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 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