P1033: jaktinib in patients with myelofibrosis who were refractory or relapsed to ruxolitinib: a single-arm, open-label, multicenter, phase 2 study

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Currently, the only marketed Janus kinase (JAK) inhibitor for the treatment of myelofibrosis in China is Ruxolitinib, which demonstrated symptomatic and splenic benefit despite of exacerbated cytopenias. However, it is reported that at least 50% of patients treated with ruxolitinib could develop resistance or intolerance during the long-term follow up, for whom the life expectancy is largely reduced. There are limited therapeutic options available after ruxolitinib failure. Jaktinib, an oral novel JAK and AVCR1 inhibitor showed promising results in patients with intermediate or high risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Aims: We conducted a phase 2 study to evaluate jaktinib in patients who were refractory or relapsed to prior ruxolitinib therapy. Methods: Patients who had primary, post-polycythemia vera or post-essential thrombocythemia myelofibrosis and were previously treated with ruxolitinib for at least 3 months and with either inadequate efficacy response (defined as <10% spleen volume reduction [SVR] by MRI/CT or <30% decrease in spleen size by palpation from baseline) or spleen regrowth to <10% SVR or <30% decrease in spleen size from baseline following an initial response were recruited to receive jaktinib 100 mg bid. The primary endpoint was the proportion of patients with SVR ≥35% from baseline (SVR35) at week 24, measured by MRI/CT images and assessed by Independent Review Committee. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of patients with ≥50% reduction in Myeloproliterative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), improvement of anemia, safety, etc. Results: A total of 34 patients were enrolled. The median duration of previous ruxolitinib treatment was 18.6 months. The median baseline TSS was 19.5 (range 1-55), hemoglobin was 101.5 g/L (range 61-149), and platelet count was 159×109/L (range 66-951). Patient baseline characteristics are shown in the Table 1.At week 24, 11 (32.4%) patients achieved SVR35. The best spleen response rate was 38.2% (13/34). The median time to achieve the first SVR35 was 8.1 weeks, and the median duration of response was not reached. At week 24, 13 (46.4%) patients achieved a ≥50% improvement in TSS from baseline. Of 16 transfusion-independent patients with hemoglobin ≤100 g/L at baseline, eight (50.0%) had a ≥20 g/L hemoglobin increase by week 24. Of 6 patients who required red blood cell transfusion at baseline, two (33.3%) had a 50% decrease in red blood cell infusion by week 24. The median exposure time of jaktinib was 231 days (range 96-371). Twenty three (67.6%) patients had one or more grade ≥3 treatment emergent adverse events (TEAEs). The most common grade ≥3 TEAEs were anemia (32.4%, n=11), thrombocytopenia (32.4%, n=11), leukocytosis (20.6%, n=7) and leukopenia (11.8%, n=4). A dose reduction or temporary interruption due to TEAEs were reported in 9 (26.5%) patients. Treatment discontinuation due to TEAEs occurred in 2 (5.9%) patients. Summary/Conclusion: Jaktinib is effective and well tolerated in myelofibrosis patients who were refractory/relapsed to ruxolitinib. Jaktinib not only substantially improves splenomegaly, but also reduces myelofibrosis-related symptoms. Therefore, jaktinib could become a new treatment option for those patients failed to ruxolitinib. Keywords: Myelofibrosis, Phase II, Myeloproliferative disorder, Janus Kinase inhibitor