Both this retrospective analysis of the ICARIA-MM study data and the phase 1b TCD14079 study data aimed to evaluate the efficacy of isatuximab (Isa) with pomalidomide-dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM) with the gain(1q21) chromosomal abnormality.
In these studies, CD138+ plasma cells were collected from patients who had received ≥2 prior lines of therapy to evaluate cytogenetic risk. In ICARIA-MM versus TCD14079, gain(1q21) abnormalities were detected differently. In ICARIA-MM, cytogenetic risk was assessed using fluorescence in situ hybridization testing of CD138+ plasma cells from baseline bone marrow aspirate. In TCD14079, if ≥3 copies of 1q were present in >9% of analyzed cells, then a gain(1q21) abnormality was recorded.
In the ICARIA-MM study, 154 patients with RRMM were randomly assigned to receive Isa-Pd, whereas 153 patients received Pd. Of these 307 total patients, 41.7% (128 patients) had gain(1q21), and there were no additional high-risk cytogenetic abnormalities in 27.7% (85 patients) of the patient population. Isa-Pd had a positive effect in patients with isolated gain(1q21). For patients treated with Isa-Pd, median progression-free survival (PFS) was 11.2 months versus 4.6 months for patients treated with Pd alone (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.28-0.88). For patients without a gain(1q21) abnormality and standard risk, median PFS rates were 15.2 months and 9.8 months for those treated with Isa-Pd and Pd alone (HR, 0.64; 95% CI, 0.29-1.38), respectively. Overall response rate (ORR) was higher with treatment with Isa-Pd than with Pd alone regardless of whether the patient had gain(1q21). For patients with isolated gain(1q21), ORRs were 53.6% and 27.6% for those treated with Isa-Pd and Pd alone, respectively. For patients without gain(1q21) and standard risk, ORRs were 79.3% and 45.7% for treatment with Isa-Pd and Pd alone, respectively. The Isa-Pd group had a higher rate of very good partial response or better (≥VGPR) than did the Pd group. For patients with isolated gain(1q21), Isa-Pd was associated with ≥VGPR in 25.0% of patients taking Isa-Pd versus 3.4% of those taking Pd. For patients without gain(1q21), Isa-Pd was associated with ≥VGPR in 34.5% of patients versus 11.5% of those taking Pd.
In the TCD14079 study, 40 patients with RRMM who were not previously treated with daratumumab were treated with Isa plus standard doses of Pd. Of these patients, 10 (25%) patients had gain(1q21) and 6 (15%) patients had isolated gain(1q21). PFS was not reached for isolated gain(1q21). The ORR was 50% in 3 patients responding (95% CI, 0.1-0.9). A ≥VGPR was achieved in 33.3% of patients with isolated gain(1q21).
Based on these analyses, the researchers concluded that the addition of Isa to Pd resulted in a consistent positive treatment effect in the poor-risk subgroup of patients with isolated gain(1q21).
Reference
Abstract and Poster EP1017. EHA 2020. June 12, 2020. Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with 1q21 gain: insights from phase 1 and phase 3 studies.