Updated results from a phase 1 trial of subcutaneous isatuximab via OBDS continue to demonstrate an excellent local tolerability with comparable efficacy.
Intravenous (IV) isatuximab (Isa) + pomalidomide-dexamethasone (Pd) is approved for use for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥2 previous lines of therapy. Given that pomalidomide and dexamethasone are both administered orally, subcutaneous (SC) delivery of Isa would be ideal to optimize convenience, decrease duration of administration, enhance patient comfort and quality of life, and reduce healthcare cost and resources. Prior results from a phase 1b study determined the recommended phase 2 dose (RP2D) of SC Isa to be 1400 mg, which showed comparable safety and efficacy to IV administration in combination with Pd in patients with RRMM. The on-body delivery system (OBDS), a wearable bolus injector attached to the patient’s abdomen to deliver SC Isa, also demonstrated very good local tolerability. Quach and colleagues reported updated results from the phase 1b trial and expansion cohort.
The multicenter, open-label, phase 1b study aimed to evaluate the safety, pharmacokinetics, and efficacy of SC versus IV Isa + Pd in pretreated RRMM after 2 or more lines of therapy. Fifty-six patients were randomized and treated: 12 patients to Isa IV, 12 to Isa SC by infusion pump (IP) at 1000 mg (IP1000), 10 to Isa IP at 1400 mg (IP1400), and 22 to Isa OBDS at the RP2D, all in combination with Pd. As of May 2022, 33% IV, 25% IP1000, 30% IP1400, and 59% OBDS patients were still on treatment. Median follow-up was 24 months in IV patients, 29 months in IP1000 patients, 23 months in IP1400 patients, and 10 months in OBDS patients. Treatment-related grade 3 or 4 treatment-emergent adverse events occurred in 83.3% of IV patients, 91.7% of IP1000 patients, 80% of IP1400 patients, and 81.8% of OBDS patients. Grade ≥3 infections were reported in 25%, 25%, 40%, and 36.4% of IV, IP1000, IP1400, and OBDS cohorts, respectively. Two deaths occurred in the OBDS cohort, 1 unrelated to treatment and 1 due to bacterial meningitis related to treatment. Infusion reactions were infrequent, and there was excellent tolerability with OBDS; 5 patients experienced 7 injection-site reactions, all of which were grade 1. The overall response rate was 66.7%, 66.7%, 80%, and 72.7% in the IV, IP1000, IP1400, and OBDS cohorts, respectively. Complete response rates or better were 16.7% in the IV cohort, 25% in the IP1000 cohort, 20% in the IP1400 cohort, and 22.7% in the OBDS cohort. Minimal residual disease (MRD) negativity was observed in 83% of IV patients, 20% of IP1400 patients, and 9.1% of OBDS patients; MRD negativity rate at the RP2D was 12.5%.
Updated results continue to show a tolerable safety profile and comparable efficacy with OBDS administration of Isa, which may provide a more convenient option for patients. A non-inferiority trial of Isa SC with OBDS versus Isa IV in combination with Pd is ongoing.
Reference
- Quach H, Parmar G, Ocio EM, et al. Subcutaneous (SC) isatuximab administration by an on-body delivery system (OBDS) in combination with pomalidomide-dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM): phase 1b expansion study results. Poster Presented at: 2022 American Hematology Society Annual Meeting; December 10-13; New Orleans, LA. Abstract 1923.