Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single‐arm, open‐label, phase 2, multicenter study

Abstract

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib‐intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF‐related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non‐100 mg bid doses (non‐100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%–57.8%). There were 41.9% (13/31) of transfusion‐independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment‐emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.

ACVR1: A Novel Therapeutic Target to Treat Anemia in Myelofibrosis

“…These results were associated with an increase in Hb levels ≥2 g/dL from baseline in 35.6% (21/59) of the patients with Hb ≤ 10 g/dL [91]. In the phase 2b trial enrolling MF patients intolerant to ruxolitinib, 13 (42%) of 31 patients with baseline Hb ≤ 10 g/dL reported ≥20 g/dL Hb increase, and 11 (58%) of 19 TD patients had a 50% reduction in the frequency of RBC transfusions (1 patient became TI) [92]. An interim analysis of the data from the phase 3 trial (NCT04617028) evidenced that 71% of the jaktinib-treated TD patients and 40% of the hydroxyurea-treated TD patients achieved a ≥50% decrease in RBC transfusions by week 24, and one patient achieved TI in the jaktinib arm.…”

Jaktinib and momelotinib for the treatment of myelofibrosis—Birds of a feather?

“…Taken together, it is clear that jaktinib is therapeutically active in ruxolitinib‐naïve, intolerant, or relapsed/refractory MF 26–28 . It also seems apparent that the drug has efficacy, and safety profile that is similar to that of momelotinib, which is not surprising considering their common chemical structure, save for differences in kinetic isotope effect.…”

“…In the current edition of AJH , Zhang et al have followed up on their above‐described study, 26 this time focusing on ruxolitinib‐intolerant ( n = 51) 27 or ruxolitinib‐relapsed/refractory ( n = 34) 27 MF. Among the ruxolitinib‐intolerant group (median follow‐up 10.7 months), 27 44 patients were evaluable for efficacy on jaktinib 100 mg BID dosing; at week 24, SVR35 was 43.2%, anemia response in patients who were not transfusion‐dependent but with baseline hemoglobin <10 g/dL was 41.9%, and symptom response was 61.8%; treatment‐emergent adverse events included thrombocytopenia (22.2% grade ≥3), neutropenia (15.6% grade ≥3), increased serum creatinine (22.2% grade ≤2), increased bilirubin (2.2% grade ≤2), increased transaminase (17.8% grade ≤2), and shingles (any grade 11%).…”

“…In the current edition of AJH , Zhang et al have followed up on their above‐described study, 26 this time focusing on ruxolitinib‐intolerant ( n = 51) 27 or ruxolitinib‐relapsed/refractory ( n = 34) 27 MF. Among the ruxolitinib‐intolerant group (median follow‐up 10.7 months), 27 44 patients were evaluable for efficacy on jaktinib 100 mg BID dosing; at week 24, SVR35 was 43.2%, anemia response in patients who were not transfusion‐dependent but with baseline hemoglobin <10 g/dL was 41.9%, and symptom response was 61.8%; treatment‐emergent adverse events included thrombocytopenia (22.2% grade ≥3), neutropenia (15.6% grade ≥3), increased serum creatinine (22.2% grade ≤2), increased bilirubin (2.2% grade ≤2), increased transaminase (17.8% grade ≤2), and shingles (any grade 11%). All the patients in the ruxolitinib‐relapsed/refractory group ( n = 34) received jaktinib 100 mg BID (median follow‐up 7.2 months); at week 24, SVR35 was 32.4%, anemia response in patients who were not transfusion‐dependent but with baseline hemoglobin <10 g/dL was 50%, and symptom response was 46.4%; treatment‐emergent adverse events included thrombocytopenia (32.4% grade ≥3), neutropenia (8.8% grade ≥3), increased serum creatinine (15.6% grade ≤2), increased bilirubin (32.4 grade ≤2), and increased transaminase (20.6% grade ≤2).…”