEs) occurred in 73% of patients in the Isa-Pd group compared with 60% in the Pd group. In the Isa-Pd group, the most common nonhematologic any grade TEAEs included infusion reaction (38%), upper respiratory tract infection (34%), and diarrhea (30%). Grade 3/4 hematologic TEAEs occurred more frequently in the Isa-Pd group than in the Pd group, including neutropenia (85% vs 71%, respectively) and thrombocytopenia (34% vs 25%, respectively).
Updated results of the ICARIA-MM study demonstrated significant improvement in TTNT and PFS2 with the addition of isatuximab to Pd compared with Pd alone in patients with RRMM, which translated into a strong trend in overall survival benefit favoring the Isa-Pd group.
Source: Perrot A, Richardson P, San-Miguel J, et al. Updates from ICARIA-MM, a phase 3 study of isatuximab (ISA) plus pomalidomide and low-dose dexamethasone (Pd) versus Pd in relapsed and refractory multiple myeloma (RRMM). Presented at: 26th Annual Congress of European Hematology Association; June 9-17, 2021; Virtual. Abstract S186.
