Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study

Abstract

Patients with RR DLBCL who have received ≥ 2 lines of therapy have limited treatment options and an expected overall survival (OS) of < 6 months. The SADAL study evaluated single-agent oral selinexor in patients with RR DLBCL and demonstrated an overall response rate (ORR) of 29.1% with median duration of response (DOR) of 9.3 months. The analyses described here evaluated a number of subpopulations in order to understand how response correlates with survival outcomes in order to identify patients who could most optimally benefit from selinexor treatment. Median age was 67 years; 44.8% of patients were ≥ 70 years of age. The median OS was 9.0 months (95% CI 6.2, 13.7) at a median follow-up of 14.8 months. The median OS was not reached in patients with a CR or PR, while patients who did not respond have a median OS of 4.9 months (p < 0.0001). Patients < 70 years had an OS of 11.1 months compared with 7.8 months in patients ≥ 70 years. Among patients with or without prior ASCT, the median OS was 10.9 and 7.8 months, respectively. Among patients with disease refractory to the most recent DLBCL treatment regimen, the median OS was 7.0 months compared with 11.1 months for disease not refractory to the most recent treatment. In a patient population in which survival is expected to be < 6 months, treatment with single-agent oral selinexor was associated with a median survival of 9 months. Increased median OS observed in patients responding to selinexor was consistent across subgroups regardless of age, prior ASCT therapy, or refractory status. Randomized studies of selinexor in combination with a variety of other anti-DLBCL agents are planned. This trial was registered at ClinicalTrials.gov (NCT02227251) on August 28, 2014. https://ichgcp.net/clinical-trials-registry/NCT02227251 .

Keywords: DLBCL; Exportin-1; SINE compounds; Selinexor.

Conflict of interest statement

GF reports personal fees from Karyopharm and Roche, outside the submitted work. R-OC reports grants, personal fees, and non-financial support from Roche, personal fees and non-financial support from Takeda, BMS, Amgen, Janssen, Abbvie, grants and personal fees from Gilead, and personal fees from Merck, outside the submitted work. NK reports research support from Verastem, Gilead, Celgene, and Roche, as well as honoraria from Gilead, Janssen, and Karyopharm. AG reports personal fees and honoraria from AstraZeneca, personal fees and board membership from Cota and Kite/Gilead, personal fees from Janssen, Celgene, Acerta, and research funding from Constellation, Bayer, CALBG, Genentech, Hoffman-La Roche, MD Anderson, Morphosys, Pharmacyclics, and the University of Nebraska, outside the submitted work. BH reports grants and personal fees from Karyopharm, outside the submitted work. FC reports personal fees from Takeda, Gilead, and Janssen, outside the submitted work. JK reports research support from Canadian Cancer Society, Leukemia and Lymphoma Society Canada, Princess Margaret Cancer Foundation, Janssen, Roche, Astra Zeneca, consultation fees from Abbvie, BMS, Gilead, Karyopharm, Merck, Roche, Seattle Genetics, honoraria from Amgen, Antengene, Astra Zeneca, BMS, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics, TG Therapeutics, scientific advisory board member for Lymphoma Canada (Chair) and on the data safety monitoring board for Karyopharm Therapeutics. UJ reports personal fees from Karyopharm, during the conduct of the study; grants and personal fees from AbbVie, Celgene, Gilead, Janssen, Novartis, Roche, Takeda, Amgen, Miltenyi, and BMS, outside the submitted work. JMS reports honoraria from Roche, Janssen, Gilead, Celgene, and Novartis, outside the submitted work. MS reports personal fees from Karyopharm during the conduct of the study, and personal fees from Amgen, Abbvie, Gilead, Takeda, Celgene, Pharmacyclics, Astellas, Verastem, Merck, Novartis, Genentech, and Seattle Genetics, outside the submitted work. TPV reports honoraria from WinMedica, Astellas, and Gilead, honoraria, advisory board membership and research support from Takeda, honoraria and advisory board membership from Roche, Bristol, Genesis, and Novartis, advisory board membership at Janssen, honoraria and research support from Merck and Amgen, and research support from Pfizer and Karyopharm. XM, KC, JS, SS, and MK are employees of Karyopharm. MK and SS are stockholders of Karyopharm. SS holds patents (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents (PCT/US12/048319, 499/2012, PI20102724, and 2012000928) on hydrazide-containing nuclear transport modulators and uses. MC reports personal fees from Celgene, Gilead, Janssen, Karyopharm, Novartis, Roche, Sandoz, and Servier, outside the submitted work. All other authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1

Overall survival by prior regimens and response. Kaplan–Meier curves according to A prior ASCT status; B prior use of lenalidomide; and C response to prior therapy: PR or CR and failure to reach PR or CR