For patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatment with selinexor resulted in efficacy and a manageable adverse event (AE) profile, according to clinical trial results published in The Lancet Haematology.
In this open-label, single-arm phase 2b SADAL study (ClinicalTrials.gov Identifier: NCT02227251), patients with R/R DLBCL were administered either twice-weekly 60 mg or 100 mg of selinexor, an oral noncytotoxic treatment. Enrolled patients had been previously treated with 2 to 5 prior therapies, and autologous stem cell transplantation was not an option. The primary outcome was overall response rate (ORR). Safety and ORR were evaluated in patients who were administered 60 mg of selinexor.
A total of 127 patients were evaluated. The ORR was 28% (95% CI, 20.7-37.0), the rate of complete response was 12%, and partial response was achieved in 17% of patients. Patients with DLBCL of germinal center B-cell (GCB) subtype had an ORR of 34%, and those with non-GCB subtype had an ORR of 21%.
For a subgroup of patients with high levels of the biomarker c-Myc, the ORR was 13%, while those with low levels of c-Myc had an ORR of 42% (P =.0024). Similar patterns were noted for patients based on double or triple expresser status, but these patterns were mainly attributed to c-Myc expression status.
Median progression-free survival time was 2.6 months, with a median overall survival (OS) time of 9.1 months. These were assessed at a median follow-up of 14.7 months.
The most common grade 3 to 4 AE was thrombocytopenia, which was reported in 46% of patients. Other common grade 3 to 4 AEs were neutropenia (24% of patients) and anemia (22% of patients). Serious AEs were reported in 48% of patients and most commonly included pyrexia (7% of patients), pneumonia (5% of patients), and sepsis (5% of patients). The mortality rate was 58%, although investigators reported that none of the mortalities were associated with selinexor.
Discontinuations related to treatment-emergent AEs were reported in 17% of patients, and treatment-emergent AEs led to dose modifications in 70% of patients.
“Because of the poor prognosis of patients with relapsed or refractory DLBCL after at least two previous regimens, the limitations of available therapeutic interventions, and the ageing population, single-drug selinexor administered in the out-patient setting showed meaningful durable anti-DLBCL activity.”
The researchers concluded that survival outcomes were associated with response to selinexor and suggested that exportin 1 inhibition may be useful in treatment of R/R DLBCL.
Disclosure: Some of the authors disclosed financial relationships with pharmaceutical companies and medical device manufacturers. For a full list of disclosures, please refer to the original study.
Kalakonda N, Maerevoet M, Cavallo F, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7(7):e511-e522.