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
Michael Schuster 1 , Josée Zijlstra 2 , Rene-Olivier Casasnovas 3 , Joost S P Vermaat 4 , Nagesh Kalakonda 5 , Andre Goy 6 , Sylvain Choquet 7 , Eric Van Den Neste 8 , Brian Hill 9 , Catherine Thieblemont 10 , Federica Cavallo 11 , Fatima De la Cruz 12 , John Kuruvilla 13 , Nada Hamad 14 , Ulrich Jaeger 15 , Paolo Caimi 16 , Ronit Gurion 17 , Krzysztof Warzocha 18 , Sameer Bakhshi 19 , Juan-Manuel Sancho 20 , George Follows 21 , Miklos Egyed 22 , Fritz Offner 23 , Theodoros Vassilakopoulos 24 , Priyanka Samal 25 , Matthew Ku 26 , Xiwen Ma 27 , Kelly Corona 27 , Kamal Chamoun 27 , Jatin Shah 27 , Sharon Shacham 27 , Michael G Kauffman 27 , Miguel Canales 28 , Marie Maerevoet 29
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.
CITATION Clin Lymphoma Myeloma Leuk. 2022 Jul;22(7):483-494. doi: 10.1016/j.clml.2021.12.016. Epub 2021 Dec 25.