Oral Decitabine/Cedazuridine Is an Effective Ambulatory Therapy for Patients With Myelofibrosis Refractory to JAK2 Inhibitor Therapy.

Background: Outcomes are dismal for patients with myelofibrosis (MF) who are no longer responsive to JAK2 inhibitors (JAKi) and/or have increasing blast cell numbers. Although prior reports have suggested the benefits of intravenous decitabine (DAC) combined with ruxolitinib for patients with Myeloproliferative Neoplasm (MPN) accelerated/blast phase (AP/BP), decitabine-cedazuridine (DEC-C), an oral fixed-dose combination providing equivalent pharmacokinetic exposure, has not been evaluated in MF.
Methods: We conducted a retrospective analysis of 14 patients with high-risk MF refractory to ruxolitinib or MPN-AP (10-19% blasts) treated with DEC-C +/- JAKi at Mount Sinai Hospital from 2021 to 2024.
Results: The cohort was elderly (median age,76 years) and almost uniformly possessed high risk mutations with 13 of the 14 patients progressing on JAKi therapy. With a median follow-up of 9.4 months, the median overall survival (OS) was 29 months for the entire cohort. Median OS was 10.8 months for MPN-AP and was not reached for ruxolitinib refractory MF patients. All patients (n = 9) receiving > 4 cycles of DEC-C had clinical benefit exemplified by a reduction in blast cell numbers, spleen size, and lack of progression to MPN-BP (78%). Furthermore, 3/14 patients proceeded to allogeneic stem cell transplant. Myelosuppression was a common adverse event which was managed by reducing the number of days of administration of DEC-C from 5 to 3 per cycle.
Conclusions: This report demonstrates the feasibility, tolerability, and clinical benefit of an exclusively ambulatory regimen for high-risk, elderly patients with advanced MF which warrants further evaluation in a prospective clinical trial.
Competing Interests: Disclosures D.T. receives contracted research funding paid to his institution from Sobi, Astellas Pharma, Gilead and Cogent Biosciences and consulting fees from Novartis, AbbVie, Sierra Oncology, GSK and Cogent Biosciences. J.M. receives research funding paid to his institution from Incyte, Novartis, BMS, CTI/Sobi, Abbvie, Geron, Kartos and PharmaEssentia. Consulting fees paid to me by Incyte, Novartis, CTI/Sobi, Abbvie, Karyopharm, Kartos, Geron, GSK, Sumitomo, BMS, MorphoSys, Galecto, Pfizer, Merck, Roche and PharmaEssentia. R.H. received research grant funding through his institution from the following sources: Citi BioPharma Corp, Curis, Inc., Dexcel Pharma Technologies Ltd. Genentech, Kartos Therapeutics, Karyopharm Therapeutics, Inc., Kymera Therapeutics, OncoMyx Therapeutics, Novartis, Protagonist Therapeutics, Repare Therapeutics, Translational Drug Development (TD2), Turning Point Therapeutics, and the NIH/NCI. Additionally, he has received funding as an advisor/consultant from the following sources: AbbVie, Ionis Pharmaceuticals, Protagonist Therapeutics, Silence Therapeutics, GlycoMimetics, Dexcel Pharma Technologies LTD, Sumitomo Pharma Oncology, and Cellenkos, Inc. Finally, he holds a share of a patent filed by Dompé farmaceutici S.p.A. Y.Z.G. received research grant funding through her institution from the following sources: Protagonist Therapeutics, Repare Therapeutics, and the NIH/NIDDK. YZG has received funding as an advisor/consultant from the following sources: Bay Clinical, Takeda, Denali, Ionis Pharmaceuticals, Protagonist Therapeutics. No other relevant financial disclosures for other authors.
(Copyright © 2024. Published by Elsevier Inc.)