The combination of isatuximab, bortezomib, and lenalidomide with limited dexamethasone is a feasible treatment option for transplant-ineligible older patients with multiple myeloma (MM), according to the REST study, which was led by Frida Bugge Askeland, MD, of the Oslo University Hospital in Norway, and published in the Lancet Haematology.

The researchers assessed the combination that limited dexamethasone in order to reduce the risk of infection that is associated with the long-term use of corticosteroids.

The academic, multicenter, single-arm, phase 2 study included adults with newly diagnosed MM who were ineligible for high-dose melphalan and autologous hematopoietic stem cell transplantation (HSCT).

Between June 30, 2021, and January 19, 2023, 51 patients were enrolled and received:

Isatuximab 10 mg/kg intravenously on days one, eight, 15, and 22 of cycle one and days one and 15 of cycles two to 18
Bortezomib 1.3 mg/m²subcutaneously on days one, eight, and 15 of cycles one to eight
Lenalidomide 25 mg orally on days one to 21 until disease progression
Dexamethasone 20 mg orally on days one, eight, 15, and 22 only during the first 2 cycles

The median age was 77 years, and 53% were female; 39 patients completed the intended 18 cycles of treatment.

At a median follow-up of 27 months, 19 patients (37%) experienced measurable residual disease-negative complete responses, with a median treatment duration of 22 months.

Disease progression or death occurred in 18 (35%) patients, including eight (16%) deaths. Two deaths (pneumonia and sepsis) were deemed “possibly” related to the study treatment.

During the first 18 cycles, the most common grade 3/4 adverse events were neutropenia (55%), infections (41%), and thrombocytopenia (22%). More than half of patients (53%) reported grade ≥3 serious adverse events. More than a quarter of patients (27%) discontinued treatment before cycle 19, most commonly due to disease progression (16%) and adverse events (8%).

“Isatuximab, weekly bortezomib, and lenalidomide with limited dexamethasone was active and safe as initial therapy for older patients with [MM] ineligible for autologous HSCT,” the researchers concluded.

The study was funded by Sanofi.

Reference

Askeland FB, Haukås E, Slørdahl TS, et al. Isatuximab, bortezomib, lenalidomide, and limited dexamethasone in patients with transplant-ineligible multiple myeloma (REST): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2025;12(2):e120-e127. doi:10.1016/S2352-3026(24)00347-8