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Subcutaneous Isatuximab Administration by On-Body Delivery System May Provide a More Convenient Option for Patients with RRMM

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Intravenous (IV) isatuximab (Isa) plus pomalidomide-dexamethasone (Pd) is approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥2 prior lines of therapy. Previous cohorts from a multicenter phase 1b study have confirmed that the safety and efficacy of subcutaneous (SC) Isa, administered by syringe pump, is comparable to IV administration, with a recommended phase 2 dose (RP2D) of 1400 mg. The on-body delivery system (OBDS) mode of administration was developed with the intent of optimizing patient convenience, enhancing patient quality of life, and, with fewer required injections, reducing healthcare costs.

At the 2022 American Society of Clinical Oncology Annual Meeting, Quach and colleagues presented results from an expansion cohort from a multicenter phase 1b study that aimed to evaluate the safety, pharmacokinetics, and efficacy of SC versus IV Isa plus Pd in patients with RRMM who had received ≥2 lines of therapy. In the first cohorts, Isa SC 1000 mg and 1400 mg were administered via a syringe pump. The expansion cohort was later included in which SC Isa 1400 mg was administered via OBDS.

The primary end points were dose-limiting toxicity, injection-site reactions, and pharmacokinetics. Secondary end points included overall response rate (ORR), progression-free survival (PFS), and CD38-receptor occupancy. A total of 56 patients were randomly assigned: 12 patients to Isa IV, 12 to Isa SC 1000 mg, 10 to Isa SC 1400 mg, and 22 to Isa OBDS at the RP2D, in combination with Pd. At data cutoff in January 2022, 4 patients receiving IV Isa, 3 receiving SC 1000 mg, 5 receiving SC 1400 mg, and 19 receiving Isa via OBDS remained on treatment. Median follow-up in IV Isa patients was 20.6 months, and it was 23.8 months in those on SC 1000 mg, 18.1 months in those on SC 1400 mg, and 6.5 months in the OBDS patients.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) were comparable across the cohorts. Grade 3 or 4 TEAEs occurred in 77% of OBDS patients, which is lower than the other cohorts (≥80%) and may be due to shorter follow-up. No patients discontinued Isa due to a TEAE. The most common TEAEs in OBDS patients were neutropenia (77.3%) and anemia (13.6%), and only 1 (4.5%) patient developed febrile neutropenia. Injection-site reactions were reported in ≤10% of patients in each cohort and were all grade 2, occurring at first IV or SC infusion. Of 305 total OBDS administrations, 5 (22.7%) patients experienced 7 injection-site reaction episodes, all of which were grade 1, demonstrating good local tolerability. The median duration of OBDS injection was 10 minutes.

The efficacy of the SC Isa cohorts was comparable to what was observed with IV Isa in the pivotal phase 3 trial, ICARIA. The ORR ranged from 66.7% to 80% across cohorts and was 78.1% in patients treated at the RP2D in the OBDS cohort and 80.0% in the Isa SC RP2D. A very good partial response or better was seen in 40% to 50% of patients across all cohorts. A longer follow-up is needed for the OBDS cohort. The median PFS was 22 months in patients receiving IV Isa and 12.5 months in SC 1000 mg; however, it was not reached in SC 1400 mg and OBDS patients. Pharmacokinetics and CD38 receptor occupancy in OBDS patients was consistent with SC pump patients.

SC Isa by OBDS administration was well-tolerated and may provide a more convenient, less healthcare resource–intensive option for patients with RRMM.

Source

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): interim phase 1b study results. Presented at: American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.

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