October 14, 2024
Author(s): Courtney Flaherty
Fact checked by: Caroline Seymour
Attempts to leverage drugs that are effective in combination, such as selinexor (Xpovio), as single agents for the management JAK inhibitor–naive myelofibrosis reflects the need for improved personalization of therapy according to individual factors, and mitigation of financial toxicities associated with standard JAK inhibitor–based regimens, according to Joseph M. Scandura, MD, PhD.
Selinexor, an oral exportin 1 inhibitor potentially targeting both JAK/STAT and non-JAK/STAT pathways, has previously demonstrated efficacy when used in combination with ruxolitinib (Jakafi) in the phase 1/3 SENTRY trial (XPORT-MF-034; NCT04562389). Results from the phase 1 portion of the trial showed a 35% or greater reduction in spleen volume (SVR35) at weeks 12 and 24 in 71% and 79% of patients treated with 60 mg of selinexor plus ruxolitinib in the intention-to-treat (ITT) population (n = 14), respectively. Moreover, 58% of patients who achieved symptom improvement of at least 50% (TSS50) at week 24 in the ITT population (n = 12) remained in response at the data cutoff of August 1, 2023.1,2
In July 2023, the FDA granted fast track designation to single-agent selinexorfor the treatment of patients with myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis.3
Selinexor will be evaluated in combination with ruxolitinib in the phase 3 portion of SENTRY,1 and as monotherapy in the phase 2 SENTRY-2 study (XPORT-MF-044; NCT05980806) in JAK inhibitor–naive patients with myelofibrosis.4
“The big thing that differentiates the [SENTRY-2] study is that it’s testing selinexor [alone] and only adding the JAK inhibitor [to selinexor] when it is needed, and it matches the patients’ characteristics. It’s not a one-size-fits-all study,” said Scandura, who is an associate attending physician at NewYork-Presbyterian Hospital and an associate professor of medicine at Weill Cornell Medical College, Cornell University, in New York. “This allows patients to be treated similarly to clinical practice in the context of a clinical trial…and allows us to [learn whether] one of these drugs works much better with selinexor than the other.”
In an interview with OncLive®, Scandura discussed selinexor’s mechanism of action, reviewed clinical data supporting its potential use both alone and in combination with JAK inhibitors in myelofibrosis, and highlighted how approval of this agent as monotherapy could help alleviate financial burdens associated with JAK inhibitor–based regimens.