Isatuximab in relapsed multiple myeloma patients with ultra-high-risk cytogenetics: ICARIA-MM and IKEMA subgroup analysis

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Patients (pts) with ultra-high-risk (UHR) multiple myeloma (MM) have even poorer prognosis than pts with no or 1 chromosomal abnormality (CA). Isatuximab (Isa) is an approved anti-CD38 monoclonal antibody that was evaluated in relapsed/refractory MM in ICARIA-MM and IKEMA. Aims: These analyses of ICARIA-MM and IKEMA data investigated Isa-Pd and Isa-Kd in pts with UHR and extended high-risk (EHR) MM. Methods: The analysis excluded pts with at least one missing CA information. Standard risk (SR) was the absence of the following CA – del(17p), t(4;14), t(14;16) and 1q21+; EHR the presence of only one of these CA, and UHR the presence of ≥2 CA. Results: In ICARIA-MM, there were 101 Isa-Pd (SR cytogenetics: 29; EHR CA: 61; UHR CA: 11) and 93 Pd (SR: 35; EHR CA: 38; UHR CA: 20) pts. In IKEMA, 154 Isa-Kd (SR: 65; EHR CA: 64; UHR CA: 25) and 103 Kd (SR: 43; EHR CA: 41; UHR CA: 19) pts were included. In both trials, all UHR pts had 1q21+, and t(4;14) was the second most frequent CA, followed by del(17p) and t(14;16). In ICARIA-MM, Isa-Pd led to a progression-free survival (PFS) benefit regardless of risk category (SR HR 0.478 [95% CI 0.263−0.866]; EHR HR 0.645 [95% CI 0.414−1.006]; UHR HR 0.437 [95% CI 0.188−1.018]). Hazard ratios for overall survival (OS) were 1.032 (95% CI 0.542−1.972), 0.842 (95% CI 0.533−1.330) and 0.796 (95% CI 0.357−1.776) for SR, EHR, and UHR pts, respectively. PFS benefits with Isa-Kd were also shown in IKEMA (SR HR 0.496 [95% CI 0.294−0.839]; EHR HR 0.531 [95% CI 0.310−0.908]; UHR HR 0.689 [95% CI 0.343−1.385]). OS data is immature. A summary of response rates for both trials is in the Table. Minimal residual disease negativity (MRD−) rate was 44.6% and 18.6% with Isa-Kd and Kd respectively in SR pts, 32.8% and 14.6% with EHR, and 28.0% and 21.1% with UHR. MRD− and complete response or higher rates were 33.8% and 11.6% with Isa-Kd and Kd in SR pts, 28.1% and 12.2% in EHR and 20.0% and 21.1% in UHR pts respectively. Summary/Conclusion: The benefit of Isa in all subgroups was consistent with the primary results of each study. A benefit in EHR pts with Isa-containing regimens vs control arms was observed, including pts with UHR, who would benefit from further improvement in outcomes.Keywords: Chromosomal abnormality, CD38, Monoclonal antibody, Multiple myeloma