MOMENTUM: momelotinib versus danazol for myelofibrosis patients with anaemia after a prior JAK inhibitor
A JAK inhibitor that also blocks the anaemia-driving ACVR1 pathway improved symptoms and spleen size without worsening, and often improving, anaemia in previously treated patients.
MOMENTUM randomised 195 symptomatic, anaemic patients with myelofibrosis previously treated with a JAK inhibitor to momelotinib or danazol (2:1) for 24 weeks, after which danazol patients could cross over. The primary endpoint was a 50% or greater reduction in total symptom score at week 24. This was achieved by 25% versus 9%; transfusion independence at week 24 was 30% versus 20%, meeting non-inferiority, and spleen volume reduction of at least 35% was 22% versus 3%. Momelotinib inhibits JAK1, JAK2 and ACVR1, the last of which lowers hepcidin and improves iron availability. Grade 3 or higher thrombocytopenia and infections were the main toxicities. The drug was approved in 2023 specifically for myelofibrosis with anaemia.
- 195 JAK-inhibitor-experienced patients with symptomatic myelofibrosis and anaemia; momelotinib vs danazol (2:1).
- Total symptom score reduction of at least 50% at week 24: 25% vs 9%.
- Transfusion independence at week 24: 30% vs 20% (non-inferiority met).
- Spleen volume reduction of at least 35%: 22% vs 3%.
- Mechanism includes ACVR1 inhibition lowering hepcidin, explaining the anaemia benefit.
MOMENTUM addressed the biggest gap left by ruxolitinib: patients whose anaemia makes standard JAK inhibition hard to give. Momelotinib is now the preferred option for anaemic, previously treated myelofibrosis and is being adopted in first line for anaemic patients. The absolute symptom benefit is modest and durable disease modification has not been shown.
- Danazol is a weak comparator with limited efficacy of its own.
- Symptom response rate of 25% is low in absolute terms.
- Short (24-week) randomised period before crossover; long-term comparative data are limited.
- Peripheral neuropathy signal seen in earlier momelotinib trials.
Pages like this
not linked directly; found by shared links- ProductFedratinib
Shares COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis, JAK2, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
- ProductRopeginterferon alfa-2b
Shares JAK2, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
- CompanyIncyte
Shares COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis, Ruxolitinib, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
- InstitutionMays Cancer Center at UT Health San Antonio
Shares Ruxolitinib, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
- Key paperCercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency
- Key paperDostarlimab alone cures mismatch-repair-deficient rectal cancer without surgery or radiotherapy
- PathwayFibroblast activation, desmoplasia & matrix stiffness
Shares Ruxolitinib, JAK2.
- CompanyNovartis
Shares COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis, Ruxolitinib, Myeloproliferative neoplasms (PV, ET, myelofibrosis).