Contributions
Abstract: EP530
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound that blocks XPO1, forcing the nuclear retention and functional activation of tumor suppressor proteins including p53, p73, FOXO, IkB and Rb. The phase 2b SADAL study included 134 patients with relapsed or refractory DLBCL with single agent selinexor twice weekly. The overall response rate (ORR) was 29.1%, median duration of response (DOR) 9.3 months and the median overall survival (OS) 9 months. Based on these data, selinexor was approved by the US FDA for the treatment of relapsed or refractory DLBCL, de novo or transformed from follicular lymphoma. Studies have shown that a lower absolute lymphocyte counts (ALC) is a strong prognostic factor for reduced PFS and OS in patients with DLBCL.
Aims
To performed post-hoc analyses of results from the SADAL study to determine the impact of baseline ALC on the efficacy and safety of selinexor.
Methods
The SADAL study was multi-center, open-label Phase 2b study that enrolled patients with DLBCL treated with 2-5 lines of therapy treated with oral selinexor 60mg twice weekly until disease progression. Patients may have recurrence after stem cell therapy (SCT) or were not candidates for SCT. The primary endpoint was ORR, and other endpoints included DOR, OS and safety assessments. For the current analysis, patients were divided into categories based on baseline ALC (≥1000/µL and <1000/µL) in order to compare outcomes.
Results
Of the 134 patients enrolled in the SADAL study, 61 (46%) had baseline ALC of ≥1000/µL and 71 (53%) had levels <1000/µL. The majority of patients in both groups were <65 years old, 79% and 72%, respectively. In this population, de novo and transformed DLBCL accounted for 82% and 18% with ALC ≥1000/µL and 72% and 28% in patients with ALC <1000/µL and, respectively. DLBCL subtype was also similarly distributed among patients with GCB and non-GCB in those with ALC ≥1000/µL (51% and 43%) and in those with ALC <1000/µL (44% and 55%), respectively.
The ORR in patients who had baseline ALC ≥1000/µL was 32.8% compared to 25.4% for ALC <1000/µL (p=0.455; complete responses (CR) rates were 13.1% vs 14.1% respectively. The median DOR in patients who had ALC ≥1000/µL was 23.0 months compared to 4.9 months in patients with ALC <1000/µL (p=0.228). The median PFS were 3.6 and 2.1 and median OS were 15.5 and 7.6 months in patients with ALC ≥1000/µL and <1000/µL, respectively (p=0.129; p=0.013).
The most common grade ≥3 treatment-related adverse events (AEs) for patients with ALC ≥1000/µL and <1000/µL were thrombocytopenia (42.6% vs. 38.0%), nausea (6.6% vs. 4.2%) and fatigue (9.8% vs. 11.3%). The incidence of treatment-related serious AEs and AEs leading to discontinuation in patients who had a lymphocyte count of ≥1000/µL vs <1000/µL were 26.2% vs. 16.9% and 11.5% vs. 4.2%, respectively; these differences may have been related to duration of response.
Conclusion
In this post-hoc analysis in patients enrolled in SADAL with relapsed/refractory DLBCL treated with single agent oral selinexor, those with baseline ALC ≥1000/µL had a ALC a slightly higher ORR (33% vs 25%) but similar CR rates and PFS to those with ALC<1000/µL. Significantly longer overall survival was observed in patients with higher baseline ALC, and responses in these patients trended to longer duration. While consistent with many reports in the literature regarding the poor prognosis of baseline ALC <1000/µL, these results need to be confirmed in larger studies with longer follow up.
Keyword(s):
Abstract: EP530
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound that blocks XPO1, forcing the nuclear retention and functional activation of tumor suppressor proteins including p53, p73, FOXO, IkB and Rb. The phase 2b SADAL study included 134 patients with relapsed or refractory DLBCL with single agent selinexor twice weekly. The overall response rate (ORR) was 29.1%, median duration of response (DOR) 9.3 months and the median overall survival (OS) 9 months. Based on these data, selinexor was approved by the US FDA for the treatment of relapsed or refractory DLBCL, de novo or transformed from follicular lymphoma. Studies have shown that a lower absolute lymphocyte counts (ALC) is a strong prognostic factor for reduced PFS and OS in patients with DLBCL.
Aims
To performed post-hoc analyses of results from the SADAL study to determine the impact of baseline ALC on the efficacy and safety of selinexor.
Methods
The SADAL study was multi-center, open-label Phase 2b study that enrolled patients with DLBCL treated with 2-5 lines of therapy treated with oral selinexor 60mg twice weekly until disease progression. Patients may have recurrence after stem cell therapy (SCT) or were not candidates for SCT. The primary endpoint was ORR, and other endpoints included DOR, OS and safety assessments. For the current analysis, patients were divided into categories based on baseline ALC (≥1000/µL and <1000/µL) in order to compare outcomes.
Results
Of the 134 patients enrolled in the SADAL study, 61 (46%) had baseline ALC of ≥1000/µL and 71 (53%) had levels <1000/µL. The majority of patients in both groups were <65 years old, 79% and 72%, respectively. In this population, de novo and transformed DLBCL accounted for 82% and 18% with ALC ≥1000/µL and 72% and 28% in patients with ALC <1000/µL and, respectively. DLBCL subtype was also similarly distributed among patients with GCB and non-GCB in those with ALC ≥1000/µL (51% and 43%) and in those with ALC <1000/µL (44% and 55%), respectively.
The ORR in patients who had baseline ALC ≥1000/µL was 32.8% compared to 25.4% for ALC <1000/µL (p=0.455; complete responses (CR) rates were 13.1% vs 14.1% respectively. The median DOR in patients who had ALC ≥1000/µL was 23.0 months compared to 4.9 months in patients with ALC <1000/µL (p=0.228). The median PFS were 3.6 and 2.1 and median OS were 15.5 and 7.6 months in patients with ALC ≥1000/µL and <1000/µL, respectively (p=0.129; p=0.013).
The most common grade ≥3 treatment-related adverse events (AEs) for patients with ALC ≥1000/µL and <1000/µL were thrombocytopenia (42.6% vs. 38.0%), nausea (6.6% vs. 4.2%) and fatigue (9.8% vs. 11.3%). The incidence of treatment-related serious AEs and AEs leading to discontinuation in patients who had a lymphocyte count of ≥1000/µL vs <1000/µL were 26.2% vs. 16.9% and 11.5% vs. 4.2%, respectively; these differences may have been related to duration of response.
Conclusion
In this post-hoc analysis in patients enrolled in SADAL with relapsed/refractory DLBCL treated with single agent oral selinexor, those with baseline ALC ≥1000/µL had a ALC a slightly higher ORR (33% vs 25%) but similar CR rates and PFS to those with ALC<1000/µL. Significantly longer overall survival was observed in patients with higher baseline ALC, and responses in these patients trended to longer duration. While consistent with many reports in the literature regarding the poor prognosis of baseline ALC <1000/µL, these results need to be confirmed in larger studies with longer follow up.
Keyword(s):