Contributions
Abstract: S786
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:30 - 08:45
Location: Hall E
Background
Momelotinib (MMB), an investigational oral JAK inhibitor, has been shown in early trials to reduce spleen volume, improve disease associated symptoms and improve red blood cell (RBC) transfusion requirements in patients with myelofibrosis.
Aims
Test the superiority of MMB versus best available therapy (BAT) in splenic volume reduction, symptom amelioration, and transfusion requirement at 24 weeks in patients with primary myelofibrosis (PMF), post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/ET MF) who were previously treated with ruxolitinib.
Methods
Eligibility included PMF or post-PV/ET MF; Dynamic International Prognostic Scoring System (DIPSS) high risk or intermediate-2 risk, or intermediate-1 risk associated with symptomatic splenomegaly; currently or previously treated with ruxolitinib for at least 28 days who either required transfusions or dose reduction to <20 mg BID with at least one of Grade ≥3 thrombocytopenia, anemia, or bleed; palpable spleen ≥5cm; and no Grade ≥2 peripheral neuropathy. Informed consent was obtained. Stratification was by transfusion dependency and baseline TSS (modified MPN-SAF Total Symptom Score) <18 or ≥18. Patients were randomized 2:1 to 24 weeks of open-label MMB 200 mg QD or BAT. Assessments included spleen volume by MRI, and patient-reported symptoms using a daily eDiary for TSS. Primary endpoint was splenic response rate at 24 weeks (SRR24; ≥35% reduction in volume from baseline). Secondary endpoints, evaluated sequentially, were rates of TSS response (TSS RR; ≥50% reduction from baseline), RBC transfusion, RBC transfusion independence (TI) and RBC transfusion dependence (TD).
Results
73 of 104 (70%) and 40 of 52 (77%) patients receiving MMB or BAT, respectively, completed the 24 week randomized treatment phase. BAT for 88% of patients included ruxolitinib, and 27% of patients were on ruxolitinib in combination with other drugs. Efficacy results are in Table. The most common treatment-emergent adverse events in MMB patients were diarrhea (33%), asthenia (19%), nausea (19%), and cough (17%), and in BAT patients, asthenia (21%), fatigue (19%), anemia (15%), diarrhea (15%), and abdominal pain (15%); the most common Grade ≥3 adverse events in MMB patients were anemia (13%) and thrombocytopenia (7%), and in BAT patients, anemia (13%), thrombocytopenia (6%) and abdominal pain (6%). Treatment emergent peripheral neuropathy occurred in 11 (11%) of MMB (1 Grade 3) and in no BAT patients; MMB was discontinued in 3 patients due to neuropathy.
| Table | |||
| Endpoints | MMB | BAT | p-value |
| SRR, % | 6.7 | 5.8 | 0.90 |
| TSS RR, % | 26.2 | 5.9 | <0.001a |
| Transfusion rate (units/month), median | 0.5 | 1.2 | 0.39 |
| TI rate, % | 43.3 | 21.2 | 0.001a |
| TD rate, % | 50.0 | 63.5 | 0.10 |
| ap-values nominally significant | |||
Conclusion
In previously ruxolitinib-treated patients with myelofibrosis, 24 weeks of momelotinib was not superior to best available therapy for splenic response, but significantly better in improving disease related symptoms and transfusion independence. NCT02101268
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Phase III, Myelofibrosis, Janus Kinase inhibitor, Clinical Trial
Abstract: S786
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:30 - 08:45
Location: Hall E
Background
Momelotinib (MMB), an investigational oral JAK inhibitor, has been shown in early trials to reduce spleen volume, improve disease associated symptoms and improve red blood cell (RBC) transfusion requirements in patients with myelofibrosis.
Aims
Test the superiority of MMB versus best available therapy (BAT) in splenic volume reduction, symptom amelioration, and transfusion requirement at 24 weeks in patients with primary myelofibrosis (PMF), post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/ET MF) who were previously treated with ruxolitinib.
Methods
Eligibility included PMF or post-PV/ET MF; Dynamic International Prognostic Scoring System (DIPSS) high risk or intermediate-2 risk, or intermediate-1 risk associated with symptomatic splenomegaly; currently or previously treated with ruxolitinib for at least 28 days who either required transfusions or dose reduction to <20 mg BID with at least one of Grade ≥3 thrombocytopenia, anemia, or bleed; palpable spleen ≥5cm; and no Grade ≥2 peripheral neuropathy. Informed consent was obtained. Stratification was by transfusion dependency and baseline TSS (modified MPN-SAF Total Symptom Score) <18 or ≥18. Patients were randomized 2:1 to 24 weeks of open-label MMB 200 mg QD or BAT. Assessments included spleen volume by MRI, and patient-reported symptoms using a daily eDiary for TSS. Primary endpoint was splenic response rate at 24 weeks (SRR24; ≥35% reduction in volume from baseline). Secondary endpoints, evaluated sequentially, were rates of TSS response (TSS RR; ≥50% reduction from baseline), RBC transfusion, RBC transfusion independence (TI) and RBC transfusion dependence (TD).
Results
73 of 104 (70%) and 40 of 52 (77%) patients receiving MMB or BAT, respectively, completed the 24 week randomized treatment phase. BAT for 88% of patients included ruxolitinib, and 27% of patients were on ruxolitinib in combination with other drugs. Efficacy results are in Table. The most common treatment-emergent adverse events in MMB patients were diarrhea (33%), asthenia (19%), nausea (19%), and cough (17%), and in BAT patients, asthenia (21%), fatigue (19%), anemia (15%), diarrhea (15%), and abdominal pain (15%); the most common Grade ≥3 adverse events in MMB patients were anemia (13%) and thrombocytopenia (7%), and in BAT patients, anemia (13%), thrombocytopenia (6%) and abdominal pain (6%). Treatment emergent peripheral neuropathy occurred in 11 (11%) of MMB (1 Grade 3) and in no BAT patients; MMB was discontinued in 3 patients due to neuropathy.
| Table | |||
| Endpoints | MMB | BAT | p-value |
| SRR, % | 6.7 | 5.8 | 0.90 |
| TSS RR, % | 26.2 | 5.9 | <0.001a |
| Transfusion rate (units/month), median | 0.5 | 1.2 | 0.39 |
| TI rate, % | 43.3 | 21.2 | 0.001a |
| TD rate, % | 50.0 | 63.5 | 0.10 |
| ap-values nominally significant | |||
Conclusion
In previously ruxolitinib-treated patients with myelofibrosis, 24 weeks of momelotinib was not superior to best available therapy for splenic response, but significantly better in improving disease related symptoms and transfusion independence. NCT02101268
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Phase III, Myelofibrosis, Janus Kinase inhibitor, Clinical Trial