Early Data Demonstrate Selinexor as Safe and Effective Monotherapy in Patients with Myelofibrosis

In previous studies, investigators reported that survival of hematopoietic cells from myelofibrosis (MF) patients positive for the presence of the JAK2 V167F mutation requires exportin 1 (XPO1)-mediated nuclear-cytoplasmic transport. Selinexor is an oral chemotherapy drug that inhibits the growth of malignant cells by blocking XPO1. Selinexor induced hematologic responses in mouse models of myeloproliferative neoplasms, as well as selectively inhibited growth of primary MF cells compared with normal progenitor cells. This study evaluated the effectiveness and safety of selinexor in adult patients with primary or secondary MF who were resistant or intolerant to therapy with JAK inhibitors, including ruxolitinib (RUX). Median duration of previous JAK inhibitor therapy was 22 months (range, 0.5-96 months), and most patients were refractory to RUX at initiation of the study (91.7%). Positivity for high-risk mutations was observed in 8 patients: JAK2 (n = 7), CALR (n = 4), and MPL (n = 1).

All patients (n = 12) in this open-label, prospective trial had platelets >30 K/μL and neutrophils >500 K/μL receiving selinexor once a week (80 mg weekly in the first 6 patients and 60 mg for the 6 remaining patients) with median duration of therapy at 36 weeks (range, 11-114 weeks). Spleen volume was evaluated at weeks 12 and 24, and bone marrow was assessed at baseline and week 24. The primary end point is spleen response at week 24 (≥35% spleen volume reduction [SVR]). Median spleen volume at baseline was 1454 cm3 (range, 835-5792), and SVR was observed above baseline at weeks 12 and 24. At week 12, 9 of 10 evaluable patients demonstrated SVR (≥10% SVR = 6, ≥25% SVR = 3), and 1 patient had early progression. At week 24, a higher degree of SVR was observed among 9 patients (≥25% = 5, ≥35% = 2) compared with baseline. In patients treated with selinexor for >24 weeks (n = 10), SVR ≥25% (n = 6) and SVR ≥35% (n = 4) were observed and occurred at any point during study treatment. One patient became transfusion-independent after 36 weeks of treatment and, at the time of data reporting, has not required transfusion and remains on study treatment. Median overall survival was not reached after a median of 11.1 months (range, 3-30 months) of follow-up, and the 2-year survival rate was 91.7%. Four patients remain on treatment.

Ten patients required dose reduction primarily due to weight loss. The most common treatment-related nonhematologic adverse events were fatigue (grade 1/2, n = 4; grade 3/4, n = 4), weight loss (grade 1/2, n = 3; grade 3/4, n = 1), and dizziness (grade 1/2, n = 3; grade 3/4, n = 2). Among hematologic adverse events, grade 3/4 anemia and thrombocytopenia were observed in 4 and 2 patients, respectively.

In conclusion, selinexor was well-tolerated and achieved sustained SVR in patients with MF who are intolerable to treatment with JAK inhibitors, including RUX. This interim analysis demonstrates selinexor may be a safe and effective therapy in patients with MF, but additional data are needed to further confirm these observations.

Source: Tantravahi SK, Kim SJ, Sundar D, et al. A phase 2 study to evaluate the efficacy and safety of selinexor in patients with myelofibrosis refractory or intolerant to JAK inhibitors. American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 143.

Related Articles

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: