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

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2024-09, Vol.24 (9), p.e314-e319
• Main Authors: Handa, Shivani, Sivakumar, Ganesh, Srisuwananukorn, Andrew, Dueck, Amylou, Tremblay, Douglas, Mascarenhas, John O, Ginzburg, Yelena, Kremyanskaya, Marina, Hoffman, Ronald
• Format: Article
• Language: English
• Subjects: Chromatin-modifying agent; Hypomethylating agent; MPN-accelerated phase; myeloproliferative neoplasms; Ruxolitinib-refractory
• ISSN: 2152-2650; 2152-2669; 2152-2669
• DOI: 10.1016/j.clml.2024.05.012

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. 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. 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. 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. Patients with myelofibrosis (MF) who are refractory to JAK2 inhibitors (JAKi) and/or have increasing blast cell numbers have dismal prognosis. We studied a novel ambulatory regimen of decitabine-cedazuridine (DEC-C) +/- JAKi therapy in patients with high-risk MF who were refractory to prior JAKi or MPN-accelerated phase. We demonstrate the therapeutic benefit of this strategy as evidenced by reduction or stabilization of blast cell counts, decrease in splenomegaly or successful bridge to stem-cell transplant. Myelosuppression is a common adverse event but treatment length reduction from 5 to 3 days of DEC-C/cycle is feasible and reduces toxicity without comprising the efficacy.