MOMELOTINIB TAB

Clinical Criteria Summary

Uncontrolled active infection
Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis
Untreated HIV infection
At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Unmanageable drug interaction
Inability to swallow tablets whole
Pregnancy unless expected benefits to the mother outweigh potential risks to the fetus
Lactating

Prescribed and monitored by a VA / VA Community Care hematologist / oncologist
Goals of care and role of Palliative Care consult have been discussed and documented
Symptomatic intermediate or high-risk myelofibrosis (primary or secondary post-polycythemia vera or post-essential thrombocythemia)
Currently no plan for allogeneic hematopoietic stem cell transplant
Splenomegaly by palpation (≥ 5 cm below the costal margin) or imaging
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Completed hepatitis B screening (HBsAg, anti-HBc, and anti-HBs)
Current or past completion of hepatitis C screening

Myelofibrosis-associated anemia (hemoglobin < 10 g/dL) with symptomatic splenomegaly or constitutional symptoms, where primary reason for treatment is anemia
Myelofibrosis-associated anemia (hemoglobin < 10 g/dL) without symptomatic splenomegaly or constitutional symptoms, following a prior trial of one non-Janus kinase inhibitor (non-JAKI) treatment
Splenomegaly or symptoms with platelet count < 50 × 10^9/L as primary reason for treatment, following a prior trial of pacritinib unless medically inadvisable
Splenomegaly or symptoms with platelet count ≥ 50 × 10^9/L, following a prior trial of ruxolitinib unless medically inadvisable (e.g., pre-existing severe anemia [hemoglobin < 8 g/dL] or thrombocytopenia with platelets < 50 × 10^9/L)
Persistent grade 3 anemia (hemoglobin < 8.0 g/dL) despite ruxolitinib dosage reductions

HBsAg-negative but anti-HBc-positive: Requires consultation with GI/liver or infectious diseases expert for antiviral prophylaxis vs preemptive monitoring for HBV reactivation
Concomitant kinase inhibitor use: Must be discontinued per its prescribing information
Uncontrolled acute or chronic liver disease: Treatment delayed until causes investigated and treated
Severe liver impairment (Child-Pugh Class C): Initial dosage reduced to 150 mg once daily
Concomitant BCRP substrate use: Dose decreased per prescribing information (e.g., rosuvastatin initially 5 mg once daily, max 10 mg daily)
Patients who can become pregnant or have partners who can become pregnant: Counseling on risks vs benefits and use of effective contraception during therapy and for at least 1 week after last dose
Patients who can lactate: Advised not to breastfeed during treatment and for at least 1 week after last dose

Obtained pretreatment complete blood count and hepatic panel
Hemoglobin < 10 g/dL threshold applies only after coexisting causes of anemia (iron, folate, or vitamin B12 deficiency; bleeding; hemolysis) are ruled out and treated
Antiviral prophylaxis for HBV must utilize agents with a high genetic barrier to resistance (entecavir or tenofovir)
Non-JAKI treatments include: androgens, danazol, prednisone, thalidomide, lenalidomide, erythropoietin stimulating agents

Treatment of intermediate or high-risk myelofibrosis (MF), including primary MF (PMF) or secondary MF (SMF; post polycythemia vera and post-essential thrombocythemia), in adults with anemia.
VHA use is restricted to alloHCT-ineligible adults with INT- or high-risk primary or secondary MF.

Anemia as primary treatment reason: MF-related anemia (Hg < 10 g/dL) with symptomatic splenomegaly or constitutional symptoms, where the primary reason for treatment is anemia.
Anemia without splenomegaly/constitutional symptoms: Myelofibrosis-related anemia (hemoglobin < 10 g/dL) with neither symptomatic splenomegaly nor constitutional symptoms, requiring a prior trial of one non-Janus kinase inhibitor (non-JAKI) treatment for myelofibrosis-related anemia.
Thrombocytopenia as primary treatment reason: Splenomegaly or symptoms where the primary reason for treatment is platelet count < 50 × 10^9/L, requiring a prior trial of pacritinib unless medically inadvisable.
Post-Ruxolitinib use (Platelets ≥ 50 × 10^9/L): Splenomegaly or symptoms with platelet count ≥ 50 × 10^9/L, requiring a prior trial of ruxolitinib unless medically inadvisable (e.g., due to pre-existing severe anemia [hemoglobin < 8 g/dL] or thrombocytopenia with platelets < 50 × 10^9/L).
Refractory Anemia: Persistent grade 3 anemia (hemoglobin < 8.0 g/dL) despite ruxolitinib dosage reductions.

Standard regimen: 200 mg PO once daily with or without food.
Severe hepatic impairment (Child-Pugh Class C): Reduce starting dose to 150 mg PO once daily.