Updates from the EAE115 and IONA-MM studies

Isatuximab-pomalidomide-dexamethasone for the treatment of relapsed/refractory multiple myeloma.

The combination of isatuximab, pomalidomide and dexamethasone (Isa-Pd) is currently EMA approved for the treatment of multiple myeloma (MM) patients who received at least 2 prior lines of therapy. In this video, Prof Fredrik Schjesvold, head of the Oslo myeloma center in Oslo (Norway), discusses the results of the EAE 115 study evaluating this regimen as a second line treatment for patients with relapsed/refractory MM.1 In addition, he touches upon the results of IONA-MM, a multinational study evaluating the efficacy and safety of Isa-Pd and of isatuximab-carfilzomib-dexamethasone (Isa-Kd) in a real-world setting.2

EAE115 is an ongoing phase II study performed by the Greek Myeloma group which investigates the safety and efficacy of Isa-Pd as a treatment regimen for MM patients who received only one prior line of therapy containing lenalidomide and a proteasome inhibitor. After 6 cycles of Isa-Pd, patients with a very good partial response (VGPR) or better are randomized to continue the Isa-Pd regimen in the classical bi-monthly schedule, or to switch to a once monthly treatment. At the time of the presented analysis, 39 of the planned 108 patient have been enrolled in the study. Efficacy results in this study are currently limited to response data, indicating a good objective response rate (ORR) of 73.5%, including 29.4% of patients with a VGPR or better. The safety profile of Isa-Pd was in line with what has been described in previous studies with this regimen. For the moment, data are not yet available for progression-free survival (PFS), or for the comparison between the monthly and bi-monthly treatment schedule.

IONA-MM is an ongoing, multinational observational study collecting real-world data with Isa-based therapies in patients with RRMM. At the time of the analysis, the study included 230 Isa-Pd and 156 Isa-Kd treated RRMM patients. Importantly, the proportion of patients receiving the Isa-based regimen in second line was markedly higher for Isa-Kd than for Isa-Pd at 42.2% and 20.6%, respectively.2 The real-world data obtained with Isa-Kd in this study were in line with the results of the IKEMA trial, with a median PFS that was not yet reached and an ORR of 75.7% (47.7% ≥VGPR). Interestingly, the median PFS seen with Isa-Pd was numerically longer in IONA-MM than in the pivotal ICARIA-MM study at 20.4 and 11.5 months, respectively. This difference is likely related to the fact that patients in ICARIA-MM were more heavily pretreated (median number of therapies 3 vs 2 in IONA-MM) and given the fact that ICARIA-MM included a higher proportion of lenalidomide-refractory patients (90% vs. ~60% in IONA-MM).2

For Prof Schjesvold, these data confirm Isa-Kd as a standard second line treatment for patients with RRMM. In addition to this, Isa-Pd can be a feasible 2nd line alternative for patients presenting with certain comorbidities precluding the use of carfilzomib, or for patients who prefer the more convenient pomalidomide-containing therapy. However, the fact that Isa-Pd is currently not EMA approved in 2nd line stands in the way of its use in this setting.