AGAVE-201: Axatilimab for cGVHD

Video content above is prompted by the following:

Axatilimab is pending FDA approval for cGVHD after failure of at least 2 prior lines of systemic therapy. Discuss its mechanism of action (MOA) and how this MOA might add value to cGVHD treatment landscape.

Discuss phase 1/2 data (Kitko CL, et al. 

. 2022) and AGAVE-201 trial data with axatilimab for cGVHD (Wolff D, et al. ASH 2023). 

Videos

Medical experts discuss the mechanism of action within axatilimab. 

Recent Updates: REACH3, ROCKstar, and RWD

Briefly discuss recent updates presented at ASH 2023 and TANDEM 2024: 

3-year follow-up of the ROCKstar study, TANDEM 2024

Brie fly discuss available real-world data (RWD) with ruxolitinib (Spałek A, et al. 

Medical experts discuss the recent updates presented at ASH 2023 and TANDEM 2024. 

Clinical Scenario: Treatment Selection in the third line and beyond in cGVHD

Dr Holtan: Please read this clinical scenario:

 Four months after having undergone allogenic hematopoietic stem transplant, a patient presents to the clinic with rashes over a large portion of his body and dry eyes. Based on clinical presentation and lab results, a diagnosis of moderate cGVHD is established. Patient was treated with steroids and subsequent calcineurin inhibitors for 4 to 6 weeks but showed little improvement in cGVHD symptoms.

What other treatments could be used in such patients once steroid refractoriness is established?

Are there factors you consider when choosing an alternate treatment option (efficacy, safety profile, clinical manifestations)?

Medical experts discuss treatment selection for a specific clinical scenario. 

Considerations for Third-Line Treatment in Chronic GVHD

 For patients showing inadequate response to second-line therapies, what factors guide your treatment selection in third line and beyond?

Please discuss the role of safety concerns, organ involvement, severity, etc, in your decision to use one agent over another.

Medical experts discuss considerations for third-line treatment in chronic GVHD. 

Overview of the ROCKstar Study

Please review data that led to belumosudil’s FDA approval (Jagasia M, et al. 

Efficacy data (duration of effect, need for additional treatments, data on decrease in formation of scar tissue and decrease in immune cell activity, etc).

Safety profile of belumosudil and adverse effect management.

Medical experts discuss the data that led to belumosudil’s FDA approval. 

Overview of Advanced Therapies in cGVHD

Both ruxolitinib and ibrutinib are approved for use in cases of cGVHD that have failed 1 or more lines of systemic therapy.

Briefly summarize and critique clinical trial data with ruxolitinib (REACH3) and ibrutinib (Miklos D, et al. 

Comment on adverse effects most frequently seen with ruxolitinib and ibrutinib and how you manage them.

In which patients would you hesitate to use ruxolitinib or ibrutinib (eg, patients at risk of developing thrombocytopenia, etc)?

Belumosudil is approved for treatment of cGVHD after failure of 2 or more systemic therapies. Can you elaborate on anti-inflammatory and antifibrotic properties of belumosudil and results from preclinical and human studies in reduction of fibrosis (Flynn R, et al. 

How do these properties distinguish belumosudil from other targeted therapies for cGVHD?

Medical experts discuss advanced therapies in cGVHD. 

Navigating Treatment Decisions in Chronic GVHD

What are the criteria for switching to another treatment?

How do you establish that the patient is not responding well to steroids/is steroid-refractory?

How long should one wait before switching to a second-line treatment?

How do you choose between available treatment options after initial treatment in the second line?

Medical experts discuss criteria for switching GVHD treatments and how to choose between available treatment options. 

Optimizing Chronic GVHD Therapy

What are your overall goals for cGVHD treatment? 

Corticosteroids are used for initial treatment for chronic GVHD. What are the primary concerns with their long-term use?

Medical experts discuss overall goals for cGVHD treatment as well as concerns with long-term corticosteroid use in treatment. 

Navigating Chronic GVHD: Phases of Pathophysiology and Best Practices in Patient Monitoring

 Please address the 3 phases of pathophysiology of cGVHD (early inflammation, chronic inflammation and dysregulated immunity, and aberrant repair and fibrosis) and the interplay between them.

How does inflammation affect different organs? And fibrosis?

After confirmed diagnosis, please share your monitoring routine for patients with cGVHD.

Are there certain symptom scores (eg, Lee skin symptom score) that are associated with better clinical outcomes?

How do you share responsibility across subspecialty to monitor patients? Or other HCPS?

Medical experts discuss navigating chronic GVHD.

Differentiating Acute and Chronic Graft-vs-Host Disease

Is the time of onset the main distinction between acute and chronic graft-vs-host disease (cGVHD), or it is symptoms at clinical presentations as well? Please elaborate on tissues impacted.

After a brief introduction, Shernan Holtan, MD, and Haris Ali, MD, discuss the distinction between acute and chronic graft-vs-host disease. 

Shernan Holtan, MD

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