Contributions
Abstract: S785
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30
Location: Hall E
Background
Momelotinib (MMB), an investigational oral JAK inhibitor (JAKi), 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 (MF).
Aims
To test the non-inferiority of MMB vs ruxolitinib (RUX) in splenic volume reduction and symptom amelioration, and superiority in transfusion requirement, in JAKi naïve patients with primary myelofibrosis, and post-polycythemia vera or post-essential thrombocythemia myelofibrosis.
Methods
Eligibility included primary myelofibrosis or post-polycythemia vera/essential thrombocythemia myelofibrosis; International Prognostic Scoring System (IPSS) high risk, intermediate-2 risk, or intermediate-1 risk associated with symptomatic splenomegaly; palpable spleen ≥5cm; platelets ≥50 K/μl; no Grade ≥2 peripheral neuropathy. Informed consent was obtained. Stratification was by transfusion dependency and platelets (<100K, 100K-200K, and >200K/μl). Patients were randomized 1:1 to 24 weeks of MMB 200 mg qd + RUX placebo or RUX 20 mg bid (or modified per label) + MMB placebo, after which all patients could receive open label MMB. Assessments: spleen volume by MRI, and patient reported symptoms using a daily eDiary of modified MPN-SAF Total Symptom Score (TSS). The primary endpoint was splenic response rate (SRR; ≥35% reduction in volume from baseline) at 24 weeks. Secondary endpoints, evaluated sequentially at 24 weeks, were rates of TSS response (≥50% reduction from baseline), RBC transfusion independence and RBC transfusion dependence, and rate of RBC transfusion.
Results
175 of 215 (81%) and 201 of 217 (93%) patients randomized to MMB and RUX, respectively, completed the 24 week double blind phase. Efficacy results are shown in the Table below. The most common Grade ≥3 adverse events in the double blind phase with MMB were thrombocytopenia (7%) and anemia (6%), and with RUX were anemia (23%), thrombocytopenia (5%) and neutropenia (5%). Grade ≥3 infections occurred in 7% of MMB and 3% of RUX patients. Treatment emergent peripheral neuropathy occurred in 22 (10%) of MMB (all Grade ≤2) and 10 (5%) of RUX (9 Grade ≤2, 1 Grade 3) patients in the double blind phase, none discontinuing study drug for this problem. Overall, adverse events led to study drug discontinuation in 13% of MMB and 6% of RUX patients in double blind phase.
| Table | |||
| Endpoints | MMB | RUX | p-value |
| Spleen response rate, % | 26.5 | 29.0 | 0.011a |
| TSS response rate, % | 28.4 | 42.2 | 0.98a |
| Transfusion independence rate, % | 66.5 | 49.3 | <0.001b |
| Transfusion dependence rate, % | 30.2 | 40.1 | 0.019b |
| Transfusion rate (units/month), median | 0.0 | 0.4 | <0.001b |
| aTest for non-inferiority; bTest for superiority, all values nominally significant | |||
Conclusion
In patients with JAKi naive myelofibrosis, 24 weeks of momelotinib is non-inferior to ruxolitinib for spleen response but not for symptom response. Momelotinib treatment is associated with a reduced transfusion requirement. NCT01969838
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Janus Kinase inhibitor, Clinical Trial, Myelofibrosis
Abstract: S785
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30
Location: Hall E
Background
Momelotinib (MMB), an investigational oral JAK inhibitor (JAKi), 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 (MF).
Aims
To test the non-inferiority of MMB vs ruxolitinib (RUX) in splenic volume reduction and symptom amelioration, and superiority in transfusion requirement, in JAKi naïve patients with primary myelofibrosis, and post-polycythemia vera or post-essential thrombocythemia myelofibrosis.
Methods
Eligibility included primary myelofibrosis or post-polycythemia vera/essential thrombocythemia myelofibrosis; International Prognostic Scoring System (IPSS) high risk, intermediate-2 risk, or intermediate-1 risk associated with symptomatic splenomegaly; palpable spleen ≥5cm; platelets ≥50 K/μl; no Grade ≥2 peripheral neuropathy. Informed consent was obtained. Stratification was by transfusion dependency and platelets (<100K, 100K-200K, and >200K/μl). Patients were randomized 1:1 to 24 weeks of MMB 200 mg qd + RUX placebo or RUX 20 mg bid (or modified per label) + MMB placebo, after which all patients could receive open label MMB. Assessments: spleen volume by MRI, and patient reported symptoms using a daily eDiary of modified MPN-SAF Total Symptom Score (TSS). The primary endpoint was splenic response rate (SRR; ≥35% reduction in volume from baseline) at 24 weeks. Secondary endpoints, evaluated sequentially at 24 weeks, were rates of TSS response (≥50% reduction from baseline), RBC transfusion independence and RBC transfusion dependence, and rate of RBC transfusion.
Results
175 of 215 (81%) and 201 of 217 (93%) patients randomized to MMB and RUX, respectively, completed the 24 week double blind phase. Efficacy results are shown in the Table below. The most common Grade ≥3 adverse events in the double blind phase with MMB were thrombocytopenia (7%) and anemia (6%), and with RUX were anemia (23%), thrombocytopenia (5%) and neutropenia (5%). Grade ≥3 infections occurred in 7% of MMB and 3% of RUX patients. Treatment emergent peripheral neuropathy occurred in 22 (10%) of MMB (all Grade ≤2) and 10 (5%) of RUX (9 Grade ≤2, 1 Grade 3) patients in the double blind phase, none discontinuing study drug for this problem. Overall, adverse events led to study drug discontinuation in 13% of MMB and 6% of RUX patients in double blind phase.
| Table | |||
| Endpoints | MMB | RUX | p-value |
| Spleen response rate, % | 26.5 | 29.0 | 0.011a |
| TSS response rate, % | 28.4 | 42.2 | 0.98a |
| Transfusion independence rate, % | 66.5 | 49.3 | <0.001b |
| Transfusion dependence rate, % | 30.2 | 40.1 | 0.019b |
| Transfusion rate (units/month), median | 0.0 | 0.4 | <0.001b |
| aTest for non-inferiority; bTest for superiority, all values nominally significant | |||
Conclusion
In patients with JAKi naive myelofibrosis, 24 weeks of momelotinib is non-inferior to ruxolitinib for spleen response but not for symptom response. Momelotinib treatment is associated with a reduced transfusion requirement. NCT01969838
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Janus Kinase inhibitor, Clinical Trial, Myelofibrosis