Isa-VRd Meets Primary End Point in Transplant-Ineligible Newly Diagnosed Multiple Myeloma

The primary end point of very good partial response (VGPR) or better rate at 8 months was met with subcutaneous isatuximab-irfc (Sarclisa) as a flat dose plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Isa-VRd) in patients with transplant-ineligible newly diagnosed multiple myeloma, according to results from the phase 2 ISASOCUT trial (NCT04653246) presented at the 22nd International Myeloma Society Annual Meeting.

The median follow-up for response and minimal residual disease (MRD)-negativity rates was 11.73 months. The VGPR or better rate was 87.8% (95% CI, 78%-94%). MRD-negative rate at 10^-5 was 35.1%, and at 10^-6 was 27.0%. The stringent complete response (CR)/CR rate with MRD-negativity at 10^-5 was 61%. The median time to a VGPR or better was 3.71 months (95% CI, 2.333-3.778).

“These findings support the use of [subcutaneous isatuximab] plus VRd as a new standard of care for [newly diagnosed multiple myeloma in patients who are transplant ineligible], providing a longer induction schedule but lower dose intensity compared with the phase 3 IMROZ study [NCT03319667],” Arthur Bobin, MD, from the University of Poitiers, and lead author of the study, said during the presentation.

A total of 74 patients were enrolled in the open-label trial. From cycles 1 to 12, patients were given subcutaneous isatuximab at 1400 mg weekly during cycle 1, and on days 1 and 15 from cycles 2 to 12; lenalidomide was given at 25 mg by mouth on days 1 and 21; dexamethasone was given by mouth at 20 mg weekly; and bortezomib was given subcutaneously at 1.3 mg/m² twice weekly during cycle 1 and weekly during cycles 2 to 12. For cycle 13 onwards, patients were given monthly subcutaneous isatuximab at 1400 mg and lenalidomide at 25 mg on days 1 and 21.

The primary end point was the VGPR or better rate at 8 months. Secondary end points included safety, response rates, duration of response, time to first and best response, survival, and MRD negativity.

At the data cutoff of January 13, 2025, 4 patients had discontinued treatment, no relapses had been observed, and 2 patients had died.

A total of 51% of patients were male, the median patient age was 73 years, and 31% were older than 75 years. Additionally, 55% of patients had an ECOG performance status of 1, 47% had an International Staging System (ISS) stage of 2, 47% had a Revised ISS of 2, and 86% had standard risk cytogenetics.

Any grade adverse effects (AEs) occurred in 100% of patients, and 89% had grade 3 or higher. Serious AEs occurred in 45%. Drug-related AEs of grade 3 or higher occurred in 64% of patients, and 49% had drug-related grade 3 or higher AEs which led to a dose modification. Two patients had grade 5 AEs.

Any grade and grade 3 or higher hematologic AEs included anemia (99% vs 10%, respectively), thrombocytopenia (85% vs 26%), neutropenia (76% vs 49%), and lymphopenia (93% vs 65%). Noted infections included pneumonia (5% vs 1%), COVID-19 (9% vs 1%), and upper respiratory infection (1% vs 0%). Peripheral sensory neuropathy occurred in 47% vs 3%, respectively. Additional AEs included constipation (43% vs 3%), insomnia (26% vs 0%), diarrhea (41% vs 0%), and asthenia (31% vs 3%).

The investigators noted no new safety signals were reported in this trial.

Infusion reaction was observed in 5% of patients across all grades of AEs. Injection-site reactions occurred in 28% of patients for all grades and 5.4% for grade 2. Of the 1853 injections, injection-site reactions occurred in 2.05% of all injections.

The median duration of isatuximab injection was 12 minutes. The relative dose intensity was 96.2% (95% CI, 92.8%-100.0%).

Reference

Bobin A, Durocher L, Ragot S, et al. Subcutaneous isatuximab flat dose by on-body injector plus bortezomib, lenalidomide, and dexamethasone in newly diagnosed transplant-ineligible multiple myeloma: phase 2 ISASOCUT (IFM 2022-05) study. Presented at the 22nd International Myeloma Society Annual Meeting; Toronto, Canada; September 17-20, 2025. Abstract OA-46.