Selinexor Shows Clinical Benefit Across Age Groups in Relapsed/Refractory DLBCL

December 5, 2020 - Selinexor (Xpovio) demonstrated a clinical benefit in patients with relapsed/refractory diffuse large B-cell lymphoma, regardless of age, according to results of a post-hoc analysis of the SADAL trial that were presented during the 2020 ASH Annual Meeting.¹

Findings showed that there was no statistical difference in ORR in patients who were younger than 65 years old (n = 52) vs those who were 65 years and older (n = 82) at 36.5% and 24.4%, respectively (P = .189). The complete response (CR) rates were 17.3% and 11.0%, respectively (P = .431); the partial response (PR) rates were 19.2% in younger patients vs 13.4% with older patients.

The median duration of response (DOR) was 9.7 months in patients younger than age 65 compared with 9.2 months in those who are 65 years and older. Moreover, the incidence of treatment-related adverse events (TRAEs) was similar between the 2 age groups.

“Selinexor is an active, convenient, oral option for patients with relapsed DLBCL, including older patients,” lead study author Marie Maerevoet, MD, in the Department of Hematology at Institut Jules Bordet, said in a virtual poster presentation during the meeting.

Selinexor is a first-in-class, oral selective inhibitor of nuclear export and reactivates tumor suppressor proteins, binding to and inactivating XPO1. In June 2020, the FDA approved selinexor for the treatment of patients with relapsed/refractory DLBCL, de novo or transformed follicular lymphoma, after 2 or more prior therapies, based on earlier findings from the SADAL study.²

In the multicenter, open-label, phase 2b SADAL study, investigators evaluated 60-mg of twice-weekly selinexor monotherapy administered in 28-day cycles in this patient population until disease progression or unacceptable toxicity. The study was initially designed to evaluate selinexor at a 100-mg twice-weekly dose, but this dosage was discontinued in the study protocol in March 2017.³

Eligible patients received at least 2 prior treatments, and had pathologically confirmed de novo DLBCL, or DLBCL transformed from indolent lymphoma.

A total of 134 patients were enrolled. The primary end point was ORR, which was independently assessed by a central imaging committee; secondary end points included overall survival (OS), DOR, and safety.

Patients were evenly split between good prognosis (45%) and poor prognosis (46%) by the Revised-International Prognostic Index (2% were very good and 7% were unknown).

Previously, data showed that selinexor elicited an ORR of 29% (95% CI, 22-38), including a CR rate of 13%, and a 15.7% PR rate. A total 8.2% of patients had stable disease and 62.7% had either progressive disease or were not evaluable.Overall, the median DOR was 9.3 months (95% CI, 4.9–not estimated). The median time to at least a PR was 8.1 weeks (range, 6.7-16.4).

In the post-hoc analysis presented at the 2020 ASH Annual Meeting, investigators sought to determine whether there were differences in efficacy and safety of patients with relapsed/refractory DLBCL when stratified by age: younger than 65 years old (39%) or at least 65 years old (61%)

Baseline characteristics, aside from age, were similar between the 2 cohorts. In the younger age group, the median age was 57 years (range, 35-64) and most patients (84.6%) were between the ages of 51 and 64 years old. A total 61.5% of patients in this cohort were male, and 82.7% of patients had de novo DLBCL. Regarding DLBCL subtypes, patients had germinal center B ([GCB] 53.8%), non-GCB (40.4%), or non-classified disease (5.8%).

In the 65 years and older cohort, the median age was 73 years (range, 65-91) and 40.2% of patients were 75 years and older. A total 57.3% of patients were male, and 73.2% had de novo DLBCL. The DLBCL subtype breakdown was GCB (42.7%), non-GCB (54.9%), and non-classified (2.4%).

The median number of prior therapies was 2 in each age group; 61.5% and 37.8% of patients in the younger and older age groups underwent prior stem cell transplant, respectively.

Results also showed that the median OS was higher in the younger patient group, at 13.7 months compared with 7.8 months in those aged 65 years and older.

The analysis also showed that selinexor is effective in de novo DLBCL, which showed an ORR of 26.2% and in transformed lymphoma (38.7%).

Regarding safety, the TRAEs occurring at 10% or more in either age group were comparable between the 2 arms. Overall, the most common TRAEs were thrombocytopenia, nausea, and fatigue, which can be managed by dose reductions and antiemetic supportive care, Maerevoet said.

Older patients did experience lower rates of thrombocytopenia compared with younger patients (50.0% vs 59.6%, respectively) as well as anemia (30.5% vs 36.5%), but had higher rates of asthenia (18.3% vs 11.5%), nausea (54.9% vs 46.2), vomiting (31.7% vs 17.3%), and decreased weight (26.8% vs 13.5%), which were expected, Maerevoet said.

Selinexor is also approved by the FDA for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.

References

1. Maerevoet M, Schuster MW, Canales MA, et al. Effect of age on the efficacy and safety of single agent oral selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL): a post-hoc analysis from the SADAL pivotal phase 2b study. Presented at: 2020 ASH Annual Meeting & Exposition; December 4-8, 2020; virtual. Abstract 112.
2. FDA approves selinexor for relapsed/refractory diffuse large B-cell lymphoma. News release. FDA. June 22, 2020. Accessed June 22, 2020. bit.ly/37VnEXd.
3. 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 Haem. 2020;7(7):E511-E522. doi:10.1016/S2352-3026(20)30120-4