Subcutaneous Isatuximab On-Body Injector Shows High Reliability, Favorable Safety Across Multiple Myeloma Trials

With the treatment landscape for multiple myeloma (MM) progressively evolving, the efforts to improve patient experience and reduce treatment burden have grown increasingly crucial. Subcutaneous (SC) administration of anti-CD38 monoclonal antibodies has emerged as one strategy to streamline care, reducing infusion times and potentially increasing convenience for patients.

Emerging data presented at the 2026 American Society of Clinical Oncology Annual Meeting demonstrated that a novel SC on-body injector (OBI) for isatuximab (Sarclisa; Sanofi) achieved exceptionally high delivery success rates with low rates of infusion-related and injection-site reactions across 3 clinical trials. These findings support its potential as a future administration option for patients with relapsed/refractory MM (RRMM).

Advancing Drug Delivery in Multiple Myeloma

Anti-CD38 monoclonal antibodies have become a pivotal foundation of MM treatment, although intravenous (IV) administration may require prolonged chair time and repeated visits to infusion centers. SC formulations have aided in addressing some of these challenges by shortening administration times while maintaining efficacy.

The isatuximab SC OBI represents a novel approach to SC drug delivery. The device uses a small retractable needle to administer a fixed 1400-mg dose of isatuximab and is the first device-enabled delivery system developed for an oncologic therapy. Previous analyses from the phase 3 IRAKLIA (NCT05405166), phase 2 IZALCO (NCT05704049), and phase 1b TCD15484 (NCT04045795) trials demonstrated efficacy and safety comparable to IV isatuximab, prompting further evaluation of device performance and tolerability.¹

Evaluating Safety and Device Reliability

Researchers performed a cross-trial analysis of patients receiving isatuximab SC OBI across the IRAKLIA, IZALCO, and TCD15484 clinical trials. In total, 349 patients with RRMM received a cumulative 6426 injections of isatuximab administered via the OBI.

Patients in IRAKLIA and the phase 1b trial received isatuximab combined with pomalidomide (Pomalyst; Bristol Myers Squibb) and dexamethasone (Decadron; Pragma Pharmaceuticals), whereas patients enrolled in IZALCO received isatuximab with carfilzomib (Kyprolis; Amgen) and dexamethasone. Investigators assessed injection duration, infusion-related reactions, injection-site reactions, and overall device performance across all studies.

Low Rates of Infusion-Related and Injection-Site Reactions

Across the 6426 administered injections, infusion-related reactions were uncommon. Only 6 were reported, representing 0.09% of all injections and occurring in 4 of 349 patients (1.15%). Most adverse events were grade 1, with a single grade 3 event reported. Notably, no infusion-related reactions resulted in treatment discontinuation.

In the phase 3 IRAKLIA study, nearly one-third of patients ultimately did not require premedication, accounting for more than 900 administered injections. No infusion-related reactions occurred among these patients, suggesting that premedication requirements may be reduced in select individuals following successful treatment initiation.

Injection-site reactions were similarly infrequent. Across all of the trials, 21 patients (6.02%) experienced injection-site reactions, accounting for just 35 events among more than 6400 injections. Most reactions were grade 1 and occurred on the day of treatment administration. Only 2 grade 2 events were reported, and no unexpected local safety concerns emerged.¹

Device Performance Exceeded 99%

One of the most notable findings from the analysis was the reliability of the OBI system. Across all 6426 injections, approximately 99.9% were completed successfully without interruption. Successful administration was achieved in 344 of 349 treated patients, resulting in a patient-level success rate of 98.6%.

Injection times were relatively brief across all studies, with median administration durations ranging from 10 to 13 minutes. These findings suggest that the device can consistently deliver treatment while minimizing time spent receiving therapy.

Potential Implications for Patient-Centered Care

While efficacy was not the focus of this analysis, the findings address an increasingly important aspect of MM treatment: how therapies are delivered. As patients remain on treatment longer and receive multiple lines of therapy over the course of their disease, reducing treatment burden can become an important contributor to quality of life and overall patient satisfaction.

The combination of low rates of infusion-related reactions, minimal injection-site toxicity, and extremely high device reliability suggests that the isatuximab SC OBI could offer a practical alternative to traditional intravenous administration.

Supporting Future At-Home Administration

This cross-trial analysis demonstrated reproducible safety and reliability of subcutaneous isatuximab delivered through an OBI across more than 6400 administered doses.

With over 99.9% of injections successfully completed and very low rates of infusion-related and injection-site reactions, the data support the feasibility of this novel delivery platform and provide an early foundation for future exploration of at-home administration strategies in patients with MM.

REFERENCE

Leleu XP, Cerchione C, Ailawadhi S, et al. Safety and reliability of isatuximab subcutaneous on-body injector: Results across the phase 3 IRAKLIA, phase 2 IZALCO and phase 1b TCD15484 trials. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 7563.