Scientific publications

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

Jul 1, 2022 | Magazine: Clinical Lymphoma, Myeloma & Leukemia

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. 

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