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$Emeka Patrick Chukwuka: Treatment Sequencing After JAK Inhibitor Failure in Relapsed and Refractory Myelofibrosis$

Emeka Patrick Chukwuka/LinkedIn

Aug 8, 2026, 13:33

Emeka Patrick Chukwuka: Treatment Sequencing After JAK Inhibitor Failure in Relapsed and Refractory Myelofibrosis

Emeka Patrick Chukwuka, Hematologist and Clinical Pathologist, shared a post on LinkedIn:

“Clinical Haematology Series

Two JAK inhibitors. Both failed. A 50-year-old teacher with a spleen 16cm below her costal margin. What comes next?

This is Sandra. And her case is a masterclass in why relapsed/refractory myelofibrosis demands a structured, sequential decision framework — not improvisation.

The backstory matters.

Ten years of polycythaemia vera, transformed to post-PV myelofibrosis. Massive splenomegaly. Severe pruritus, drenching night sweats, 6kg weight loss. And underneath it all — HFrEF with an ejection fraction of 35–40%, NYHA Class II. Well-compensated, but watching.

Ruxolitinib at 3 months: a partial story with a clear endpoint.

Pruritus resolved — that’s the win. But the spleen reduced only 37.5%, falling short of the 50% target that defines meaningful response. Hgb dropped to 7.8 g/dL. Transfusion-dependent despite ESA support. By any standard definition, this is ruxolitinib failure.

The switch to fedratinib — and the step most clinicians miss:

Checking thiamine levels before starting fedratinib is an absolutely essential step to prevent Wernicke encephalopathy.

Start fedratinib, tapering ruxolitinib over two weeks; overlapping them prevents cytokine rebound and symptom flares.

Abrupt ruxolitinib discontinuation syndrome is a clinical emergency. The taper is the safety net.

When fedratinib also fails — the third-line framework:

Re-treating with ruxolitinib: already failed at full dose; lower doses mean worse control and don’t address anaemia
Momelotinib — ACVR1 (Activin A receptor type 1, also known as ALK2) mechanism targets anaemia and spleen
Pacritinib trial — purpose-built for severe thrombocytopenia
Pelabresib trial — BET (Bromodomain and Extra-Terminal motif) inhibitor combination strategy
Reassess allogeneic transplant candidacy — always on the table

Sandra’s 24-week outcome on pelabresib and ruxolitinib clinical trial:

Spleen: 13cm to 6cm
Hgb stable at 9.8 g/dL
Transfusion-free for 12 weeks
Back to full-time teaching

The lesson: in relapsed/refractory MF, the sequence of decisions — and the transitions between them — are as therapeutically important as the drugs themselves.

Know your switching protocol. Check the thiamine. Reassess transplant at every failure point.”

$Emeka Patrick Chukwuka: Treatment Sequencing After JAK Inhibitor Failure in Relapsed and Refractory Myelofibrosis$