Ruxolitinib Therapy Is Associated With Significant Anemia, Red Blood Cell Transfusion Burdens

Patients with myelofibrosis (MF) and anemia receiving ruxolitinib (Jakafi; Incyte Corp) experienced significant anemia burden and shorter overall survival (OS), according to a retrospective cohort study using data from the Veterans Affairs Corporate Data Warehouse (VACDW). The findings, to be presented at 66th ASH Annual Meeting and Exposition, build on clinical understanding of real-world management of anemia in patients on ruxolitinib therapy.

Anemia depiction, red blood cells | Image Credit: © IttikornP - stock.adobe.com

MF is a fatal myeloproliferative neoplasm that causes extensive bone marrow scarring, leading to splenomegaly, thrombocytopenia, and anemia. Ruxolitinib is a janus kinase 1/2 (JAK) inhibitor that was approved by the FDA in 2011 for first line treatment of patients with intermediate and high-risk MF. Despite its capabilities in reducing symptoms and fibrosis, it is highly associated with increased risk of persistent or worsening anemia due to the adverse effect of myelosuppression.^1,2

In a retrospective cohort study, researchers evaluated rates of transfusion dependence (TD) and non-TD (NTD) at ruxolitinib initiation (defined as ≥1 or 0 unique dates with red blood cell transfusion [RBCT]), respectively, using electronic health records and claims data of 629 patients with MF and anemia (mean age 71.8; 96.3% male; 78.5% White) from the VACDW. Of the participants, 122 patients were TD (19.4%) and 507 were NTD (80.6%), with mean hemoglobin (Hb) levels of 8.0 g/dL (96.6% <10.5 g/dL) and 11.5 g/dL (41.4% <10.5 g/dL), respectively.²

The Kaplan-Meier method was used to analyze the end points of time to treatment discontinuation (TTD) and OS, and multivariable Cox proportional hazards models measured associations of TD status and Hb levels at ruxolitinib initiation with TTD and OS. The median follow-up was 15.7 months for TD patients and 26.8 months for NTD patients, with a median treatment duration of 8.9 months and 17.2 months, respectively.²

The most common starting dose was 5 mg two times a day (bid) for TD patients (24.6%) and 10 mg bid for NTD patients (25.9%), of which the dose at treatment discontinuation was 10 mg and 5 mg bid for both TD (n=85 [69.7%]; 10mg: 22.4%, 5mg: 21.2%) and NTD patients (n=331 [65.3%]; 10mg: 19.9%, 5mg: 22.1%), respectively.²

Upon initiation of ruxolitinib therapy, 122 patients (19.4%) were TD and 507 (80.6%) were NTD. According to the data, the median TTD in TD patients was 16.7 months (95% CI: 9.2–19.2) compared with 25.4 months (95% CI: 22.7–30.2) in NTD patients. At 24 months, 72% of TD patients and 85% of NTD patients were alive, and the median OS was not reached. The findings showed that TD patients had a higher risk for ruxolitinib discontinuation (HR 1.58; 95% CI: 1.20–2.09) and death (HR 2.03; 95% CI: 1.23–3.36).²

Of the participants, 92.6% of TD patients received anemia supportive care after ruxolitinib initiation, 38.5% received danazol, erythropoiesis-stimulating agents (ESAs), or immunomodulatory imide drugs (IMiDs), and 91.0% received RBCT. Comparatively, 43.6% received supportive care after ruxolitinib initiation, 18.5% received danazol, ESAs, or IMiDs, and 36.5% received RBCT, suggesting NTD patients achieve better treatment responses and are less likely to require anemia supportive care.²

The findings provide more data surrounding real-world outcomes for patients with MF and anemia on ruxolitinib therapy, highlighting the need for improved treatment strategies capable of safely and effectively managing anemia and RBCT burden.

REFERENCES

1. Patients with anemia and myelofibrosis have worse survival outcomes when treated with ruxolitinib. Pharmacy Times. December 2, 2024. Accessed December 4, 2024. https://www.pharmacytimes.com/view/real-world-analysis-shows-anemia-worsens-survival-in-myelofibrosis

2. Mascarenhas J, Perkins A, Shih Y, et al. 3807 burden and clinical outcomes in patients (pts) with myelofibrosis (mf) and anemia treated with ruxolitinib (rux): data from the veterans affairs corporate data warehouse (vacdw). Paper presented at: 66th ASH Annual Meeting and Exposition; December 8, 2024; San Diego, CA. Abstract 3807.