R-CHOP Plus Selinexor Is Effective in Patients with NHL

Researchers assessed the efficacy of adding selinexor to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with non-Hodgkin lymphoma (NHL) and observed an overall response rate (ORR) of 100%. The results of the study were presented at the 2020 ASH Annual Meeting.

The open-label, phase Ib study assessed the safety, tolerability, recommended phase II dose, and maximum tolerated dose (MTD) of selinexor in combination with R-CHOP in patients with NHL. The study included 12 patients (median age, 55 years): 10 treatment-naïve patients with stage III/IV diffuse large B-cell lymphoma (DLBCL) and two with follicular lymphoma who had received no or one prior therapy not containing an anthracycline.

The study used a standard 3+3 dose escalation design; patients received six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 0.5 mg/kg, prednisone 100 mg) plus selinexor 60 mg (n=6) or 80 mg (n=6). Weekly selinexor maintenance, at the dose employed at the conclusion of R-CHOP, was continued for an additional year.

Among the first three patients receiving selinexor 60 mg, there was an episode of grade 3 supraventricular tachycardia and an episode of grade 3 syncope. No further cardiac events occurred, and this cohort was expanded by three patients. No further serious cardiac adverse events (AEs) occurred. Among the first three patients receiving selinexor 80 mg, one dose-limiting toxicity occurred: grade 3 nausea and vomiting.

More patients in the selinexor 80 mg cohort discontinued treatment or reduced their doses compared with the 60 mg cohort.

The majority of AEs were grade 1/2, including nausea (100%), fatigue (67%), skin and nail changes (58%), constipation (42%), dizziness (42%), sinus congestion (42%), and vomiting (42%); nausea and fatigue lasted approximately one to two days.

Five patients discontinued selinexor due to AEs related to fatigue with or without nausea. Dose reductions occurred in three patients, all due to fatigue. Eight patients completed all six cycles of R-CHOP plus selinexor, and six continued maintenance therapy. The MTD was not reached, but due to the higher frequency of selinexor discontinuation and dose reductions in the 80 mg cohort, selinexor 60 mg weekly is the recommended phase II dose.

Ten patients were evaluable for efficacy (six at 60 mg and four at 80 mg). After a median follow-up of 476 days, the ORR was 100%, including nine complete response and one partial response.

The researchers noted that a phase II study of R-CHOP plus selinexor is ongoing in frontline DLBCL and Richter’s transformation.

Reference

Seymour EK Li Y, Aboukameel A, et al. Selinexor in Combination with R-CHOP for Frontline Treatment of Non-Hodgkin Lymphoma: Results of a Phase 1b Study. Abstract 2109. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, December 2-11, 2020.