Efficacy and safety of ruxolitinib in patients with lower risk myelofibrosis: A single-arm, exploratory and prospective study.

6573 Background: The COMFORT studies assessed the efficacy and safety of ruxolitinib in patients with intermediate-2 and high risk myelofibrosis (MF), and JUMP study has broadened the investigation including patients with intermediate-1 MF in the classification of DIPSS. However, there have been limited prospective studies evaluating the efficacy and safety of patients with low risk MF in the classification of more comprehensive scoring system. Here we present a single-arm, exploratory and prospective study to assess the efficacy and safety of ruxolitinib in patients with lower risk MF in China. Methods: Lower risk was defined as MIPSS-70 ≤ 3, MIPSS+V2.0 ≤ 3, DIPSS-Plus ≤ 1, DIPSS ≤ 2 or MYSEC-PM < 14 according to the expert guidelines. Patients aged ≥ 18 with overt primary myelofibrosis (overt-PMF), prefibrotic primary myelofibrosis (pre-PMF), post-polycythemia vera myelofibrosis (post-PV MF) or post-essential thrombocythemia myelofibrosis (post-ET MF), classified as lower risk were enrolled. The primary endpoint was the proportion of patients with a spleen length reduction of ≥ 50% from baseline at week 48. Secondary endpoints included the best spleen response, the proportion of patients with a ≥ 50% reduction in Total Symptom Score (TSS50) and safety. Results: A total of 40 patients were enrolled in the lower risk group, including 7 pre-PMF, 17 overt-PMF, 8 PPV-MF, and 8 PET-MF patients. The median age was 62.0 years. 32 (80%) were JAK2V617F positive. 16 patients had next generation sequencing (NGS), the most frequent non-driver mutation was in TET2 (43.8%), followed by BCOR (12.5%). By week 48, 26 (65.0%) patients achieved a ≥ 50% decrease in palpable spleen length. 32 (80.0%) patients achieved a ≥ 50% reduction from baseline at any time. The median time to a spleen response was 4.3 weeks. The TSS50 rates at week 48 was 25%. No patients required red blood cell transfusion at baseline. And only 1 patient had a baseline hemoglobin (HB) <100 g/L, which remained stable during the follow-up process. The most common grade ≥ 3 hematological treatment emergent adverse events (TEAEs) were anemia (10.0%) and thrombocytopenia (2.5%). 6 (15.0%) and 15 (37.5%) patients experienced grade 1 or 2 anemia and thrombocytopenia, respectively. The mostly common non-hematological TEAEs was infection (12.5), including upper respiratory tract infection (7.5%), urinary infection (2.5%), fever (2.5%), predominantly of grade 1 or 2. Of note, 1 patient developed staphylococcal sepsis and 1 patient experienced acute renal failure. No one discontinued ruxolitinib treatment due to TEAEs. Conclusions: Ruxolitinib is an effective treatment for patients with intermediate-1 and low risk MF, resulting in improved spleen and symptom responses, along with fewer hematological and non-hematological TEAEs. This trial was registered as ChiCTR2200064250 at ClinicalTrials.gov . Clinical trial information: ChiCTR2200064250.