Dr Baz on the Background of the KarMMa-3 Trial in Relapsed/Refractory Multiple Myeloma

Rachid Baz, MD, hematologist, medical oncologist, head, Myeloma Section, the Department of Malignant Hematology, codirector, the Pentecost Family Myeloma Research Center, Moffitt Cancer Center, discusses the use of idecabtagene vicleucel (ide-cel; Abecma) vs standard regimens in patients with triple-class–exposed, relapsed/refractory multiple myeloma, highlighting an analysis of cytopenias and infections in patients from the phase 3 KarMMa-3 trial (NCT03651128).

The KarMMa-3 trial assessed ide-cel, a CAR T-cell product, in patients with advanced multiple myeloma, for which limited treatment options exist, Baz begins. The preceding phase 2 KarMMa study (NCT03361748) indicated a high response rate and significant progression-free survival benefits for patients with relapsed/refractory multiple myeloma who received ide-cel, particularly those who had received a median of 5 or 6 prior lines of treatment, Baz explains.

Within patients enrolled in the KarMMa-3 trial, most severe cytopenias linked to ide-cel manifested early, and there was minimal occurrence of prolonged cytopenias, most of which were manageable. The prevalence of bacterial infections decreased over time, although the incidence of viral infections exhibited a stable pattern. Notably, no novel safety concerns arose with the use of ide-cel in this trial, and its safety profile remained consistent with earlier reports.

With response rates reaching 81% in patients in KarMMa who received ide-cel at the target dose of 450×106 CAR+ T cells, the question arose whether this treatment could be administered earlier in the disease course, he expands. This prompted KarMMa-3, which randomly assigned patients who had received 2 to 4 prior lines of treatment 2:1 to receive ide-cel or 1 of 5 commonly used chemotherapy regimens, Baz states. There was no crossover option for patients progressing on standard chemotherapy regimens, he elucidates.

Eligible patients needed to have triple-class-exposed disease, meaning prior exposure to lenalidomide or an immunomodulatory drug; prior exposure to carfilzomib (Kyprolis), bortezomib (Velcade), or a proteasome inhibitor; and prior exposure to CD-38 antibodies, Bazcontinues. The primary adverse effect observed with ide-cel was cytokine release syndrome, accompanied by cytopenias and infection risks. To provide a comprehensive understanding, investigators compared these safety findings with those in patients receiving other myeloma therapies after 2 to 4 prior lines of therapy, he concludes.