Outcomes of intensive and nonintensive blast-reduction strategies in accelerated and blast-phase MPN.

Transformation of BCR::ABL1 negative myeloproliferative neoplasms (MPN) to an accelerated or blast phase is associated with poor outcomes. The efficacy of AML-type intensive and nonintensive hypomethylating agent-based regimens is not well studied. We therefore performed a retrospective analysis of MPN-AP/BP patients (N=138) treated with intensive (N=81) and nonintensive (N=57) blast-reduction strategies. We used clinically relatable response criteria developed at the Princess Margaret Cancer Centre. The overall best response, comprising complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and reversion to chronic phase MPN (cMPN) in the intensive and nonintensive group was 77% (62/81) and 39% (21/54), respectively. Similar overall best response rates were observed in patients receiving induction with daunorubicin combined with cytarabine arabinoside (daunorubicin + ara-C) (74% [23/31]) or FLAG-IDA/NOVE-HiDAC (78% [39/50], p=0.78). However, patients receiving daunorubicin + ara-C more often required second inductions (29% [9/31] vs 4% [2/50], p=0.002). The majority of responses in the entire cohort were reversion to cMPN (55/83[66%]). CR and CRi comprised 30% (25/83) and 4% (3/83) of responses, respectively. Mutations in TP53 (OR 8.2 [95% CI 2.01, 37.1], p=0.004) and RAS pathway (OR 5.1 [95%CI 1.2, 23.7], p=0.03) were associated with inferior treatment response for intensively-treated patients, and poorer performance status (ECOG) was associated with inferior treatment response in both intensively- (OR 10.4 [95%CI 2.0, 78.5], p=0.009) and nonintensively-treated groups (OR 12 [95%CI 2.04, 230.3], p=0.02). In patients with paired samples prior to and after therapy (N=26), there was a significant residual mutation burden remaining irrespective of response to blast-reduction therapy.