Simple Summary Diffuse large B-cell lymphoma (DLBCL) is a complex disease. A combination of immunotherapy and chemotherapy is used to treat DLBCL at initial diagnosis. Additional treatments are... Show moreSimple Summary Diffuse large B-cell lymphoma (DLBCL) is a complex disease. A combination of immunotherapy and chemotherapy is used to treat DLBCL at initial diagnosis. Additional treatments are available when DLBCL does not respond to initial treatment; however, for many patients, DLBCL will stop responding to treatment (relapse) or may not respond at all (refractory). Selinexor is a novel, oral medication that belongs to a class of drugs called selective inhibitors of nuclear export, and it works by killing cancer cells in patients with DLBCL that has relapsed after or is refractory to at least two treatments. When deciding on a course of treatment, it is useful for physicians to know which frequently described clinical characteristics of DLBCL affect the activity and tolerability of selinexor. We found that selinexor showed similar activity and tolerability across most of the frequently described clinical characteristics assessed. Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients < 65 vs. >= 65 years, and for those with lymphocyte counts >= 1000/mu L vs. < 1000/mu L or lactate dehydrogenase <= ULN vs. > ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL. Show less
Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma.... Show moreAim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p <= 0.05), FACT - General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). Conclusion: In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities.Lay abstractThis work examined quality of life (QoL) among patients with relapsed/refractory diffuse large B-cell lymphoma with two to five prior therapies who received single-agent selinexor in the SADAL clinical trial. Analysis of patient-reported Functional Assessment of Cancer Therapy - Lymphoma and EuroQoL five-dimensions five-levels data showed that patients who had objective clinical response to selinexor maintained their QoL over the course of treatment. Grade >= 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts. Show less
