Oral Decitabine/Cedazuridine Is a Tolerable and Effective Ambulatory Regimen for Patients with Advanced Myeloproliferative Neoplasms

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.1828-1828
• Main Authors: Sivakumar, Ganesh, Handa, Shivani, Srisuwananukorn, Andrew, Tremblay, Douglas, Mascarenhas, John, Kremyanskaya, Marina, Ginzburg, Yelena, Wang, Xiaoli, Hoffman, Ronald
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-178822

Background: Treatment options are limited for patients (pts) with advanced myeloproliferative neoplasms (MPNs). Most pts become refractory to JAK2 inhibitor (JAKi) therapy by 3 years with subsequent survival of only 11-16 months. Sequential treatment with chromatin-modifying agents including decitabine (D) can upregulate CXCR4 expression, correct abnormal trafficking of myelofibrosis (MF) stem cells, and eliminate JAK2V617F+ MF stem and progenitor cells in preclinical models ( Wang et al, Cancer Res 2019, Blood 2010). Combination therapy with intravenous D and ruxolitinib (Rux) had a favorable effect on overall survival (OS) in a phase 2 study of MPN-accelerated/blast phase pts ( Mascarenhas et al, Blood Adv 2020) and prolonged survival in a cohort of DIPSS-plus high-risk MF pts ( Bader et al, Leuk Res 2015). Oral decitabine/cedazuridine (DC), therefore, represents an attractive ambulatory treatment option for pts with advanced MPNs. Methods: We retrospectively reviewed the electronic health records of pts with advanced high-risk MF (AHR-MF) or MPN- accelerated phase (MPN-AP) seen at our institution that were treated with DC with or without a JAKi from 1/2021-7/2023. MPN-AP was defined by the presence of 10-19% blasts in peripheral blood/ bone marrow. AHR-MF was defined by the presence of 4-9% circulating blasts or 5-9% blasts in the bone marrow, and/or refractoriness to a JAKi. Results: A total of 14 pts, 7 each with MPN-AP and AHR-MF, respectively received DC therapy (Table 1). Most pts (8/14 or 57%) were older than 75 years. All pts were classified as high risk/very high-risk (MIPPS70 plus v.2). Ten (71%) pts had one or more high molecular risk mutations ( ASXL1, EZH2, SRSF2, IDH1/2, U2AF1), with the most prevalent being ASXL1 mutations in 8/14 (57%) pts. Other somatic mutations included NF1, KRAS, NRAS, BRAF, GATA2, STAG2, DNMT3A and TET2 genes. Eight of the 14 pts (57%) had either an unfavorable or very high-risk karyotype (MIPSS70 plus v.2). Thirteen pts had previously failed JAKi therapy. The median number of cycles of DC therapy was 2 (range,1-6) and 4 (range,1-26) for MPN-AP and AHR-MF pts, respectively and 4/7 pts received a concurrent JAKi in each group. Two pts in AHR-MF cohort were successfully bridged to transplant. Two pts in the MPN-AP group discontinued treatment after cycle 1 due to neutropenic sepsis and progression to blast phase, respectively. Among MPN-AP pts who received ≥ 2 cycles of DC, circulating blasts were reduced to ≤ 5% in 4/