Outcome of patients with accelerated and blast‐phase myeloproliferative neoplasms not eligible for intensive chemotherapy or allogeneic hematopoietic cell transplantation treated by azacitidine alone or in combination—A FIM study

Abstract Accelerated‐phase (AP) or blast‐phase (BP) myeloproliferative neoplasms (MPNs) are associated with dismal prognosis, with non‐curative therapies such as hypomethylating agents (HMAs) considered in patients not eligible for intensive therapy, while some studies advocate for combination therapy with either ruxolitinib (RUXO) or venetoclax (VEN). To assess the relationship between treatment modalities and outcome, herein, we report a multicentric cohort of 149 patients (median age, 75 years) with AP/BP MPN not eligible for intensive therapy and/or allogeneic hematopoietic cell transplantation who received azacitidine (AZA) alone ( n = 60) or in combination ( n = 89; VEN [ n = 51], RUXO [ n = 27], or both [ n = 9], isocitrate dehydrogenase inhibitors [ n = 2]) between January 2019 and October 2023. With a median follow‐up of 15 months, the median overall survival of the full cohort was 8.04 months, with a 3‐year overall survival (OS) of 13%. Among disease characteristics, OS was lower in patients with BP (6.24 vs. 18.00 months in patients with AP disease, P = 0.03), complex karyotype (6.00 vs. 13.08 months, P = 0.005), and TP53 mutations (8.04 vs. 11.04 months, P = 0.009). OS was nonsignificantly higher in patients receiving AZA combinations (10.08 vs. 6.96 months in patients receiving AZA monotherapy, P = 0.12). When analyzing AZA combinations separately, patients who were treated with AZA–RUXO had higher OS (18.00 vs. 9.00 vs. 10.08 months in patients receiving AZA–VEN and AZA–VEN–RUXO, P = 0.015). The improved survival with AZA–RUXO in the absence of complex karyotype and/or TP53 mutations warrants further prospective validation. New therapeutic options are urgently needed, especially in patients with complex karyotype and/or TP53 mutations.