Myelofibrosis ASH education 2022

 

Difference between proliferative MF and cytopenic MF

Proliferative MF: higher WBC, Hb and plt. Typically less blasts, less fibrosis, and lower risk score.

More likely to be associated with post PV or ET. 

Bigger spleen+, higher JAK2 VAF

More treatment options, better outcomes

1.  Ruxolitinib and fedratinib, can both improve constitutional symptoms and splenomegaly but carry on-target risks of worsening anemia and thrombocytopenia, limiting their use in patients with cytopenic MF.

2. Pacritinib, selective Jak2 inhibitor, was approved in 2022 to treat patients with symptomatic MF and a platelet count lower than 50 × 10⁹/L

Steps in the initial assessment of patient with MF:

a. Risk stratification: MIPSS 70 and or GIPSS, DIPSS plus etc

b. Assess symptom burden with MPN-10

c. Clinical exam: constitutional symptoms, splenomegaly

d. Decide if cytopenic type or proliferative type

Lower risk MF ( DIPSS < 2, DIPSS plus 0 or 1, MIPSS 70 3 or less)

1. Asymptomatic: observe

2.  Symptomatic: anemia--> measure epo level. If epo < 500, use ESA +/- danazol, luspatercept

3. Symptomatic: constitutional and splenomegaly: Ruxulotinib, fedratinib, pacritinib. Low dose Jakafi if plt count 50-100 k, if plt < 50K use pacritinib ( approval based on spleen size)

Higher risk: (DIPSS 2 or higher) if transplant candidate--> allow HCT if bridging Jakafi

If not a transplant candidate, treat as for symptomatic low risk.

Degree of anemia and tpenia correlate with worse OS and risk of AML transformation ( if plt < 50K).

Plt < 50K--> more fibrosis and higher blast count.

Cytopenic is more common in primary MF.

Jakafi:

Starting dose based on platelet count and escalate as able.
Early anemia is common, with gradual improvement (so dose adjustments not indicated for early anemia

Fedratinib: can use after Jakafi failure and still gets spleen vol reduction. GI se common. Wernicke's. 400 mg daily. Black  box --> thiamine monitoring.

No starting dose reductions needed for moderate thrombocytopenia, but dose reduce for worsening platelets.
Early nausea or diarrhea are common.
Monitor thiamine and for signs of encephalopathy.
Monitor renal function and liver function.

Pacritinib: 200 mg BID. cardiac toxicity in earlier trials. Monitor Qtc and EF.

Less myelosuppression.
Early nausea/diarrhea are common and generally improve with supportive care.
Caution in those with CV disease or recent hemorrhage.
Monitor QTc.
Monitor for bleeding

Momelotinib

Rare risk of neuropathy