SELINEXOR IN COMBINATION WITH R‐GDP FOR PATIENTS WITH RELAPSED/REFRACTORY B‐CELL LYMPHOMA: PRELIMINARY RESULTS OF THE SELINDA PHASE IB LYSA STUDY ( EUDRACT NUMBER: 2015‐005612‐15) (2021)

Background: Salvage chemotherapy followed by high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) is the standard treatment of young patients (pts) with relapsed diffuse large B-cell lymphoma (DLBCL). A complete remission before ASCT is the most important prognosis factor for a better outcome. Selinexor is a first-in-class selective inhibitor of nuclear export, which, through inhibition of exportin-1, causes accumulation of tumor suppressor proteins, reduction in oncoproteins and apoptosis. Selinexor has been approved by the US Food and Drug Administration for the treatment of R/R DLBCL, de novo or transformed from follicular lymphoma (FL) pts after ≥2 therapies (Kalakonda 2020). We hereby present preliminary data of a phase IB study (SELINDA study) evaluating the safety and tolerability of Selinexor with R-GDP for pts with B-cell lymphoma after first or second treatment failure. Patients & methods: Eligible pts < 70 years received every 21 days (d) 3 cycles of rituximab 375 mg/m2 on d1, dexamethasone 40 mg on d1 to 4, cisplatin 75 mg/m2 d1 and gemcitabine 1 gr/m2 on d1 and 8 (R-GDP) in combination with escalating doses of Selinexor. The starting dose (dose level 1, DL1) 40 mg was given on days 1, 3, 8, 10 (Cohort A), and from December 2017 on days 1, 8 and 15 (Cohort B). The dose-variation scheme followed a traditional “3+3” design (DL1: 40 mg; DL2: 60 mg), Dose-limiting toxicities (DLTs) were considered during the first cycle. DLTs were defined as non-hematological toxicity grade (Gr) 3-4 excluding alopecia, diarrhea and/or nausea/vomiting and/or fatigue/asthenia, any Gr ≥ 4 hematological toxicity lasting >7 d, any toxicity resulting in a delay of >14 d of the initiation of the second cycle. Results: Between January 2017 and August 2019, 20 pts received Selinexor-R-GDP, 4 pts had FL and, 16 pts had DLBCL. Median age was 63.5 years (range 45-70). In 7 pts of cohort A DL1 (selinexor 40 mg on d1, 3, 8, 10), 1 DLT (anorexia grade 3) was observed and 1 pt discontinued treatment during cycle 3 for intolerance (AE Gr 3 . In 6 pts of cohort B DL1 (selinexor 40 mg on d1, 8, 15), no DLTs were observed; 2 pts discontinued treatment after 2 cycles, 1 for progression and 1 for intolerance (AE + Grade). In 7 pts of cohort B DL2 (selinexor 60 mg on d1, 8, 15), 1 DLT (neutropenia grade 4 >7d) was observed. Fifteen pts experienced one or more adverse events, thrombocytopenia gr 4 (5 in the cohort A 40 mg, 2 in the cohort B 40 mg, 3 in the cohort B 60 mg), neutropenia gr 4, (7 in the cohort A 40 mg, 3 in the cohort B 40 mg, 5 in the cohort B 60 mg). Efficacy results will be reported at the conference. Conclusion : The recommended dose of weekly selinexor in combination with R-GDP was 40 mg on days 1, 8, and 15. The most common adverse events were Gr 1-2 non-hematological or reversible Gr 3-4 thrombocytopenia or neutropenia. Enrollment for the expansion is completed. The research was funded by: Karyopharm. Keywords: Aggressive B-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract M. Maerevoet Consultant or advisory role: Karyopharm O. Casasnovas Consultant or advisory role: Roche, Takeda, MSD, BMS, Gilead Honoraria: Roche, Takeda, MSD, BMS, Gilead Research funding: Roche, Gilead Educational grants: Roche, Amgen G. Cartron Consultant or advisory role: Roche, Celgene Honoraria: Celgene, Roche, Gilead, Sanofi, Abbvie, Novartis, Gilead H. Tilly Consultant or advisory role: Karyopharm