Ide-Cel With R Maintenance Versus R Maintenance Alone for MM

Researchers presented the design and targeted endpoints of the phase III KarMMa-9 trial at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

Lenalidomide (R) maintenance is the standard of care in patients with newly diagnosed multiple myeloma (MM) who have undergone autologous hematopoietic stem cell transplantation (HSCT). However, in patients who have a suboptimal response to autologous HSCT, the risk of disease progression increases. The multicenter, randomized, controlled, phase III KarMMa-9 trial aims to evaluate the safety and efficacy of idecabtagene vicleucel (ide-cel) with R maintenance compared to R maintenance alone in adults with newly diagnosed MM.

The authors noted that ide-cel “showed deep, durable responses in patients with [newly diagnosed] MM who had inadequate response to front-line [autologous HSCT] in KarMMa-2 cohort 2c.”

The authors wrote that 618 patients will be randomized 1:1 to receive either ide-cel with R maintenance or R maintenance alone. All patients will receive R maintenance until they develop progressive disease or unacceptable toxicity levels.

Those on the ide-cel plus R regimen will “receive one cycle (28 days) of R (10 mg daily) within seven days post-randomization followed by leukapheresis (14–42 days after last dose of R) and lymphodepleting chemotherapy before ide-cel infusion (target dose: 300–460×10⁶ chimeric antigen receptor T cells),” the authors explained. “R maintenance will resume at one month post–ide-cel, contingent on blood cell count recovery. Patients will receive R at 5 mg once daily for the first cycle post-infusion; if tolerated, subsequent dosing will follow prescribing information.”

Progression-free survival is the primary endpoint for the phase III KarMMa-9 trial. The authors wrote that the key secondary endpoint is overall survival, and additional secondary endpoints include:

• Sustained complete remission (CR) with no detectable measurable residual disease (MRD) for 12 months
• MRD-negative CR rate
• Event-free survival
• Duration of response
• CR rate
• Time to progression
• Progression-free survival
• Safety
• Pharmacokinetics
• Health-related quality of life

The trial is supported by Celgene, a Bristol Myers Squibb company, and 2seventybio.

Reference

Raje N, Cohen A, Harrison S, et al. Efficacy and safety of idecabtagene vicleucel (ide-cel) with lenalidomide (R) maintenance versus R maintenance alone in adult patients with newly diagnosed multiple myeloma (NDMM) who have suboptimal response to autologous stem cell transplantation (ASCT): phase III KarMMa-9 trial. Abstract #MM-493. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.