A new clinical trial has found that a 30-minute intravenous (IV) infusion of isatuximab for patients with newly diagnosed multiple myeloma (NDMM) is safe and feasible, providing ease for patients and oncology institutions. The results of the phase Ib study were published in HemaSphere.1
Isatuximab is a CD38-directed cytolytic antibody that is approved by the U.S. Food and Drug Administration for patients with MM, in combination with pomalidomide and dexamethasone for those who have received at least two prior therapies including lenalidomide and a proteasome inhibitor; in combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory (R/R) disease who have received one to three prior lines of therapy; and also in combination with bortezomib, lenalidomide, and dexamethasone for the treatment of adult patients with NDMM who are not eligible for autologous hematopoietic cell transplant. The standard infusion dose of isatuximab is 20 mg/mL, which takes about 75 minutes.
The current trial evaluated a faster 30-minute IV infusion at a 10 mg/kg, 250 mL fixed‐volume infusion to enhance patient and health care provider convenience. The patients on the trial were those with NDMM receiving maintenance isatuximab on a phase I clinical trial that enrolled individuals who were not eligible or not intended for immediate transplantation, who were treated on trial with either isatuximab combined with bortezomib, cyclophosphamide, and dexamethasone (VCD) or bortezomib, lenalidomide, and dexamethasone (VRD).2
“Isatuximab is currently administered as an IV infusion. 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,” said study author Enrique M. Ocio, MD, PhD, head of the Hematology Department at the Marqués de Valdecilla University Hospital in Santander, Spain.
“In our trial, patients were already on the maintenance phase with isatuximab. But I would probably recommend switching to this shorter infusion in clinical practice in those patients with MM who are not having infusion issues within the first one to two cycles,” Dr. Ocio said.
On the study, 45 patients in maintenance treatment between January 2023 and January 2024 were switched to the new 30‐minute infusion method, four who were receiving isatuximab plus VCD and 41 who were receiving isatuximab plus VRD in parts A and B of the trial. The median follow-up was 71.1 months in the VCD cohort, 55.1 months in the VRD part A cohort, and 38.1 months in the VRD part B cohort. The median duration of treatment exposure among these three cohorts was 63.3, 53.9, and 41.5 months, respectively.
To accelerate the infusions to the target infusion duration of 30 minutes, 10 mg/kg isatuximab diluted in a 250 mL infusion bag of 0.9% sodium chloride was administered for the first infusion at an initial 250 mL/hour rate for 30 minutes and then at a rate of 500 mL/hour for 15 minutes. If patients experienced no infusion reactions, the subsequent infusions were to be administered at a rate of 500 mL/hour over 30 minutes.
“This way of administration is easy to do and feasible, with only one 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,” Dr. 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 interruption should probably restart with the standard infusion before changing to the fast one.”
This approach is currently being tested in other trials in the R/R setting to confirm these data. According to Dr. Ocio, a subcutaneous administration of isatuximab via an on-the-body-delivery system is also being developed.
Any conflicts of interest declared by the authors can be found in the original article.
References
- Ocio EM, Perrot A, Moreau P, et al. 30‐minute infusion of isatuximab in patients with newly diagnosed multiple myeloma: results of a phase 1b study. HemaSphere. 2024;8(11):e70041.
- ClinicalTrilas.gov. NCT02513186. Study of isatuximab combined with bortezomib + cyclophosphamide + dexamethasone (VCD) and bortezomib + lenalidomide + dexamethasone (VRD) in newly diagnosed multiple myeloma (MM) non eligible for transplant or no intent for immediate transplantation. January 29, 2024. Accessed December 16, 2024. https://www.clinicaltrials.gov/study/NCT02513186.
