Isatuximab plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients with Gain(1q21)

This retrospective analysis of data from the ICARIA-MM study and the phase 1b TCD14079 study aimed to evaluate the efficacy of isatuximab (Isa) with pomalidomide-dexamethasone (Pd) in patients with multiple myeloma with the gain(1q21) chromosomal abnormality. In these studies, CD138+ plasma cells were collected for cytogenetics risk evaluation from patients who had received ≥2 prior lines of therapy. Gain(1q21) abnormalities were detected differently in ICARIA-MM than in TCD14079. In ICARIA-MM, cytogenetic risk was assessed using fluorescence in situ hybridization testing of CD138+ plasma cells from baseline bone marrow aspirate, whereas in TCD14079, a gain(1q21) abnormality was recorded if ≥3 copies of 1q were present in >9% of analyzed cells.

In the ICARIA-MM study, 154 patients with relapsed/refractory multiple myeloma were randomly assigned to receive Isa-Pd, while 153 patients received Pd. Of these 307 total patients, 41.7% (128 patients) had gain(1q21), and in 27.7% (85 patients) of the patient population, there were no additional high-risk cytogenetic abnormalities. In patients with isolated gain(1q21), Isa-Pd had a positive effect. Median progression-free survival was 11.2 months for patients treated with Isa-Pd and 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 progression-free survival was 15.2 months for those treated with Isa-Pd and 9.8 months for those treated with Pd alone (HR, 0.64; 95% CI, 0.29-1.38). The overall response rate was higher with Isa-Pd treatment than with Pd alone regardless of whether the patient had gain(1q21). For patients with isolated gain(1q21), the overall response rate to Isa-Pd was 53.6% versus 27.6% for Pd alone. For those without gain(1q21) and standard risk, the overall response rate to Isa-Pd was 79.3% versus 45.7% for Pd alone. The Isa-Pd group had a higher rate of very good partial response (VGPR) or better than the Pd group. For patients with isolated gain(1q21), Isa-Pd was associated with VGPR or better in 25.0% of patients taking Isa-Pd versus 3.4% of patients taking Pd. For patients without gain(1q21), Isa-Pd was associated with VGPR or better in 34.5% of patients versus 11.5% for patients taking Pd.

In TCD14079, 40 patients with relapsed/refractory multiple myeloma who were not previously treated with daratumumab were given treatment with Isa plus standard doses of Pd. Of these patients, 25% (10 patients) had gain(1q21) and 15% (6 patients) of the patient population had isolated gain(1q21). In this study, progression-free survival was not reached for isolated gain(1q21). The overall response rate was 50% (3 patients responding; 95% CI, 0.1-0.9). VGPR or better was achieved in 33.3% of patients with isolated gain(1q21).

The researchers concluded from their analyses 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).

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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.