Home administration of isatuximab subcutaneous by on-body injector in Relapsed/Refractory multiple myeloma in the Phase 3 iraklia study

Abstract

Abstract Introduction: IRAKLIA (NCT05405166) is an ongoing, global, non-inferiority trial of isatuximab (Isa) subcutaneous (SC) administration plus pomalidomide-dexamethasone (Pd), and the first Phase 3 multiple myeloma (MM) trial using an on-body injector (OBI) for SC administration. In IRAKLIA, Isa SC OBI demonstrated non-inferiority in the 2 co-primary endpoints of efficacy and pharmacokinetics compared with Isa intravenous (IV). Significantly more patients expressed higher satisfaction with Isa SC OBI vs Isa IV in IRAKLIA, and more patients and health care providers (HCPs) preferred Isa SC OBI over Isa SC manual push in the Phase 2 IZALCO trial (NCT05704049). The Isa OBI is a wearable, automated injector that adheres to the skin of the abdomen and administers Isa SC with the push of a button without any batteries or electronics. The Isa SC OBI offers hands-free administration; a small, hidden, retractable needle to prevent sharps injury and reduce patient anxiety; low-pressure delivery; a simplified user interface; and flexible administration in either outpatient or home settings. Here, we examine the safety of Isa SC OBI administered by trained nursing professionals during at-home patient visits in IRAKLIA. Methods In IRAKLIA, patients with relapsed/refractory MM (RRMM) aged ≥18 years with ≥1 prior line of therapy (LOT) were randomized 1:1 to Isa SC OBI (1400 mg; n=263) or IV (10 mg/kg; n=264) weekly in Cycle (C)1, then every 2 weeks + P (4 mg/day, Day [D]1–21) + d (40 mg [20 mg if age ≥75 years] weekly) in 4-week cycles. Home administration by a HCP was proposed as an option after 5 cycles for Isa OBI arm patients on D15 from C6 onward, and D1 visits from C6 remained clinic based. Eligibility for home-administration depended on an absence of infusion reactions (IRs) at C4 and C5, hematology test results at D1 of each cycle, investigator judgement, and patient willingness. During at-home visits, providers prepared and applied Isa SC OBI and safely disposed of the device upon completion. Following at-home administration, providers evaluated the injection site for reactions, took vitals, and completed documentation. No specific monitoring was planned after the end of injections. At-home administration was not allowed in some countries due to local regulations. Results In the ongoing IRAKLIA trial, 202 patients were treated with Isa SC OBI within countries where at-home administration was permissible. 11 (5.4%) of these patients from 5 different countries [Australia (n=6), Hungary (n=2), Italy (n=1), Norway (n=1), and Spain (n=1)] have participated in home administration as of the cutoff date (06-Nov-2024), with additional sites and countries initiated after the cutoff date. First at home administrations started at Cycle 6 for the majority of patients (n =7) and at Cycle 7 (n =1), Cycle 8 (n =2), and Cycle 10 (n =1) for the remaining patients. Among the 11 patients participating in at-home visits, more than half switched to at-home administration and have not returned to the hospital for their next Day 15 cycle visit. 55 injections were performed at home. The median injection duration was the same between clinic and at-home administration (13 minutes). Similar to Isa SC OBI use in the clinic, home administration was well tolerated with no new safety signals and a 100% completed injection rate. No at-home Isa OBI administration was omitted or interrupted during the injection. At-home administration had a very low rate of injection-site reactions (ISR; n=1). The single ISR was a Grade 1 episode consisting of injection swelling, which resolved within the same day, and most subsequent Day 15 administrations were performed at home for this patient. No other adverse events (AEs), including no IRs, were linked to at-home visits. No device event linked to at-home visits was reported. Conclusions Initial data from the ongoing IRAKLIA trial support the safety of at-home administration of Isa SC OBI for the treatment of patients with MM. Home administration was well tolerated, with no safety concerns and a median injection time of 13 minutes consistent with in-clinic use of Isa SC OBI. The option of either home or outpatient administration of Isa SC OBI for patients with MM allows for greater flexibility and accessibility of treatment, with the potential to improve patient care and reduce common barriers to patient retention and therapy compliance.