Treatment landscape and outcome of myeloproliferative neoplasms in asia: Interim analysis of the Asian myeloproliferative neoplasm registry

Abstract Background Large multicenter analysis of myeloproliferative neoplasms (MPNs) has not been conducted in Asia. Aims This project aims to define the clinicopathologic characteristics, treatment landscape and outcome of MPNs in Asia. Methods This is a multicenter retrospective and prospective cohort analysis. Survivals were analyzed with the Kaplan-Meir method and differences in survivals were analyzed with the log-rank test and multivariate cox-proportional hazard model. Propensity score matching (PSM) was used to evaluate impacts of specific therapies on survivals. Results The cohort comprised 969 patients. The diagnoses, patients, median (range) age at diagnosis and duration of follow-up were respectively polycythemia vera (PV): 106 men, 102 women, 54.9 (12.9-92) years, 8.4 (0.1-38.5) years; essential thrombocythemia (ET): 171 men, 233 women, 54.2 (13-97.6) years, 8.6 (0.3-44.9) years; pre-fibrotic primary myelofibrosis (pre-PMF):59 men, 57 women, 61 (14-96.6) years, 4.3 (0.1-24.6) years; and MPN-unclassifiable (MPN-U): 44 men, 36 women, 69.9 (26.6-94.8) years, 60.1 (31.6-96) years. One hundred and forty patients (PV, N=62; ET, N=76, MPN-U, N=2) progressed to secondary myelofibrosis (SMF) after a median of 15.1 years (95% confidence interval, CI: 14.2-16.4). Treatment included hydroxyurea (PV: N=179, 86.1%; ET:N=341,84.4%; pre-PMF: N=117, 72.9%; fibrotic PMF: N=59, 50.9%; MPN-U: N=65,81.2%);pegylated-interferon alfa, PEG-IFNa (PV:N=86, 41.3%; ET: N=161, 39.9%; pre-PMF: N=85, 52.8%; fibrotic MF: N=22, 19%; MPN-U: N=13, 16.2%); ruxolitinib (fibrotic PMF: N=84, 72.4%; SMF: N=91, 65%). Forty patients (fibrotic PMF, N=19; SMF, N=21) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Seventy-one patients (7.3%) (PV, N=22; ET, N=28, pre-PMF, N=7; fibrotic PMF, N=11; MPN-U, N=3) progressed to acute myeloid leukemia after a median of 19.4 years (95% CI: 16.8-20.8). The median overall survival (OS) (95% CI) of patients with PV, ET, pre-PMF, fibrotic PMF and MPN-U was 24.8 (20.1-29.5), 22.3 (19.1-25.5), 14.7 (9-20.3), 10.3 (7.5-13.2) and 8.9 (5.4-12.3) years respectively. Patients who received PEG-IFNα at any time during the course of the disease were compared with those who never received PEG-IFNα. The use of PEG-IFNα was associated with superior OS in PV (P=0.004), ET (P < 0.001), and pre-PMF (P < 0.001) but not in fibrotic PMF (P=0.18) and MPN-U (P=0.08). The use of PEG-IFNα was associated with superior AML-free survival in PV (P=0.02), ET (P<0.001) and pre-PMF (P<0.001) but not in fibrotic PMF (P=0.52) and MPN-U (P=0.08). The use of PEG-IFNα was associated with superior SMF-free survival in ET (P < 0.001) but not in PV (P=0.15) and MPN-U (P=0.08). On PSM analysis, the use of PEG-IFNα was associated with superior OS (P<0.001) in MPN. In patients with fibrotic PMF and SMF, there was no statistically significant difference in OS (P=0.59) and AML-free survival (P=0.83) between patients who received ruxolitinib alone without allo-HSCT versus those who received allo-HSCT. Conclusions In patients with PV, ET and pre-PMF, the use of PEG-IFNa improved survivals in Asia. The use of ruxolitinib in fibrotic PMF and SMF was associated with survivals similar to those undergoing allo-HSCT. Further analysis is ongoing to evaluate prognostic indicators in different diseases and treatment subgroups. ClinicalTrials.gov Identifier: NCT05882773 Acknowledgment: This study was partly supported by a research grant from Novartis.