Epidemiology, outcome, and risk factors for infectious complications in myelofibrosis patients receiving ruxolitinib: A multicenter study on 446 patients

Abstract

Infections represent one of the major concerns regarding the utilization of ruxolitinib (RUX) in patients with myelofibrosis. With the aim to investigate epidemiology, outcome and risk factors for infections in RUX-exposed patients, we collected clinical and laboratory data of 446 myelofibrosis patients treated with RUX between June 2011 and November 2016 in 23 European Hematology Centers. After a median RUX exposure of 23.5 months (range, 1-56), 123 patients (28%) experienced 161 infectious events (grades 3-4 32%, fatal 9%), for an incidence rate of 17 cases per 100 pts/y. The rate of infections tended to decrease over time: 14% of patients developed the first infection within 6 months, 5% between 6 and 12 months, 3.7% between 12 and 18 months, 3.4% between 18 and 24 months, and 7.9% thereafter (P < .0001). Respiratory tract infections were more frequently observed (81 events, 50%), and bacteria were the most frequent etiological agents (68.9%). However, also viral (14.9%) and fungal infections (2.5%) were observed. In multivariate analysis, previous infectious event (HR 2.54; 95% CI, 1.51-4.28; P = .0005) and high international prognostic score system category (IPSS) (HR 1.53; 95% CI, 1.07-2.20; P = .021) significantly correlated with higher infectious risk. On the contrary, spleen reduction ≥50% from baseline after 3 months of treatment (P = .02) was associated with better infection-free survival. Taken together, these findings reinforce the concept of disease severity as the most important risk factor for infections, and describe, for the first time, that a positive therapeutic effect in reducing splenomegaly may also reduce subsequent infectious complications.

Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease

“…In our cohort, 24% of the patients developed a bacterial infection, including bloodstream infections and pneumonia, with many patients having polymicrobial infections and 3 deaths related to these infections. High rates of bacterial infection have been observed by others in the setting of ruxolitinib use in cGVHD [17] and myelofibrosis [18], postulated to result from ruxolitinib interference with the innate immunity, especially neutrophil activation. Infectious complications were high in our cohort and included viral, bacterial, and fungal infections * For any reason other than resolution of cGVHD (eg, intolerance, cost).…”

Ruxolitinib for the treatment of inadequately controlled polycythemia vera without splenomegaly: 80-week follow-up from the RESPONSE-2 trial

“…The rates of overall and grade 3 or 4 infections were generally lower in patients treated with ruxolitinib compared to BAT, except an increased frequency of herpes zoster infections in the ruxolitinib arm. As reported in a recent publication by Polverelli et al (2017), these infections could be better controlled in real-world patients by employing active screening techniques, comprehensive patient education, and prophylactic or rapid access to treatment at symptom onset [21]. The incidence of NMSC was generally similar between ruxolitinib- and BAT-treated patients.…”

Life after ruxolitinib: Reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis

“…Nonetheless, long‐term studies have demonstrated a lack of response in some patients and loss of response in the majority of patients . Some patients may not tolerate ruxolitinib because of therapy‐related anemia, thrombocytopenia, or nonhematologic adverse events, in particular, infectious complications . Consequently, ruxolitinib is discontinued by most patients during the first 5 years of treatment.…”

“…9 Some patients may not tolerate ruxolitinib because of therapy-related anemia, thrombocytopenia, or nonhematologic adverse events, in particular, infectious complications. [10][11][12] Consequently, ruxolitinib is discontinued by most patients during the first 5 years of treatment. In the registration-enabling Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment (COMFORT)-I and COMFORT-II studies, which enrolled only intermediate-2-risk and high-risk patients, the rate of treatment discontinuation was approximately 50% at 3 years and 75% at 5 years; whereas the expanded-access JAK Inhibitor Ruxolitinib in Myelofibrosis Patients (JUMP) study, which also included intermediate-1-risk patients, reported a discontinuation rate of 35% after 3 years.…”