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A 30-Minute Infusion of Isatuximab Is Safe, Feasible in Patients with Newly Diagnosed Multiple Myeloma
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Key Takeaways
- Isatuximab, a CD38-targeting monoclonal antibody, has shown significant efficacy in improving minimal residual disease rates and progression-free survival in multiple myeloma.
- The phase 1b TCD13983 trial demonstrated the safety and feasibility of a 30-minute isatuximab infusion, reducing the standard 75-minute infusion time.
Isatuximab is a CD38-targeting monoclonal antibody that has demonstrated significant clinical success in improving minimal residual disease rates and progression-free survival.
A 30-minute intravenous infusion of isatuximab (Sarclisa; Sanofi-Aventis U.S. LLC) demonstrates safety and feasibility in patients with newly diagnosed multiple myeloma (NDMM), according to an analysis of study results from the phase 1b TCD13983 trial (NCT02513186).1
Monoclonal antibodies coming out of a syringe | Image Credit: © freshidea - stock.adobe.com
Isatuximab is a CD38-targeting monoclonal antibody that has demonstrated significant clinical success in improving minimal residual disease rates and progression-free survival for patients. Its efficacy and safety in combination therapies have led to multiple FDA approvals. In 2021, isatuximab was approved in combination with carfilzomib (Kyprolis; Onyx Pharmaceuticals) and dexamethasone. Following this, it received another approval in 2024 in combination with bortezomib (Velcade; Millennium/Takeda and Janssen Pharmaceutical Companies), lenalidomide (Revlimid; Bristol Myers Squibb), and dexamethasone, referred to as VRd, based on data from the phase 3 IMROZ trial (NCT03319667).2-5
“Isatuximab is currently administered as an IV infusion,” said study author Enrique M. Ocio, MD, PhD, head of the Hematology Department at the Marqués de Valdecilla University Hospital in Santander, Spain, in an article in ASH Clinical News. “A shorter infusion time represents a major advance for patients and a decrease in workload for oncology institutions. Administering isatuximab in a fixed volume of 250 mL and with increasing speeds of infusion makes it feasible to administer it over 30 minutes as compared to the approximate 75 minutes of the standard infusion.”6
A typical isatuximab 20 mg/mL infusion session takes about 75 minutes, which can incur a heavy time burden for patients. To improve the convenience and comfortability of the treatment, researchers evaluated the safety, tolerability, and feasibility of administering isatuximab in a 30-minute infusion in patients on maintenance therapy in the TCD13983 trial. The study included 45 patients on maintenance treatment between January 2023 and January 2024 who were switched to the 30-minute infusion method and categorized into 3 cohorts: isatuximab plus bortezomib, cyclophosphamide (Cytoxan; Amneal Pharmaceuticals, Inc.), and dexamethasone (Isa-VCd, n=4); isatuximab plus VRd (Isa-VRd)/Part-A (n=13); and Isa-VRd/Part-B (n=28).6,7
The median follow-up for each cohort was 71.7 months, 55.1 months, and 38.1 months in the Isa-VCd, Isa-VRd)/Part-A, and Isa-VRd/Part-B arms, respectively. The median duration of overall treatment exposure was 63.3 (range, 0.2–87.2), 53.9 (0.2–79.5), and 41.5 months (1.4–49.4).6,7
To accelerate the infusions to the target duration of 30 minutes, researchers diluted 10 mg/kg of isatuximab in a 250 mL infusion bag of 0.9% sodium chloride, which was administered for the first infusion at a 250 mL/hour rate for 30 minutes and then at 500 mL/hour for 15 minutes. Subsequent infusions were administered at a rate of 500 mL/hour over 30 minutes for patients who experienced no infusion reactions. The data showed that the median duration of infusion in all patients was 49 minutes at the first infusion (intermediate rate: 31 to 67), 32 minutes at the second infusion (30 to 75), 32 minutes at the third infusion (30 to 80), and 30 minutes at subsequent infusions (23 to 75).6,7
The most common adverse events (AE) during the maintenance phase were arthralgia, hypertension, and upper respiratory tract infection (41.2%) in the Isa-VCd cohort, and diarrhea in the Isa-VRd/Part-A (59.3%) and Isa-VRd/Part-B cohorts (56.5%). After switching to the 30-minute infusion, the most common AEs were upper respiratory tract infections in 50% of patients in the Isa-VCd cohort. In the Isa-VRd/Part-A and Isa-VRd/Part-B (10.7%; 3/28) arms, diarrhea was the most common AE in 38.5% and 10.7% of patients, respectively.6,7
“This way of administration is easy to do and feasible, with only 1 patient out of the 45 who switched presenting with a grade 2 infusion reaction, and it was after this patient had been out of therapy for several months due to a prior adverse event,” Ocio said. “This adverse infusion reaction was adequately managed, and the patient was able to continue with the short administration. This demonstrates the safety of the procedure and indicates that those patients with treatment interruptions should probably restart with the standard infusion before changing to the fast one.”6
Overall, the 30-minute infusion demonstrated safety and tolerability in patients with NDMM, offering patients reduced time in clinics, resulting in a faster, more convenient treatment experience.
