Effect of Prior Therapy and Disease Refractoriness on the Efficacy and Safety of Oral Selinexor in Patients with Diffuse Large B-cell Lymphoma (DLBCL): A Post-hoc Analysis of the SADAL Study.

Abstract

BACKGROUND:

Despite a number of treatment options, patients with diffuse large B-cell lymphoma (DLBCL) whose disease has become refractory to treatment have a poor prognosis. Selinexor is a novel, oral drug that is approved to treat patients with relapsed/refractory DLBCL. In this post hoc analysis of the SADAL study, a multinational, open-label study, we evaluated subpopulations to determine if response to single agent selinexor is impacted by number of lines of prior treatment, autologous stem cell transplant (ASCT), response to first and most recent therapies, and time to progressive disease.

PATIENTS:

Patients (n = 134) with DLBCL after 2-5 prior therapies were enrolled in SADAL and received 60mg selinexor twice weekly.

RESULTS:

The median overall survival was 9.0 months and median progression free survival was 2.6 months. Patients who had the best overall response rate (ORR) and disease control rate were those who had prior ASCT (42.5% and 50.0%) or responded to last line of therapy (35.9% and 43.5%). Patients with primary refractory DLBCL also showed responses (ORR 21.8%). Adverse events between subgroups were similar to the overall study population, the most common being thrombocytopenia (29.1%), fatigue (7.5%), and nausea (6.0%).

CONCLUSION:

Regardless of prior therapy and disease refractory status, selinexor treatment demonstrated results consistent with its novel mechanism of action and lack of cross-resistance. Thus, single agent oral selinexor can induce deep, durable, and tolerable responses in patients with DLBCL who have recurrent disease after several chemoimmunotherapy combination regimens.

• Authors: Michael Schuster, Josée Zijlstra, Rene-Olivier Casasnovas, Joost S P Vermaat, Nagesh Kalakonda, Andre Goy, Sylvain Choquet, Eric Van Den Neste, Brian Hill, Catherine Thieblemont, Federica Cavallo, Fatima De la Cruz, John Kuruvilla, Nada Hamad, Ulrich Jaeger, Paolo Caimi, Ronit Gurion, Krzysztof Warzocha, Sameer Bakhshi, Juan-Manuel Sancho, George Follows, Miklos Egyed, Fritz Offner, Theodoros Vassilakopoulos, Priyanka Samal, Matthew Ku, Xiwen Ma, Kelly Corona, Kamal Chamoun, Jatin Shah, Sharon Shacham, Michael G Kauffman, Miguel Canales, Marie Maerevoet
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 22 Issue 7 Pg. 483-494 (07 2022) ISSN: 2152-2669 [Electronic] United States
• PMID: 35078739 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Hydrazines
• Triazoles
• selinexor

Topics

• Humans
• Hydrazines (adverse effects)
• Lymphoma, Large B-Cell, Diffuse (drug therapy, pathology)
• Lymphoma, Non-Hodgkin (drug therapy)
• Triazoles (adverse effects)