Comparison of the effectiveness and safety of the oral selective inhibitor of nuclear export, selinexor, in diffuse large B cell lymphoma subtypes

Casasnovas, R.O.; Follows, G.; Zijlstra, J.M.; Vermaat, J.S.P.; Kalakonda, N.; Choquet, S.; ... ; Goy, A. (2022)

Article / Letter to editor

The phase 2b, open-label, multicenter SADAL study evaluated single agent oral selinexor, a selective inhibitor of nuclear export (SINE) compound, in patients with diffuse large B cell lymphoma (DLBCL) after >= 2 lines of systemic therapy. Similar activity was observed in GCB- and non-GCB DLBCL with a trend to higher response rates in DLBCL transformed from follicular lymphoma. Lower response rates were observed in double expressor DLBCL; higher response rates were observed in patients with baseline hemoglobin >= 10 g/dL and normal levels of C-MYC or BCL-2 expression (51%). Overall, strong single agent activity with selinexor were observed in patients with relapsed/refractory DLBCL.Background: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Patients and Methods: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. Results: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels >= 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Conclusions: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin. (C) 2021 Elsevier Inc. All rights reserved.

• DLBCL subtypes
• Relapsed/refractory DLBCL
• Treatment response
• XPO1
• Salvage therapy
• De novo and transformed DLBCL

• All authors: Casasnovas, R.O.; Follows, G.; Zijlstra, J.M.; Vermaat, J.S.P.; Kalakonda, N.; Choquet, S.; Neste, E. van den; Hill, B.; Thieblemont, C.; Cavallo, F.; Cruz, F. de la; Kuruvilla, J.; Hamad, N.; Jaeger, U.; Caimi, P.F.; Gurion, R.; Warzocha, K.; Bakhshi, S.; Sancho, J.M.; Schuster, M.; Egyed, M.; Offner, F.; Vassilakopoulos, T.P.; Samal, P.; Ku, M.; Ma, X.W.; Chamoun, K.; Shah, J.; Canales, M.; Maerevoet, M.; Shacham, S.; Kauffman, M.G.; Goy, A.
• Date: 2022-01-01
• Journal: Clinical Lymphoma, Myeloma and Leukemia
• Volume: 22
• Issue: 1
• Pages: 24 - 33
• DOI: doi:10.1016/j.clml.2021.07.017