Axatilimab: Uses, Dosage, Side Effects and Interactions

Axatilimab is a novel monoclonal antibody treatment that has gained attention for its promising results in patients with chronic graft-versus-host disease (cGVHD), particularly those who have not responded to multiple previous therapies. As a first-in-class inhibitor targeting the CSF-1 receptor (CSF-1R), axatilimab disrupts pathways central to inflammation and fibrosis seen in cGVHD. This article provides a comprehensive overview of axatilimab’s uses, optimal dosing strategies, potential side effects, and what is currently known about its drug interactions, based on the latest clinical research.

Uses of Axatilimab

Axatilimab represents a new wave of targeted therapy, specifically designed for patients grappling with chronic graft-versus-host disease (cGVHD), a complex and often debilitating condition that can arise after allogeneic stem cell transplantation. Let’s explore how axatilimab is being used and what makes it such a significant development for patients and clinicians.

Indication	Patient Population	Clinical Results	Source
cGVHD	Refractory/Relapsed	50–74% response rates	1 2 3 4
Organ Involvement	Lung, joints/fascia, skin, esophagus	Responses observed in all major organs	2 3 4
Symptom Relief	Patients with high symptom burden	41–69% reported major symptom improvement	3 4

Table 1: Clinical Uses and Efficacy of Axatilimab

Overview of Axatilimab’s Indications

Axatilimab is primarily being developed and used for chronic graft-versus-host disease (cGVHD) in patients who have failed two or more lines of systemic therapy. These patients are often highly symptomatic and have limited options, as standard immunosuppressive therapies can be associated with significant toxicity and risk of infections 1 2 3 4.

Mechanism of Action and Clinical Rationale

Axatilimab is a fully humanized IgG4 monoclonal antibody that binds with high affinity to CSF-1R on the surfaces of monocytes and macrophages. By blocking CSF-1R and its activation by ligands CSF-1 and IL-34, axatilimab prevents the migration, proliferation, and survival of these immune cells—processes known to drive both inflammation and fibrosis in cGVHD 1 2 3 4. This unique mechanism distinguishes axatilimab from other cGVHD therapies that primarily target lymphocytes.

Clinical Results and Organ-Specific Benefits

Across multiple phase 1 and phase 2 studies—including the pivotal AGAVE-201 trial—axatilimab has demonstrated robust overall response rates (ORR) of 50–74% in heavily pretreated cGVHD patients 3 4. Notably:

• Lungs: Up to 47% response in patients with pulmonary involvement, a notoriously challenging manifestation to treat 4.
• Joints/Fascia: High response rates (over 75% in some cohorts) in patients with fibrotic joint and fascia disease 4.
• Other Organs: Meaningful improvements also observed in skin, esophagus, and eyes 2 4.

Symptom Relief and Quality of Life

A key secondary endpoint in clinical trials has been the reduction of symptom burden, as measured by the modified Lee Symptom Scale. Between 41% and 69% of patients reported a clinically meaningful improvement (≥5–7 point reduction) in symptoms, highlighting not just organ response but also improved daily functioning 3 4.

Dosage of Axatilimab

Choosing the right dose of axatilimab is crucial to balancing efficacy and safety. Clinical trials have explored a range of dosing regimens, and recent research points toward an optimal balance between effectiveness and tolerability.

Dose (mg/kg)	Frequency	Response Rate	Discontinuation Due to AEs	Source
0.3	Every 2 weeks	74%	6%	3 4
1	Every 2 weeks	67%	22%	3 4
3	Every 4 weeks	50%	18%	3 4

Table 2: Summary of Axatilimab Dosing Regimens and Outcomes

Dosing Strategies Explored

Clinical studies have evaluated three main dosing regimens:

• 0.3 mg/kg every 2 weeks
• 1 mg/kg every 2 weeks
• 3 mg/kg every 4 weeks 3 4

All doses are administered intravenously, with dosing cycles typically lasting 28 days.

Efficacy and Dose-Response Relationship

While all three doses showed meaningful clinical activity, the 0.3 mg/kg every 2 weeks group achieved the highest overall response rate (74%) and the most favorable safety profile 3 4. The 1 mg/kg and 3 mg/kg groups also demonstrated clinical benefit, but with a trend toward higher adverse event-related discontinuations.

Patient Selection and Dose Adjustment

Patients enrolled in these studies were generally those who had failed multiple prior therapies (median of 4–5 previous lines) and had multi-organ involvement 2 4. Dose reductions were allowed in response to adverse events, and some patients responded to lower doses after initial higher-dose exposure 1 2.

Practical Considerations

• Administration: Axatilimab is given as an intravenous infusion in a hospital or clinical setting.
• Duration: Patients typically continue therapy as long as clinical benefit is observed and side effects are manageable 3 4.
• Dose Adjustments: Temporary interruption or reduction may be required in case of significant lab abnormalities or symptoms 1 2 3.

Side Effects of Axatilimab

Understanding the side effect profile of axatilimab is essential for clinicians and patients to make informed decisions about therapy. While axatilimab appears generally well-tolerated, certain side effects are common and dose-dependent.

Side Effect	Frequency (All Grades)	Severe (Grade ≥3)	Notes/Mechanism	Source
Lab abnormalities (AST, CPK, ALT, lipase)	Dose-dependent (up to 67% for CPK at highest dose)	8–13% at 1mg/kg; higher at 3mg/kg	Transient, not linked to organ damage	1 2 3 4
Periorbital edema	8–50%	Rarely severe	More common at higher doses	1 2 3
Hypersensitivity	Rare	Grade 3 reported	Infusion-related reactions	2 3
Infections	Low risk	None severe	No viral reactivation observed	2 3
Other (myositis, elevated enzymes, edema)	Occasional	Grade 4 myositis, rare	Usually reversible	1 2

Table 3: Common Side Effects of Axatilimab in Clinical Trials

Laboratory Abnormalities

The most frequently observed side effects are transient increases in liver enzymes (AST, ALT), creatine phosphokinase (CPK), and lipase. These laboratory changes are dose-dependent but generally not associated with clinical symptoms or organ toxicity. They are believed to result from axatilimab’s inhibition of CSF-1R on liver macrophages (Kupffer cells), which alters enzyme clearance 1 2 3 4.

• Key point: These abnormalities are usually asymptomatic and reversible upon dose adjustment or discontinuation.

Edema

Periorbital (around-the-eye) edema is a recognized class effect of CSF-1R inhibitors. It tends to be mild (grade 1–2) and more common at higher doses (up to 50% with 3 mg/kg every 4 weeks) 2 3. Severe edema is rare and can be managed with supportive care and/or dose reduction.

Hypersensitivity and Infusion Reactions

Infusion-related hypersensitivity reactions have been reported, including rare grade 3 (severe) cases. These reactions are manageable with standard protocols for monoclonal antibody infusions 2 3.

Infections

Unlike many other cGVHD treatments, axatilimab has not been associated with a significant increase in infections or viral reactivation (e.g., cytomegalovirus, Epstein-Barr, herpes simplex) 2 3. This suggests a favorable safety profile compared to broader immunosuppressive agents.

Rare and Serious Events

• Isolated cases of myositis (muscle inflammation) and severe enzyme elevations have been noted, generally at higher doses 1 2.
• A small percentage of patients discontinued therapy due to adverse events: 6% at 0.3 mg/kg, 22% at 1 mg/kg, 18% at 3 mg/kg 3 4.

Interactions of Axatilimab

Drug interactions are a critical consideration, especially for patients on multiple therapies. Clinical and preclinical data indicate that axatilimab has a low potential for significant drug-drug interactions, but some caveats are worth noting.

Type	Interaction Observed	Clinical Impact	Source
CYP enzyme	None reported	Minimal	1 2 3 4
Transporters	Not a significant substrate/inhibitor	Low risk	5
Immunosuppressants	No observed increased infections or viral reactivation	Safe with other cGVHD drugs	2 3 4
GI Interactions	Not likely	Low risk	5

Table 4: Overview of Axatilimab Drug Interaction Profile

Metabolic and Transporter Interactions

• Metabolism: Axatilimab, as a monoclonal antibody, is degraded via proteolytic pathways and is not metabolized by CYP enzymes, reducing the risk of traditional drug-drug interactions 1 2 3 4.
• Transporters: Unlike small molecules like axitinib, which can interact with P-glycoprotein (P-gp) and other transporters, axatilimab does not exhibit significant transporter-mediated interactions 5. (Note: Source 5 focuses on axitinib, not axatilimab, but highlights the general low risk for mAbs.)

Co-administration with Other Medications

• Immunosuppressants: Patients in clinical trials were often on concurrent immunosuppressive regimens. No increased risk of infection or viral reactivation was observed, indicating axatilimab can be safely combined with other standard cGVHD medications 2 3 4.
• Other Drugs: No data currently suggest the need for dose adjustments or concern for interactions with commonly used supportive medications.

Patient Considerations

• Polypharmacy: As with all new therapies, clinicians should remain vigilant when prescribing axatilimab to patients on extensive medication regimens, but the clinical trial data are reassuring regarding interaction risks.

Conclusion

Axatilimab is a promising, targeted addition to the treatment landscape for chronic graft-versus-host disease, especially in patients who have exhausted other options. Here are the key takeaways:

• Targeted use: Axatilimab is indicated for patients with cGVHD who have failed two or more prior therapies, showing high and durable response rates across organ systems 1 2 3 4.
• Flexible dosing: The 0.3 mg/kg every 2 weeks regimen offers the best efficacy-safety balance, with higher doses also effective but associated with more side effects 3 4.
• Manageable side effects: Most adverse events are transient lab abnormalities or mild edema, with serious side effects being rare and manageable 1 2 3 4.
• Low interaction risk: Axatilimab is unlikely to cause significant drug-drug interactions, making it a safe choice for patients with complex medication regimens 1 2 3 4 5.

In summary:

• Axatilimab fills an unmet need for refractory cGVHD.
• It works via a unique, non-lymphocyte-targeting mechanism.
• The optimal dose balances potent efficacy and tolerability.
• Side effects are mostly mild and manageable.
• Drug interaction risk is low, supporting its use in complex patients.

As clinical experience with axatilimab expands, its role in cGVHD and potentially other fibrotic and inflammatory diseases will become clearer—holding promise for patients in need of new hope.