Real-world risk of vascular events in patients with myeloproliferative neoplasms compared to the danish general population Free

Introduction: Treatment in myeloproliferative neoplasms (MPN) aims to lower the risk of thrombotic events, alleviate MPN-related symptoms and prevent disease progression. In Denmark, all patients with MPN are followed at public hospitals that are obligated to report individual-level data to the Danish Chronic Myeloid Neoplasm Register (DCMR). We report contemporary five-year nationwide rates of vascular events (VE) - arterial thrombotic (VE_A), venous thrombotic (VE_V) and hemorrhagic (VE_H), respectively.

Methods: We included MPN patients diagnosed from 2010 to 2022 from the DCMR. The MPN cohort was matched 1:10 to non-MPN persons (general population; GP) on age, sex, region and Charlson comorbidity index (CCI). We report rate ratios (RR) as rate_MPN/rate_GP (VE_A, VE_V and VE_H, in this order), adjusted for age, sex, CCI and MPN subtype and crude VE rates as events/10⁴ person years along with 95 percent confidence intervals. We stratified for the following MPN characteristics: MPN subtype at baseline (ET, PV, PMF, preMF, MPN-U), splenomegaly by palpation or imaging (yes, no), and driver mutation (JAK2V617F, CALR). The rates in patient subgroups and the RR between subgroups and matched comparators were obtained using multivariable Poisson regression models.

A VE was defined as a new hospital contact pertaining to a VE type in a specific organ system in a 90-day period through grouping of relevant ICD-10 codes obtained from national health registries. The rate of VE was then defined as the number of such events in a period from 90 days after diagnosis until five years after, or death, migration or end-of-study (December 2024), whichever came first.

Results: A total of 6,397 MPN patients (n_ET=2150, n_PV=2150, n_PMF=904, n_preMF=95, n_MPN-U=1098) and 63,022 unique controls were included. The median age at MPN diagnosis was 70 years. 27 percent had splenomegaly. 76 percent of the MPN cases were JAK2 V617F mutated and 6 percent were CALR mutated. The median follow-up time was 6.0 years for MPN patients and 6.7 years for controls.

RR of VE_A, VE_V and VE_Hfor MPN compared to GP were for ET: 1.50 (1.23-1.83), 2.22 (1.56-3.14), 1.99 (1.57-2.53); PV: 1.47 (1.22-1.77), 2.96 (2.23-3.92), 1.59 (1.27-2.01); PMF: 1.46 (1.13-1.87), 2.97 (1.85-4.77), 4.41 (3.40-5.71); preMF 1.17 (0.56-2.49), 6.91 (1.77-27.07), 3.32 (1.40-7.84) and MPN-U: 1.51 (1.20-1.91), 3.13 (2.12-4.63), 3.34 (2.52-4.42). These results point toward to a stepwise increase in RR of VE_V from ET/PV through PMF to preMF/MPN-U. For VE_H, RR is lowest for ET/PV followed by preMF/MPN-U and highest for PMF. The RR difference between MPN subtypes showed a statistically significant difference between subtypes for VE_H, while for VE_A and VE_V these differences were not significant. For patients with splenomegaly, RR were 1.47 (1.15-1.88), 4.00 (2.74-5.83), 3.41 (2.60-4.47) and for patients without splenomegaly RR were 1.48 (1.26-1.74), 1.79 (1.37-2.35), 2.06 (1.70-2.49). These results indicate that patients with splenomegaly harbor risks of VE_V and VE_H that are around four times higher than their non-MPN controls, while patients without splenomegaly have double the risk of their non-MPN controls. JAK2V617Fmutated patients exhibited VE rates of 335 (265-423), 291 (243-347), 175 (153-200) and RR of 1.42 (1.26-1.60), 3.00 (2.47-3.66), 2.23 (1.92-2.58), while CALR mutated patients had VE rates of 217 (140-337), 321 (172-599), 129 (77-214) and RR of 1.18 (0.73-1.89), 3.23 (1.56-6.69), 1.96 (1.04-3.69).

Thus, all rates and RR were significantly elevated except for RR of VE_A for preMF patients and RR of VE_A and rate of VE_H for CALR mutated patients.

Conclusion: The risk of all types of VE with current treatment is still elevated for MPN patients compared to the general population, except for CALR mutated - and preMF patients, for which there was no evidence of elevated VE_A. Across clinical phenotypes, the risk of VE_Ais balanced, while VE_V and VE_H risks are higher for more advanced disease, i.e. for PMF and patients with splenomegaly. Interestingly, rate ratios of JAK2V617F and CALR mutated patientswere evenly increased relative to their respective controls for all types of VE. The higher VE_V and VE_H rates for more advanced disease may indicate a need for disease-modifying treatment to further improve the prognoses of these patients. Additional analyses incorporating cardiovascular risk factors, allelic burdens, organ-specific and absolute risk estimates analyses will be presented at ASH.