Differences in Clinical and Molecular Characteristics and Outcome in Prefibrotic and Overt Primary Myelofibrosis According to 2016 WHO Criteria. a Study on 639 Patients of the Agimm Group

The revised 2016 World Health Organization (WHO) classification of myeloid neoplasms dictated distinct criteria for prefibrotic (prePMF) and overt primary myelofibrosis (PMF), based on bone marrow (BM) morphology, including fibrosis grade (G) AIM: to describe the characteristics and outcome of patients (pts) with a diagnosis of prePMF versus PMF according to the 2016 WHO criteria. METHODS. We used a database of ca 800 pts collected in 5 Italian tertiary centers of the AGIMM project. Pts annotated with diagnosis of pre/early PMF and PMF were identified, and BM biopsies were re-classified according to current criteria. A total of 639 pts with full information were retrieved; all were annotated for both driver mutations (JAK2V617F, MPLW515x, CALR) and High Molecular Risk mutations (HMR; Vannucchi et al, Leukemia 2013;1861), including ASXL1, EZH2, SRSF2, IDH1/2. RESULTS. Of the 639 pts, 274 (42.8%) were re-classified as prePMF and 365 (57.2%) as PMF. After a median follow-up (FU) of 3.6y, 212 pts (33.2%) had died, 23% prePMF vs 40.8% PMF (P65y old individuals (36.1% vs 46.8%, P= .004), had higher Hb (12.7 vs 10.7g/dL; P1% were found in 12.0% vs 26.3% (P25x109/L were similar. Abnormal karyotype in 18.5% prePMF vs 38.6% PMF (n=317; P10cm in 10.5% vs 24.1% (P The proportion of patients with JAK2V617F (and their median allele burden), MPLW515x and CALR (type I and type II) mutations was similar in prePMF and PMF; triple-negative (TN) pts were slightly more frequent in PMF (14%) than prePMF (9.9%; P=.041). Conversely, 24.8% of prePMF pts vs 41.1% PMF were HMR (P2 HMR mutations, that are prognostically negative (Guglielmelli et al, Leukemia 2014; 28), were found in 11.8% of PMF pts vs 4.7% prePMF (P Median survival (OS) was 17.6y in prePMF vs 7.2y in PMF (P2 HMR mutations (HR 9.3, 4.5-19.0 and 3.4,2.1-5.3, respectively; P CONCLUSIONS. This analysis of pts with contemporary diagnosis of prePMF and PMF disclosed important clinical, hematologic and molecular differences between the two, and indirectly suggested that they might represent a phenotypic continuum where increased grade of fibrosis associates with worsening of disease manifestations and outcome. Disclosures Vannucchi: Novartis: Consultancy, Research Funding, Speakers Bureau; Baxalta: Speakers Bureau; Shire: Speakers Bureau.