Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export, Selinexor, in Diffuse Large B Cell Lymphoma Subtypes.

Abstract Background The SADAL study evaluated oral selinexor in patients with relapsed/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. Microabstract 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.