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

Schuster, M.; Zijlstra, J.; Casasnovas, R.O.; Vermaat, J.S.P.; Kalakonda, N.; Goy, A.; ... ; Maerevoet, M. (2022)

Article / Letter to editor

Patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis and a median overall survival of less than 6 months. Outcomes and responses were evaluated in 134 patients with DLBCL administered selinexor. Our findings demonstrate that selinexor treatment in DLBCL patients can safely induce durable responses and improve outcomes regardless of prior treatments and refractory status. 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. (C) 2021 Published by Elsevier Inc.

• Exportin-1
• SINE compounds
• Pretreated
• Relapsed
• Monotherapy
• Refractory
• XPO1

• All authors: Schuster, M.; Zijlstra, J.; Casasnovas, R.O.; Vermaat, J.S.P.; Kalakonda, N.; Goy, A.; Choquet, S.; Neste, E. van den; Hill, B.; Thieblemont, C.; Cavallo, F.; Cruz, F. de la; Kuruvilla, J.; Hamad, N.; Jaeger, U.; Caimi, P.; Gurion, R.; Warzocha, K.; Bakhshi, S.; Sancho, J.M.; Follows, G.; Egyed, M.; Offner, F.; Vassilakopoulos, T.; Samal, P.; Ku, M.; Ma, X.W.; Corona, K.; Chamoun, K.; Shah, J.; Shacham, S.; Kauffman, M.G.; Canales, M.; Maerevoet, M.
• Date: 2022-07-01
• Journal: Clinical Lymphoma, Myeloma and Leukemia
• Volume: 22
• Issue: 7
• Pages: 483 - 494
• DOI: doi:10.1016/j.clml.2021.12.016