April 13, 2021
The optimal dose of selinexor in patients with diffuse large B-cell lymphoma (DLBCL) is 60 mg twice weekly, according to a study published online ahead of print in the journal Cancer Chemotherapy and Pharmacology.
“Simulations of the safety and efficacy exposure-response models suggested that, compared to a starting dose of 60 mg twice weekly (BIW), a 40 mg BIW regimen resulted in an absolute decrease in adverse event probabilities between 1.9% and 5.3%, with a clinically significant absolute efficacy decrease of 4.7% in overall response rate,” reported researchers from Karyopharm Therapeutics and Certara.
To determine the optimal selinexor dose in patients with DLBCL, researchers pulled data from seven studies that included 800 patients for a pharmacokinetic analysis, 175 patients for an efficacy analysis, and 322 patients for a safety analysis. Patients in the studies had either DLBCL or other non-Hodgkin's lymphoma (NHL).
Body weight emerged as a significant covariate on clearance and central volume of distribution, while gender was a significant factor on clearance, according to the study.
The overall response rate to selinexor in patients with DLBCL increased with day 1 Cmax, or peak serum concentration after dosing. However, the overall response rate in the patient population decreased with greater tumor size, the study found.
“Significant exposure-safety relationships in NHL patients were identified for the frequency of the following safety endpoints: dose modifications, decreased appetite Grade ≥ 3 (Gr3+), fatigue Gr2+, vision blurred Gr1+, and vomiting Gr2+,” researchers reported. “Similar exposure-safety relationships were found for time-to-onset of the adverse events.”
Xu H, Li H, Wada R, et al. Selinexor population pharmacokinetic and exposure-response analyses to support dose optimization in patients with diffuse large B-cell lymphoma [published online ahead of print, 2021 Mar 26]. Cancer Chemother Pharmacol. 2021;10.1007/s00280-021-04258-6. doi:10.1007/s00280-021-04258-6