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Oncology Nation

1yr
Tackling fibrosis in cGVHD

Chronic graft-versus-host disease (cGVHD) involves multiorgan pathology, with features of both inflammation and fibrosis. The innate and adaptive immune systems likely contribute to the cause of this condition. Experts suggest that the acute inflammatory response secondary to tissue injury early posttransplant transforms to chronic inflammation and dysregulation of T and B cells. Thus, leading to impaired tissue repair and fibrotic reactions. Chronic GVHD can lead to multisystem tissue damage , with the mucosa, skin, and lung most affected. Following allogeneic HSCT, cGVHD is a leading cause of late morbidity and late non-relapsed mortality.

Although fibrosis may contribute to wound healing in some chronic inflammatory conditions, in cGVHD, it leads to chronic disability when it impacts the joints or substantial areas of skin. Fibrosis can result in life-threatening chronic respiratory deficiency when it affects the peribronchiolar pulmonary lobules. Fibrosis typically responds poorly to treatment once it is entrenched .

How do you manage fibrosis in patients with chronic GVHD following the failure of systemic therapies?

  • 1yr
    A MDT approach is key. Will start with supportive therapies lik PT for stiff joints. Typically I start with steroids both topical and systemic for mild to moderate cGVHD. Other therapies usch as Rux, Myfortic and Prograf can be used and most recently Rezurock which has been approved.
  • 1yr
    Steroids and jakafi, ritux or imbruvica based on comorbidities, then Rezurock as last line resort
  • 1yr
    Agree with multidisciplinary approach as well as consideration for prednisone and ruxolitinib
  • 1yr
    Treatment of fibrosis requires a multifaceted approach. Fibrosis of the skin and joints can be quite debilitating for patients. My first go to line therapy is often steroids followed by Ruxolitinib. More recently Rezurock throught trials has shown to be more efficacious in targeting fibrosis. As we become more familiar with using Rezurock I am sure this will be a useful tool to combating GVHD and fibrosis.
  • 1yr
    Multidisciplinary approach. First line is steroids then ruxolitinib followed by Rezurock if needed.
  • 1yr
    It’s hard situation to manage. Multidisiplinary managers helpful including pharmaceutical interventions, physical therapy and supportive care etc.
  • 1yr
    Pirfenidone, Tyrosine kinase inhibitors (TKIs) have been shown to inhibit two different profibrotic pathways (transforming growth factor β [TGF-β] and platelet-derived growth factor [PDGF]) in various mouse models of fibrotic disease, and offer a possible novel treatment approach for cGVHD patients suffering from severe sclerosis
  • 1yr
    Unfortunately very heard to treat once scleroderma and oral mucosal, pulmanary ( rare but often fatal) sets in- very hard to reverse - early PT, systemic therapies such as JAK2/ ROCK inhibitors , photpheresis, SIrolimus early on would help. Physical activity would help, early detection is prudent. Very poor quality and often limits quality and lead to depression- need to be monitored for.
  • 1yr
    this must involve several specialties as cGVHD can be tricky to identify and treat. we usually give systemic steroids followed most often by Jakafi. Rezurock is a newer option but i don't have experience with this drug. other drugs include cyclosporine and tacrolimus but i will always have the transplant team involved to make primary decisions.
  • 1yr
    multitude of therapies are now available ,each pt needs to be individualized as to what works better for them ,need to watch for organ dysfn and sec malignancies
  • 1yr
    I agree with the statements of my colleagues and have really nothing to add except one must always be aggressive in your thinking and incorporate as many of your associates as needed to reach a successful conclusion.
  • 1yr
    Pt and ot help patients. Using medications to treat chronic gvhd is also useful. Massage can help too.
  • 1yr
    I would favor Myfortic and Prograf. If it proves refractory to both of these drugs, then I would initiate a trial of Prednisone.
  • 1yr
    There must be a multifaceted and multidisclipinary approach to treatment of cGVHD as the effects can be severe and affect multiple organ systems. First line therapy is systemic steroids followed most often by Jakafi. The newly approved treatment Rezurock works by downregulating infallmation and fibrosis through the inhibition of the ROCK2 pathway. This therapy can be patients dealing with major issues of fibrosis. Also for targeting skin fibrosis in particular topical therapies can be effective, such as steroids, cyclosporine, and tacrolimus.
  • 2yr
    For conjunctival fibrosis in the setting of ocular GVHD, active inflammation must be suppressed with aggressive topical and/or systemic steroids followed by a slow taper. Some patients require longterm topical immunosuppressive therapy with corticosteroids or alternatively off-label usage of compounded cyclosporine 1% or tacrolimus 0.2 to 0.1%. Once conjunctival scarring has formed, there are not many options to reverse it so prevention is key.
  • 2yr
    Early recognition and treatment are key factors in the outcome of fibrosis. The patients who failed systemic corticosteroids should start second-line therapy without delays. My second-line therapy of choice is ruxolitinib. If unable to achieve a response or if suboptimal, I will select belumosudil as my next agent. Corticosteroid taper should be part of the plan as well as physical therapy w/ stretching exercises. It is unlikely that patients will achieve complete reversibility of their skin changes, but overall improvement that allows joint mobility may be achieved.
  • 2yr
    Multidisciplinary management is key when it comes to cGVHD. For moderate to severe cGVHD, systemic prednisone remains the main treatment. Ruxolitinib and belumosudil are both approved and relatively well tolerated. Belumosudil has some anti-fibrotic properties and might be efficacious against fibrosis of the skin and the lung. In addition, ancillary treatments of cGVHD are paramount such PT, eye drops, stretching, local corticosteroids etc
  • 2yr
    Continued immunosuppression with drugs including tacrolimus, mycophenolate. Glucocorticoids generally less useful especially along, may be used in high doses for acute exacerbations.
  • 2yr
    The options of supportive care, including physical therapy.
    Pharmaceutical options include belumosudil which can control chronic inflammation and fibrosis, and the Jak 2 inhibitor Ruxolitinib.
    Close follow-up for secondary malignancies

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