Isatuximab Combo Shows Preliminary Activity in Pretreated Multiple Myeloma

"In this preliminary analysis, IsaPomDex demonstrated promising clinical activity, with rapid responses in [patients] with [multiple myeloma] experiencing their first relapse following treatment with a [lenalidomide]-containing regimen," according to the study authors.

Combining isatuximab-irfc (Sarclisa) with pomalidomide (Pomalyst) and dexamethasone (IsaPomDex) produced quick responses among patients with multiple myeloma and relapsed disease following 1 prior line of lenalidomide (Revlimid)-based therapy, according to preliminary findings from the phase 2 EAE115 study (NCT05298683) in Greece.1

Investigators presented these data in a poster session at the 2025 European Hematology Association Congress.

Treatment yielded an objective response rate (ORR) of 73.3% (n = 33/45), with partial responses (PRs) observed in 42.20%, very good PRs (VGPRs) in 28.90%, and complete responses (CRs) in 2.20%. Data showed a median time to first response (TTR) of 1.0 month (range, 0.9-13.8) and a median time to best response of 1.2 months (range, 0.9-13.8). Additionally, the median time to VGPR was 2.5 months (range, 1.0-6.5).

Among all evaluable patients, the median progression-free survival (PFS) was 16.8 months (95% CI, 7.9-not reached [NR]). The median time to progression (TTP) was 19.3 months (95% CI, 9.9-NR).

“In this preliminary analysis, IsaPomDex demonstrated promising clinical activity, with rapid responses in [patients] with [multiple myeloma] experiencing their first relapse following treatment with a [lenalidomide]-containing regimen,” lead study author Evangelos Terpos, MD, PhD, a professor of Hematology and director of the Stem Cell Transplantation Unit in the Department of Clinical Therapeutics of the National & Kapodistrian University of Athens School of Medicine in Athens, Greece, wrote with coauthors.1 “The safety of IsaPomDex was consistent with the known safety profile of this combination.”

As of December 16, 2024, 49 patients in the ongoing, investigator-initiated phase 2 trial were assigned to receive isatuximab at 10 mg/kg intravenously every week in cycle 1 and every 2 weeks in cycles 2 to 6, pomalidomide at 4 mg orally per day on days 1 to 21, and dexamethasone at 40 mg orally or intravenously every week or 20 mg if 75 years or older.

If patients achieved a VGPR or better during the initial period of treatment, they were randomly assigned to receive isatuximab every 4 weeks or every 2 weeks in combination with pomalidomide/dexamethasone. If patients did not have a VGPR or better during the initial period, they continued treatment with isatuximab once every 2 weeks plus pomalidomide/dexamethasone.

The trial’s primary end point is the 6-month ORR rate. Secondary end points include PFS, overall survival, minimal residual disease, TTR, duration of response, and safety.2

Patients 18 years and older with a documented diagnosis of multiple myeloma and current evidence of measurable disease and documented evidence of progressive disease per International Myeloma Working Group criteria after the last line of treatment were eligible for enrollment on the trial. An ECOG performance status of 0 to 2 was another requirement for study entry. Those with prior anti-CD38 monoclonal antibody therapy, prior exposure to pomalidomide, or stem cell transplantation within 12 weeks of beginning study treatment were ineligible for enrollment.

The median patient age was 72.0 years (range, 55.0-87.0), and most were male (61.2%). Additionally, most patients had an ECOG performance status of 0 (59.2%), International Staging System (ISS) stage I disease (63.3%), Revised ISS stage I disease (51.0%), and lytic bone lesions (51.0%). Most patients achieved a VGPR (38.8%) or PR (26.5%) as a best response to prior therapy.

The median number of completed treatment cycles was 7.0 (range, 1.0-27.0), and 69.4% received at least 6 cycles of therapy. The median treatment duration was 6.9 months (range, 0.3-25.4), and the median follow-up was 9.0 months (range, 0.5-25.4).

At least 1 treatment-emergent adverse effect (TEAE) occurred in 87.80% of patients, and 34.70% had at least 1 serious TEAE. Grade 3 or higher TEAEs affected 67.40% of patients, and at least 1 serious TEAE of grade 3 or higher occurred in 26.50%. The most common grade 3 or higher TEAEs included febrile neutropenia (6.1%) and pneumonia (6.1%).

References

1. Terpos E, Gavriatopoulou M, Spyridonidis A, et al. Isatuximab in combination with pomalidomide and dexamethasone in patients with multiple myeloma who relapsed after one line of lenalidomide-containing therapy: a phase 2 study by the Greek Myeloma Study Group. Presented at the 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract PF752.
2. A phase 2 study of isatuximab in combination with pomalidomide and dexamethasone in MM patients who received one prior line of therapy containing lenalidomide and a proteasome inhibitor. ClinicalTrials.gov. Updated March 28, 2022. Accessed June 20, 2025. https://tinyurl.com/yc23f4tk