How Axatilimab Is Advancing Chronic Graft-Versus-Host Disease Management

Corticosteroids are typically the first line of treatment for patients newly diagnosed with chronic graft-versus-host disease (cGVHD), and while there is no standard second-line therapy in cGVHD treatment, early escalation and steroid-sparing options are prioritized when patients are not meeting treatment goals.¹  

Axatilimab-csfr monoclonal antibody is approved for treating chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapies in adults and pediatric patients weighing at least 40 kg.¹ It works by binding to the colony-stimulating factor 1 receptors (CSF1R) expressed on monocytes and macrophages and reducing the levels of these circulating proinflammatory and profibrotic monocytes and monocyte-derived macrophages.²  

What the Pivotal Trial Shows 

The AGAVE201 study was a phase 2, multinational, randomized trial that evaluated the efficacy and safety of axatilimab-csfr at three different doses in three groups of patients (a total of 241, in three roughly equal-sized groups) with recurrent or refractory cGVHD.³ Trial results indicated that the primary endpoint was met in all three of the trial groups.³ Each group also showed clinically meaningful symptom improvement on the modified Lee Symptom Scale.³ Patient responses were rapid, and a majority had a maintained response at 12 months.³ A number of patients receiving baseline glucocorticoids were able to reduce or discontinue their doses by cycle 7 day 1, underscoring the drug’s steroid-sparing potential.³  

Efficacy Reflected in the US Label 

The US Prescribing Information for axatilimab-csfr indicates that the approved dose of 0.3 mg/kg every 2 weeks has an overall response rate (ORR) of 75%, 95% CI [64, 84], with a median time to first response of 1.5 months, and a more than 7 point decrease in the modified LSS score through cycle 7 day 1 in 56% of patients.¹ Axatilimab-csfr is administered as a 30-minute IV infusion every 2 weeks (max 35-mg per dose) until progression or unacceptable toxicity.¹  

Safety Profile and Monitoring 

The most common adverse events among patients who received at least one dose was transient laboratory abnormalities associated with Kupffer cell depletion induced by CSF-1R blockade, with increasing incidence and grading associated with larger doses. Other adverse reactions included pperiorbital edema.; Discontinuation due to adverse events occurred in 6%, 22%, and 18% in the 0.3 mg/kg every 2 weeks, 1 mg/kg every 2 weeks, and 3 mg/kg every 4 weeks groups, respectively.³ The label recommends monitoring liver, muscle, and pancreatic enzymes at initiation and periodically thereafter, and outlines dose modifications for laboratory elevations and infusion-related reactions.¹  

Positioning Axatilimab-Csfr in Practice 

The FDA has approved four systemic therapeutic options for steroid-refractory cGVHD.² Factors such as organ involvement, comorbidities, logistics, and prior therapies should be considered when determining the best fit for the patient.² JAKAFI^® (ruxolitinib) is indicated after failure of one or two prior lines of therapy and is commonly used as a second line.⁴ IMBRUVICA^®(ibrutinib) is indicated for adult and pediatric patients older than 1 year after failure of one or more lines of systemic therapy.⁵ REZUROCK® (belumosudil) is indicated after failure of two or more prior lines of therapy.⁶  

Clinical Takeaways  

For patients not meeting goals on corticosteroids and ruxolitinib —particularly those with evolving fibrotic phenotypes—axatilimab-csfr  offers a potential  third and fourth-line option that provides rapid, durable responses and symptom improvement, and a safety profile that is readily monitorable.^2,3 Early recognition of nonresponse and fibrotic trajectories, close symptom tracking, and disciplined laboratory monitoring enable timely integration of axatilimab-csfr to change disease course and reduce steroid exposure.^1,3 

References: 

1. NCCN Clinical Practice Guidelines in Oncology National Comprehensive Cancer Network (NCCN Guidelines®) for Hematopoietic Cell Transplantation GraftVersusHost Disease. V.1.2025.  
2. NIKTIMVO TM (axatilimabcsfr). Prescribing information. Incyte; 2025. 
3. Wolff D, Cutler C, Lee SJ, et al. Axatilimab in recurrent or refractory chronic graft-versus-host disease. N Engl J Med. 2024;391:10021014. doi:10.1056/NEJMoa2401537 
4. JAKAFI (ruxolitinib). Prescribing information. Revised 01/2023.  
5. IMBRUVICA (ibrutinib). Prescribing information. Revised 12/2024.  
6. REZUROCK (belumosudil) Prescribing information. Revised 04/2025.