Is Cardiovascular-Related Mortality Risk in Primary Myelofibrosis Higher in the Post-Ruxolitinib Era?

The risk of cardiovascular-related mortality (CVM) in patients with primary myelofibrosis (PMF) has not increased following the approval of ruxolitinib over a decade ago, according to a study that will be presented at the 65th ASH Annual Meeting & Exposition, which is taking place December 9-12 in San Diego, California.

“Ruxolitinib, a Janus kinase inhibitor, was approved in 2011 for the treatment of primary myelofibrosis and has shown improved survival since its introduction. However, there are reports of possible cardiotoxicity linked to the medication,” the investigators wrote. “Given that patients with PMF may need therapy for several years, the cardiovascular safety profile of ruxolitinib has been the subject of increased scrutiny.”

In this retrospective analysis, Nosakhare Paul Ilerhunmwuwa and colleagues utilized data from the Surveillance, Epidemiology, and End Results Program Research Plus database, as well as the 17 Registries and Multiple Primary Standardized Incidence Ratio registry (2000-2020).

The researchers split the period into the pre-ruxolitinib (2003-2010) and post-approval ruxolitinib (2012-2019) eras and then compared the standard mortality ratios (SMRs) of CVD in both periods. The Kaplan-Meier method was used to estimate cumulative relative survival (CRS), and subdistribution hazard modeling was used to predict CVM overall. In total, the researchers analyzed 4509 patients with PMF.

According to the findings, there was no significant difference in the proportion of deaths due to cardiovascular disease between the pre- and post-ruxolitinib eras. The investigators observed that compared with the general population, patients with PMF had a higher overall CVM independent of the era of diagnosis. Moreover, they noted that in terms of specific CVD, the SMRs of diseases of the heart, hypertension without heart disease, and cerebrovascular disease were higher in the pre-ruxolitinib period compared with the post-ruxolitinib era. Also, no significant difference was found in mortality risk from other CVD compared with the general population in either era.

“The risk of CVM in PMF compared [with] the general population did not seem to have increased in the era following the approval of ruxolitinib. The SMRs for overall and some specific cardiovascular diseases appear to be lower in the ruxolitinib era compared [with] the period before its approval,” the researchers concluded.

Reference

Ilerhunmwuwa N, Rayapureddy AK, Uche IN, Wasifuddin M, Wang J-C. Cardiovascular-related Mortality risk in primary myelofibrosis in pre-ruxolitinib and ruxolitinib eras. Abstract #552. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.