Patients With Anemia and Myelofibrosis Have Worse Survival Outcomes When Treated With Ruxolitinib

Patients with myelofibrosis (MF) and anemia have poorer survival outcomes compared with nonanemic patients when treated with ruxolitinib (Jakafi; Incyte Corp), according to a retrospective analysis of adult patients in the US Flatiron Health electronic health record–derived de-identified database. The findings, to be presented at the 66th American Society of Hematology Annual Meeting and Exposition in San Diego, California, provide real-world evidence that new or worsening anemia during treatment with ruxolitinib is associated with an increased risk of death, highlighting the need for therapeutic options that address anemia without compromising survival.¹

Blood cells, anemia illustration | Image Credit: © Natalia - stock.adobe.com

MF is a myeloproliferative neoplasm that results in the overproduction of hematopoietic stem cells, resulting in increasingly reduced red blood cell production and bone marrow fibrosis. Scarring of the bone marrow leads to severe anemia, which affects approximately 35% to 54% of patients at diagnosis of primary MF. Anemia plays a key role in negatively impacting overall survival and can result from treatment with ruxolitinib, a Janus kinase inhibitor therapy.^1-3

Ruxolitinib was approved by the FDA in 2011 for treatment of intermediate and high-risk MF based on the results from both the COMFORT–1 (NCT00952289) and COMFORT–2 (NCT00934544) trials. In 2019, ruxolitinib became the first approved therapy for steroid-refractory acute graft-versus-host disease for patients 12 and older. Studies have shown ruxolitinib improves splenomegaly and other MF symptoms. Additionally, findings published in Nature suggest that ruxolitinib may help address the underlying fibrotic changes that often lead to severe complications. However, anemia is a common, serious adverse effect of treatment with ruxolitinib.^4-6

In the analysis, the researchers aimed to determine the association between anemia status at treatment initiation, whether new or worsening anemia, and overall survival (OS) in patients with MF. Their analysis included 286 patients with an MF diagnosis and ruxolitinib treatment between January 1, 2013, and March 1, 2023, with a mean age of 72 years and a mean hemoglobin level of 10.3 g/dL. They were divided into subgroups depending on anemic status, of which 147 patients were anemic and 139 were nonanemic at baseline.⁷

According to the data, OS was significantly shorter in baseline anemic patients with no worsening anemia (HR, 1.87; 95% CI, 1.13-3.08; P<.05), baseline nonanemic patients with new or worsening anemia (HR, 2.04; 95% CI, 1.21-3.45; P<.01), and baseline anemic patients with worsening anemia (HR, 2.53; 95% CI, 1.53-4.19; P<.001), compared with nonanemic patients.⁷

Across all participants, new or worsening anemia on treatment was significantly associated with shorter OS regardless of baseline anemia status (HR, 1.68; 95% CI, 1.18-2.40; P<.01), and was most profound in patients without anemia at baseline (HR vs patients without new or worsening anemia on treatment, 2.17; 95% CI, 1.27-3.70; P<.01). Additionally, worsening anemia on treatment was also numerically associated with shorter OS (HR vs patients without new or worsening anemia on treatment, 1.30; 95% CI, 0.81-2.08; P=.28).⁷

The real-world analysis supports data that patients with MF and anemia treated with ruxolitinib have poorer OS outcomes, calling for new approaches to this agent and its use in the MF treatment landscape. Continued studies are needed to identify combination therapies and methods of overcoming anemia during ruxolitinib therapy.

REFERENCES

1. Study finds ruxolitinib may slow fibrosis progression in myelofibrosis. Pharmacy Times. September 24, 2024. Accessed November 27, 2024. https://www.pharmacytimes.com/view/study-finds-ruxolitinib-may-slow-fibrosis-progression-in-myelofibrosis

2. Myelofibrosis. Mayo Clinic. December 28, 2022. Accessed November 27, 2024. https://www.mayoclinic.org/diseases-conditions/myelofibrosis/symptoms-causes/syc-20355057

3. Gupta V, Harrison C, Hexner E, et al. The impact of anemia on overall survival in patients with myelofibrosis treated with ruxolitinib in the comfort studies. Haematol. November 12, 2016. doi:10.3324/haematol.2016.151449

4. Haq M, Adnan G. Ruxolitinib. StatePearls [Internet]. June 5, 2023. https://www.ncbi.nlm.nih.gov/books/NBK570600/

5. Controlled myelofibrosis study with oral jak inhibitor treatment: the comfort-i trial. ClinicalTrials.gov Identifier: NCT00952289. Updated March 12, 2018. Accessed November 27, 2024. https://www.clinicaltrials.gov/study/NCT00952289

6. Controlled myelofibrosis study with oral janus-associated kinase (jak) inhibitor treatment-ii: the comfort-ii trial. ClinicalTrials.gov Identifier: NCT00934544. August 19, 2019. Accessed November 27, 2024. https://clinicaltrials.gov/study/NCT00934544

7. Kuykendall A, Palandri F, Zhang S, et al. 3804 retrospective real-world analysis of survival outcomes in patients with myelofibrosis and new or worsening anemia treated with ruxolitinib in the united states. Paper presented at: 66th ASH Annual Meeting and Exposition. December 8, 2024. San Diego, CA