The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes

Abstract

There is a paucity of data regarding the impact of mutations on outcomes in accelerated-phase (AP) and blast-phase (BP) myeloproliferative neoplasms (MPNs). Moreover, it is unknown whether mutational status affects survival, as seen in chronic-phase MPNs. Therefore, we performed a retrospective analysis of all patients treated at our institution with AP/BP MPNs (N = 122; AP = 14; BP = 108) to comprehensively describe the mutational profile and correlate with clinical outcomes. Targeted sequencing with a 54-gene panel was performed. Forty-four patients were treated with intensive therapy, 27 with nonintensive therapy, and 51 with best supportive care (BSC). The most common mutation was <i>JAK2V617F</i>, occurring in 55% of subjects; <i>CALR</i> was found in 13% of patients and <i>MPL</i> in 6%. Thirty-two (26%) patients were triple negative. Other frequently mutated genes were <i>ASXL1</i> (30%), <i>TET2</i> (25%), <i>SRSF2</i> (22%), <i>RUNX1</i> (20%), and <i>TP53</i> (17%). Mutations in 1, 2, 3, and ≥4 genes were seen in 15%, 13%, 25%, and 46% of patients, respectively. There was no difference in survival between patients treated with intensive vs nonintensive therapy, and the benefit of intensive therapy was limited to patients who were able to undergo transplantation. <i>TP53</i> was the only individual mutation to correlate with shorter overall survival (hazard ratio, 1.89; <i>P</i> = .03). In the multivariate analysis, mutated <i>TP53</i>, ≥4 mutations, low albumin, increased peripheral blood blasts, ≥3 cytogenetic abnormalities, and BSC were associated with shorter survival. In conclusion, mutational data enhance the understanding of patients with AP/BP MPN who are likely to benefit from current therapeutic options.