Subcutaneous Isatuximab Regimens Show Efficacy in R/R Multiple Myeloma

Combining isatuximab-irfc (Sarclisa) with carfilzomib (Kyprolis) and dexamethasone (Kd) appeared to confer efficacy and safety among patients with relapsed/refractory multiple myeloma regardless of subcutaneous administration via on-body injector (OBI) or manual injection, according to data from the phase 2 IZALCO study (NCT05704049) published in Blood Cancer Journal.¹

With a median follow-up of 10.1 months, data showed an objective response rate (ORR) of 79.7% among all patients (n = 74), with 62.2% achieving a very good partial response (VGPR) or better. Among patients assigned to receive treatment via manual injections or OBI administration, respectively, the ORRs were 81.0% and 79.2% and the VGPR or better rates were 66.7% and 62.5%.

Treatment produced a median time to first response of 1.05 months (95% CI, 0.986-1.216) and a median time to best response of 3.81 months (95% CI, 2.825-4.632). The estimated median progression-free survival (PFS) was not reached (NR; 95% CI, 13.14-NR), although data were immature at the time of analysis.

Questionnaire responses revealed that 74.5% of treated patients preferred treatment via OBI administration vs 17% who preferred a manual injection (P = .0004); 8.5% expressed no preference for either method. Among 19 health care providers—including 16 nurses and 3 physicians—78.9% reported a preference for OBI administration vs 21.1% who had no preference for either modality; none preferred manual injections.

“In conclusion, our study findings with [subcutaneous] isatuximab plus Kd are consistent with the results of the intravenous isatuximab plus Kd arm of IKEMA [NCT03275285], with no new safety signals besides a few low-grade [injection site reactions] associated with the [subcutaneous] administration route and a substantially lower rate of [infusion reactions],” lead study author Gurdeep Parmar, MD, MBBS, FRCPA, FRACP, from Illawarra Cancer Care Centre at Wollongong Hospital of the University of Wollongong, wrote with coauthors in the publication.^1,2 “No impact of the [subcutaneous] delivery method—OBI or manual injection—was observed on the efficacy, safety, [pharmacokinetics], and immunogenicity of isatuximab given [subcutaneously] in combination with Kd to patients with [relapsed/refractory multiple myeloma], supporting the feasibility of using the OBI as a convenient and preferred method for isatuximab [subcutaneous] administration across treatment regimens.”

In the sequential, open-label phase 2 IZALCO study, patients were assigned to receive isatuximab at a flat dose of 1400 mg subcutaneously; intravenous carfilzomib at 20 mg/m² on days 1 to 2 and 56 mg/m² on days 8 to 9 and 15 to 16 in cycle 1 plus days 1 to 2, 8 to 9, and 15 to 16 of subsequent cycles; and intravenous or oral dexamethasone at 20 mg on days 1 to 2, 8 to 9, 15 to 16, and 22 to 23. Additionally, investigators gave isatuximab via manual subcutaneous administration with a commercially available syringe and butterfly infusion set for 42 patients whereas 24 began with treatment via OBI administration in the periumbilical region.

ORR was a primary efficacy end point. Secondary end points included infusion reactions, injection site reactions, duration of response, time to first response, time to best response, PFS, and overall survival.³ Patients 18 years or older with relapsed/refractory multiple myeloma, measurable disease, at least 1 prior line of antimyeloma treatment, and adequate hematologic, renal, and liver function were eligible for enrollment in the trial.

The median patient age was 65.0 years (range, 44-85), and most had International Staging System stage I disease at entry (56.8%). Additionally, most patients had bone disease (78.4%), and 45.9% had disease refractory to an immunomodulatory drug, 41.9% to a proteasome inhibitor, and 18.9% to both types of agents. The median number of prior lines of antimyeloma treatments was 1 (range, 1-5).

Treatment-emergent adverse effects (TEAEs) of any grade occurred in 93.2% of patients, 54.1% experienced grade 3 or higher TEAEs, and 35.1% had treatment-related grade 3 or higher TEAEs. The most common any-grade TEAEs included upper respiratory tract infection (37.8%), pneumonia (16.2%), hypertension (13.5%), COVID-19 (12.2%), insomnia (12.2%), diarrhea (10.8%), and pyrexia (10.8%).

Infusion reaction episodes occurred in 2 patients (2.7%) who underwent manual injection; no infusion reactions were reported among those who received OBI administration. Data showed comparable rates of infusion site reactions with manual injections (1.34%) and OBI administration (0.86%), with no interruptions in subcutaneous isatuximab treatment.

References

1. Parmar G, Capra M, Seguro F, et al. Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the phase 2 study IZALCO. Blood Cancer J. Published online December 27, 2025. doi:10.1038/s41408-025-01436-0
2. Moreau P, Dimopoulos MA, Mikhael J, et al; IKEMA Study Group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4
3. A study to investigate subcutaneous isatuximab in combination with carfilzomib and dexamethasone in adult participants with relapsed and/​or refractory multiple myeloma (IZALCO). ClinicalTrials.gov. Updated December 29, 2025. Accessed January 5, 2026. https://tinyurl.com/2tawdvw3