Subcutaneous Isatuximab May Optimize Multiple Myeloma Treatment Protocols

Isatuximab-irfc (Sarclisa) delivered subcutaneously via an on-body injector (OBI) exhibited noninferior outcomes vs intravenous isatuximab among patients with multiple myeloma, according to findings from a review of multiple clinical trials presented at the 51st Annual Oncology Nursing Society (ONS) Congress.

Main Data

Subcutaneous isatuximab demonstrated noninferior clinical outcomes and consistent pharmacokinetic parameters compared with standard intravenous administration. In the phase 3 IRAKLIA trial (NCT04505166), which evaluated patients with relapsed/refractory multiple myeloma, the objective response rate (ORR) was similar between the 2 delivery methods. Specifically, the subcutaneous OBI cohort (n = 263) achieved an ORR of 71.1% compared with an ORR of 70.5% in the intravenous cohort (n = 268).

Stratified data demonstrated that flat-dose subcutaneous OBI delivery maintained consistent efficacy across different patient bodyweight subgroups. For individuals weighing 65 kg or less, the ORR was 66% in the subcutaneous OBI arm (n = 85) and 71% in the intravenous arm (n = 84). In the subgroup of patients weighing 66 kg to 85 kg, the ORR was 70% for both the subcutaneous OBI arm (n = 117) and the intravenous arm (n = 118). Among patients weighing more than 85 kg, the ORR was 81% for the subcutaneous OBI arm (n = 62) and 72% for the intravenous arm (n = 65). Pharmacokinetic evidence supported these therapeutic outcomes, showing that subcutaneous OBI therapy achieved noninferiority to intravenous dosing via steady-state trough concentration geometric mean ratios, with acceptable drug exposure across all weight brackets evaluated at cycle 2, day 1.

Study Details

The data within this analysis were synthesized from multiple clinical trials and structured healthcare provider surveys evaluating the safety, reliability, and usability of the subcutaneous OBI system. The primary clinical evidence was drawn from the phase 3 IRAKLIA trial, which directly compared the subcutaneous injector with standard intravenous delivery in patients with relapsed/refractory multiple myeloma. Additional clinical context was derived from the phase 2 IZALCO trial (NCT05704049), which compared the subcutaneous OBI with manual subcutaneous syringe administration in the relapsed or refractory multiple myeloma setting.

Long-term utility data in the front-line setting were drawn from the phase 2 IsaSoCut trial (NCT05889221), which evaluated the subcutaneous OBI configuration specifically for patients with newly diagnosed multiple myeloma who were ineligible for transplant. To supplement these clinical trial findings, researchers integrated experiential data from 2 distinct evaluator groups. The first consisted of a hands-on experience survey of 12 nurses analyzing administration workflows, safety, and patient comfort parameters. The second consisted of an experience survey of 10 nurses documenting changes in clinic resource utilization and patient comfort metrics.

Patient Characteristics

The patient populations represented across the analyzed data sets comprised adults receiving active therapy for plasma cell malignancies. In the phase 3 IRAKLIA trial, patient characteristics were well balanced between the 2 primary treatment arms, with 263 patients randomly assigned to the subcutaneous OBI group and 268 patients randomly assigned to the intravenous group. Weight distribution within this trial population included 169 patients weighing 65 kg or less, 235 patients weighing between 65 kg to 85 kg, and 127 patients weighing more than 85 kg. The operational and qualitative analysis incorporated specific feedback from a cohort of 12 nurses evaluating institutional workflows, a cohort of 10 nurses assessing clinic time impacts, and a combined cohort of 16 nurses and 3 physicians participating within the IZALCO protocol framework.

Main End Points

The primary end points established across these clinical protocols focused on demonstrating the noninferiority of the subcutaneous OBI relative to intravenous administration through ORRs and steady-state trough concentrations. Secondary operational end points evaluated healthcare provider experience, institutional time savings, administration success rates, and patient-reported satisfaction. Among the surveyed nursing cohort (n = 12), 100% reported that the subcutaneous OBI was easy to learn and easy to administer while improving overall workflow efficiency, leading to a universal preference for this system over standard intravenous administration. Furthermore, 90% of these clinicians preferred the OBI over manual subcutaneous delivery with a syringe when administering large-volume antibody formulations.

Comparative workflow assessments demonstrated that nurse action time, patient monitoring requirements, physical effort, and overall time burden were lower with the OBI than with standard intravenous delivery. Data from the separate survey of 10 nurses indicated that 60% observed a reduction in clinic time compared with manual subcutaneous delivery, and 50% reported enhanced patient comfort and decreased anxiety.

In the IZALCO study, 78.9% of healthcare professionals preferred the subcutaneous OBI over manual subcutaneous administration, while 21.1% reported no preference, citing the device's reliability and ease of administration. Technical success end points revealed a high administration success rate, with greater than 99% uninterrupted administrations. The median injection time was 13 minutes, and 97.9% of all subcutaneous OBI administrations were completed within 20 minutes or less.

Patient-centric end points collected by clinicians showed that 100% of nurses noted a complete lack of needle visibility, shortened treatment durations, and better comfort. Additionally, 92% reported that OBI administration decreased patient anxiety relative to intravenous delivery, and 83% described the overall patient experience as generally well-tolerated and painless.

Safety

Safety evaluations across the pooled clinical data indicated that the transition from intravenous delivery to the subcutaneous OBI introduced no new safety signals. Serious treatment-emergent adverse events remained closely aligned with the established safety profiles of known isatuximab-based regimens, and this safety profile was maintained consistently across all evaluated patient bodyweight subgroups. The analysis focused heavily on characterizing systemic infusion reactions and local injection site reactions. Systemic infusion reactions were rare and mild with the subcutaneous OBI, occurring in 1.5% of patients, representing a decline from the 25% infusion reaction rate documented within the intravenous cohort.

Local tissue tolerability was similarly favorable; injection site reactions secondary to subcutaneous OBI delivery were rare and mild, occurring in 4.2% of patients. All reported injection site reactions were classified as grade 1 apart from a single instance that was recorded as a grade 2 event. No severe local tissue reactions were observed in any of the treated cohorts. Furthermore, cross-trial safety comparisons within the IZALCO protocol confirmed low rates of local tissue reactivity, demonstrating similarly low injection site reaction rates between the automated subcutaneous OBI at 0.86% and manual subcutaneous syringe administration at 1.34%.

Reference

Faiman B, Steinback M, Curry N, Barnes Y, Boshar R, Graziano N. An analysis of clinical evidence regarding isatuximab subcutaneous administered via OBI (Isa SC OBI): implications for oncology nurses. Presented at: 51st Annual Oncology Nursing Society (ONS) Congress; May 13-17, 2026; San Antonio, TX. Poster I12.