Subcutaneous Isatuximab Demonstrates Comparable Efficacy in Myeloma

In a pivotal phase 3 study known as IRAKLIA, researchers have demonstrated that subcutaneously administered isatuximab (Sarclisa) is non-inferior to its intravenous counterpart for patients with relapsed or refractory multiple myeloma. The findings were presented at the 2025 European Hematology Association Congress, highlighting the innovative on-body delivery injector (OBI) designed to enhance patient convenience and clinical efficiency.

The IRAKLIA study (NCT05405166) involved 531 patients who had previously undergone at least one line of therapy. Participants were randomly assigned to receive either the intravenous form of isatuximab or the subcutaneous formulation via the OBI, along with pomalidomide (Pomalyst) and dexamethasone. The study aimed to assess the overall response rate (ORR) and the pharmacokinetics of both delivery methods.

According to Dr. Xavier Leleu, MD, PhD, from Service d’Hématologie et Thérapie Cellulaire, CHU Poitiers in France and the study's lead author, the results showed that the ORR for the Isa SC OBI plus pomalidomide and dexamethasone was 71.1%, slightly surpassing the 70.5% achieved with the intravenous formulation. This non-inferiority was statistically significant, with a relative risk of 1.008 and a p-value of 0.0006, indicating that the new delivery method maintains comparable efficacy.

The study also assessed key secondary endpoints, including the very good partial response (VGPR) rate, which reached 46.4% in the subcutaneous group compared to 45.9% in the intravenous group, further supporting the efficacy of the OBI method. Importantly, the safety profiles were similar between both treatment arms, with no new safety signals identified for the subcutaneous formulation.

The innovative OBI system allows for a hands-free administration of isatuximab, which is designed to minimize patient discomfort and logistical challenges associated with intravenous infusions. Patients reported a higher satisfaction rate with the subcutaneous method, with 70% expressing satisfaction compared to 53.4% in the intravenous group.

This study builds on previous FDA approvals of intravenous isatuximab, which have established the drug as a standard of care in multiple myeloma treatment. Since its initial approval in March 2020, isatuximab has been cleared for various combinations in relapsed and refractory myeloma cases, enhancing treatment options for patients with this challenging disease.

As the landscape of multiple myeloma therapy continues to evolve, the introduction of subcutaneous isatuximab via the OBI represents a significant advance in treatment administration, potentially leading to improved patient experiences and adherence to therapy. Future studies will likely focus on long-term outcomes and further validation of the OBI's impact on quality of life for myeloma patients.