For patients with polycythemia vera (PV), there are no differences in recommendations for preventing complications when using ruxolitinib than for myelofibrosis (MF).
With the exception of infections with the varicella zoster virus (VZV), the risk of infection with ruxolitinib treatment is lower for patients with polycythemia vera (PV) than for patients with myelofibrosis (MF), according to a new literature review assessing the risk in these patients.
However, despite the lower risk among patients with PV, there are no fundamental differences in recommendations for preventing complications for ruxolitinib-treated patients with PV than for patients with MF. In fact, the researchers note that there are no specific recommendations in the literature for preventing ruxolitnib-associated infections in patients with PV.
“Whether this will also be the case in the future can only be answered based on long-term data from many PV patients treated with RUX,” wrote the researchers. “Long-term studies and corresponding registers on this topic are therefore essential.”
According to the researchers, the majority of currently available data on the risk of infections associated with ruxolitinib across MPNs is available for MF, as these patients have higher infection rates.
Data from studies of patients with MF treated with ruxolitinib
In the COMFORT-I trial, the most common infections that occurred during randomized treatment with ruxolitinib after 3 years of follow-up included urinary tract infections (10.5% in 0 to <12 months, 6.7% in 12 to <24 months, 7.7% in 24 to <36 months, and 6.0% after ≥36 months) and zoster infections (2.1% in 0 to <12 months, 3.5% in 12 to <24 months, 3.4% in 24 to <36 months, and 0% after ≥36 months). The researchers noted that long-term treatment with ruxolitinib was not associated with an increased incidence of infections.
In the JUMP trial—the largest MF trial to date—infections that occurred in at least 1% of the 1144 ruxolitinib-treated patients included nasopharyngitis (6.3%), urinary tract infection (6.0%), pneumonia (5.3%), bronchitis (4.2%), herpes zoster (3.6%), influenza (3.0%), upper respiratory tract infection (2.9%), cystitis (2.5%), gastroenteritis (1.8%), respiratory tract infection (1.8%), and oral herpes (1.6%).
Data from studies of patients with PV treated with ruxolitinib
“Although the risk of ruxolitinib-associated infections is lower with polycythemia vera compared to myelofibrosis, there is an increased risk of infection,” wrote the researchers. “The most important infections that occur during ruxolitinib treatment are particularly herpes zoster infection, but bacterial (urinary tract infections, pneumonia, and sepsis) and other viral infections (such as influenza and hepatitis B reactivation) also occur.”
Follow-up data from both the RESPONSE and RESPONSE-2 trials showed that with the exception of herpes zoster infections, which is caused by VZV, rates of all grade infections were lower among patients receiving ruxoitinib than among patients receiving best available therapy (BAT).
In 5-year follow-up data from the RESPONSE trial, infection rates per 100 patient-years of exposure were 18.9 in patients originally randomized to ruxolitinib, 19.1 in patients receiving ruxolitinib after crossover, and 59.8 in patients receiving BAT. In 3-year follow-up data from the RESPONSE-2 trial, rates of all grade and grade 3-4 were 24.9 and 2.3 in the ruxolitinib-treated cohort compared with 33.7 and 3.7 among patients in the BAT cohort. Rates of all-grade herpes zoster infection were 3.8 in the ruxolitinib cohort, 7.5 in the crossover cohort, and 0 in the BAT cohort.
Sadjadian P, Wille K, Griesshammer M. Ruxolitinib-associated infections in polycythemia vera: review of the literature, clinical significance, and recommendations. Cancers. 2020;12(11):3132. doi: 10.3390/cancers12113132