R-CHOP combined with selinesol is effective in patients with NHL

Researchers evaluated the addition of 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%. Results of the study were presented at the 2020 ASH Annual Meeting.

This open-label Phase Ib study evaluated the safety, tolerability, recommended Phase II dose and maximum tolerated dose (MTD) of selinesol combined with R-CHOP in patients with NHL. The study included 12 patients (median age, 55 years): 10 treatment novices with stage III/IV diffuse large B-cell lymphoma (DLBCL) and 2 patients with follicular lymphoma who were either anthracycline-naïve or had received one prior anthracycline-free therapy.

The study used a standard3+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 60 mg or 80 mg of selinesol (n=6). Maintain selinexol weekly for an additional year at the dose used at the end of R-CHOP.

Grade 3 supraventricular tachycardia and grade 3 syncope occurred in the first three patients treated with selinesol60 mg. No further cardiac events occurred and three patients were added to the cohort. No further serious adverse cardiac events (AEs) occurred. In the first three patients treated with selinesol 80 mg, a dose-limiting toxicity occurred: grade 3 nausea and vomiting.

More patients in the selinesol 80 mg cohort discontinued treatment or had their dose reduced compared withthe 60 mg cohort. Most adverse events were grade 1/2 and included 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 selinexol due to fatigue-related adverse events (with or without nausea). Three patients had dose reductions due to fatigue. Eight patients completed all six cycles of R-CHOP plus selinesol, and six patients continued maintenance therapy. The MTD was not reached, but due to the higher frequency of selinexole discontinuations and dose reductions in the 80 mg cohort, a weekly 60 mg selinexole Phase II dose is recommended.

Effectiveness can be evaluated in 10 patients (6 taking 60 mg and 4 taking 80 mg). After a median follow-up of 476 days, the ORR was 100%, including 9 complete responses and 1 partial response. The researchers noted that a phase II study of R-CHOP plus selinesol is ongoing in first-line DLBCL and Richter's transformation.

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