Dose escalation upfront may reduce the need for dose reduction during ruxolitinib therapy for myelofibrosis, according to a study in the Journal of Hematology & Oncology.

Ruxolitinib, a Janus-associated kinase 1 /2 (JAK) inhibitor, reduces spleen volume and improves symptoms in patients with the myeloproliferative neoplasms, myelofibrosis and polycythemia vera. About half of myelofibrosis patients treated with ruxolitinib develop grade 3 or 4 anemia or thrombocytopenia, however, leading to dose reductions or transfusions.

Doctor discussing dosing with patient. Source: Getty

Researchers led by Moshe Talpaz, MD, a professor at the University of Michigan Health System in Ann Arbor, enrolled 45 patients with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombosis myelofibrosis in the phase 2 study. Almost 70% of patients had a Dynamic International Prognostic Scoring System (DIPPS) score of 1 or 2, indicating intermediate-1 risk disease.

All patients started with ruxolitinib 10 mg twice daily. If that dose did not prove efficacious, then it increased to 15 mg twice daily at 12 weeks and, if needed, to a maximum dose of 20 mg twice daily at 18 weeks.

Three patients did not complete the 24-week treatment period; two withdrew consent and one progressed to myelodysplastic syndrome and later died. Five were lost to follow up prior to its end.

Median reduction in spleen volume was 17.3%, with 26 patients achieving more than 10% reduction. Symptom severity, as measured by the Myelofibrosis Symptom Assessment Form Total Symptom Score (MFSAF TSS) declined a median of 45.6% from initiation to week 24. Both spleen volume reduction and symptom improvement demonstrated clear dose response.

While 93.3% of patients experienced a treatment-emergent adverse event, only arthralgia, fatigue and anemia affected more than 20% of participants and none of those affected more than 27%.  Grade 3 or 4 anemia occurred in 20% (9) of patients. Only one patient developed thrombocytopenia. Dose reductions related to anemia occurred in 11.1%, while dose reductions resulting from thrombocytopenia occurred in 6.7% of patients. Two patients had serious adverse events, with one patient each having cholelithiasis and dehydration, and one patient died following development of myelodysplastic syndrome.

The authors suggested that diverging from the NCCN guidelines for myeloproliferative neoplasms, which recommend adhering to ruxolitinib dosing per the product label, could be warranted in some cases.

They wrote: “Results from this open-label, multicenter, single-arm, phase 2 study suggest that initiating therapy at lower doses can be performed safely and may provide clinical benefit, including improvements in splenomegaly and symptoms, in patients with MF for whom anemia is, or is likely to become, a concern while receiving treatment with ruxolitinib.”