In the phase IIb SADAL trial reported in The Lancet Haematology, Kalakonda et al found that the oral nuclear export inhibitor selinexor produced durable responses in patients with relapsed or refractory diffuse large B-cell lymphoma. Findings in the trial supported the recent accelerated U.S. Food and Drug Administration approval of selinexor in this setting.

Study Details

Between October 2015 and November 2019, the study enrolled 267 patients from sites in 19 countries who had received two to five lines of previous therapy and whose disease had progressed after or who were not candidates for autologous stem cell transplantation. The trial was initially designed to compare selinexor at 60 mg twice weekly vs 100 mg twice weekly; the 100-mg dose was discontinued when a similar overall response rate and lower adverse event rate was observed at the 60-mg dose in a prespecified interim analysis.

The current analysis includes 127 patients who received selinexor at 60 mg on days 1 and 3 weekly until disease progression or unacceptable toxicity. The primary outcome measure was overall response rate.

Responses

Objective response was observed in 36 patients (28%, 95% confidence interval [CI] = 20.7%–37.0%), with complete response in 15 (12%). An additional 11 patients (9%) had stable disease.

At a median follow-up of 11.1 months, the median duration of response was 9.3 months (95% CI = 4.8–23.0 months), including median durations of 23.0 months (95% CI = 10.4–23.0 months) in patients with complete response and 4.4 months (95% CI = 2.0 months–not evaluable) in patients with partial response. Time to partial response or better occurred at the first radiographic assessment at a median of 8 weeks (range = 7–16 weeks).

Among all patients, at a median follow-up of 14.7 months, median progression-free survival was 2.6 months (95% CI = 1.9–4.0 months) and median overall survival was 9.1 months (95% CI = 6.6–15.1 months). Median overall survival was not reached in patients with objective response and was 18.3 months in those with stable disease.

Adverse Events

The most commonly reported grade 3 or 4 adverse events were thrombocytopenia (in 46% of patients), neutropenia (24%), anemia (22%), fatigue (11%), hyponatremia (8%), and nausea (6%). Febrile neutropenia was observed in 3% of patients. Serious adverse events occurred in 68% of patients, with the most common being pyrexia (7%), pneumonia (5%), sepsis (5%), fatigue (4%), anemia (3%), cardiac failure (3%), and febrile neutropenia (3%). Adverse events led to discontinuation of treatment in 17% of patients. No deaths were considered related to study treatment.

The investigators concluded, “Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory diffuse large B-cell lymphoma who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, noncytotoxic treatment option in this setting.”

Nagesh Kalakonda, MBBS, of the University of Liverpool, is the corresponding author for The Lancet Haematology article.

Disclosure: The study was funded by Karyopharm Therapeutics Inc. For full disclosures of the study authors, visit thelancet.com.