A Phase 1 study published in Scientific Reports investigated the pharmacokinetics, safety, and preliminary efficacy of isatuximab monotherapy in Chinese patients with relapsed/refractory multiple myeloma (RRMM). The multi-center, open-label, single-arm trial (NCT03733717) administered isatuximab intravenously at 20 mg/kg weekly during the first cycle, followed by bi-weekly administrations in subsequent cycles. This study addresses the need for evaluating drug behavior in diverse populations, ensuring treatment strategies are effective and safe across different ethnicities.
Study Design and Patient Population
The study enrolled adult patients with symptomatic MM who had received at least two prior lines of anti-myeloma treatment, including an IMiD drug or PI. Patients had to be refractory to the most recently received IMiD or PI-based therapy. Key exclusion criteria included ECOG PS > 2, life expectancy < 3 months, and prior treatment with any anti-CD38 agent. Premedications, including methylprednisolone, diphenhydramine, ranitidine, and acetaminophen, were administered to mitigate infusion reactions.
Pharmacokinetic and Immunogenicity Assessments
Pharmacokinetic (PK) analyses were conducted using blood samples collected at various time points. Functional isatuximab levels were measured using a Gyrolab immunoassay. The PK parameters, including Ceoi, Cmax, and AUCtau, were analyzed using non-compartmental analysis. Immunogenicity was assessed by measuring anti-drug antibodies (ADA) using a validated PandA method.
Safety and Efficacy Outcomes
Adverse events (AEs) were monitored and graded using the NCI-CTCAE version 4.03. Best overall responses were evaluated according to the IMWG uniform response criteria. The overall response rate (ORR) was defined as the proportion of patients achieving stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).
Key Findings
The study included 20 evaluable Chinese patients. The pharmacokinetic profile of isatuximab in Chinese RRMM patients was found to be consistent with that observed in global studies. The safety profile was also deemed manageable, with AEs monitored and graded. Preliminary anti-myeloma activity was observed based on IMWG criteria. These findings support the global development and application of isatuximab in treating RRMM, demonstrating its consistent behavior across different ethnic groups.
Implications for RRMM Treatment
Multiple myeloma remains a challenging malignancy, particularly in relapsed/refractory settings. Isatuximab, a CD38-directed antibody, has shown promise in combination therapies. This study provides valuable data on its use as a monotherapy in a Chinese patient population, contributing to the growing body of evidence supporting its efficacy and safety. Further studies are warranted to explore isatuximab's potential in combination regimens and to optimize treatment strategies for RRMM patients worldwide.
