Biopharma expert Ivan Kairatov joins us today to discuss a paradigm shift in evaluating cutaneous chronic graft-versus-host disease (cGVHD), a severe complication of stem cell transplantation. Drawing from his work with an international NIH task force, he explains why current assessment standards often fail to capture meaningful patient improvements and how a proposed new framework aims to fix this. Our conversation will explore the critical distinction between different skin symptoms, the integration of patient-focused metrics, and the urgent push to incorporate molecular-level biomarkers into clinical practice, moving beyond what the naked eye can see.
Under previous assessment standards, a patient’s skin could become much more flexible, yet the treatment might have been deemed unsuccessful in a clinical trial. How did this discrepancy impact drug development, and what’s a real-world example of a patient improvement that might have been overlooked?
This was a profoundly frustrating and misleading aspect of the 2014 criteria. It created a bottleneck in drug development because promising therapies were potentially being discarded. Imagine a patient suffering from sclerosis, where their skin feels like hardened leather, restricting movement and causing pain. After treatment, their skin could become significantly softer, more pliable, allowing them to finally flex their elbow or make a fist without pain. For that individual, the improvement is life-changing. However, if the total surface area of the affected skin didn’t shrink past a certain rigid statistical threshold, the trial would officially record the treatment as a failure. This disconnect between a patient’s lived experience and the trial’s conclusion meant we were likely missing out on effective treatments.
The proposed framework separates scoring for rash-like symptoms and deep-tissue hardening. Why is this distinction so critical for evaluating treatment response? Could you walk us through how a clinician would use these two different rubrics to assess a patient’s progress over time?
This separation is absolutely essential because we’re talking about two very different biological processes that respond to therapies at different paces. A rash is an epidermal, or surface-level, inflammation that might respond relatively quickly to a treatment. Sclerosis, on the other hand, is a deep-tissue hardening—a fibrotic process—that can take much longer to show improvement. Lumping them together is like trying to measure the speed of a sprinter and a marathon runner with the same stopwatch over 100 meters; it just doesn’t make sense. A clinician using the new rubrics would, at each visit, score the rash on its own scale for redness and irritation, and separately assess the sclerosis, perhaps noting changes in skin tightness and flexibility. This dual-track approach allows us to see if a drug is excellent for calming inflammation but slower on fibrosis, or vice-versa, giving us a far more accurate and nuanced picture of its true effect.
New guidelines introduce scales for skin quality and the disease’s impact on a patient’s daily life, moving beyond just measuring the affected area. How do these patient-focused metrics provide a more complete picture, and how will this data change conversations about treatment goals?
These metrics bring the patient’s actual experience from the periphery to the very center of the assessment. Simply measuring the square centimeters of affected skin tells you nothing about the person’s quality of life. Is the skin so tight they can’t lift their arms to hug a loved one? Is the itching so severe it disrupts their sleep? By adding scales for skin softness, tightness, and the impact on daily functions, we are finally capturing the data that truly matters. This fundamentally changes the conversation about treatment goals. Instead of just saying, “Let’s reduce the affected area by 25%,” the goal can become, “Let’s improve your skin’s flexibility so you can return to gardening,” or “Let’s reduce the itch so you can sleep through the night.” It makes the treatment goal collaborative, personal, and far more meaningful.
You’ve called for medicine to move beyond naked-eye observation by using biomarkers like protein markers for fibrosis and T-cells. What are the key steps required to integrate this molecular-level analysis into standard clinical practice, and what barriers do you foresee in this process?
The call to action is to fundamentally shift our diagnostic and monitoring paradigm from what we can see to what we can measure at a molecular level. The first key step is standardizing the collection of blood and skin samples during treatment, which is not currently routine. We need to build robust, validated assays to consistently measure protein markers of inflammation and fibrosis, and to analyze immune cell populations like T-cells. A major barrier is logistical and financial; setting up this infrastructure across multiple clinical sites requires significant investment and training. Another challenge is data interpretation—we need to build large datasets to understand what a change in a specific biomarker truly means for a patient’s long-term prognosis. It’s a huge undertaking, but it’s the only way to make treatment truly predictive and personalized.
Minimally invasive techniques like “skin-tape stripping” could make biomarker collection easier for patients. Can you explain this process and compare its potential diagnostic value to more traditional methods like blood draws or biopsies? Please provide specific details on its benefits.
Skin-tape stripping is a wonderfully innovative and patient-friendly technique. It’s as simple as it sounds: a special adhesive tape is pressed onto the skin and then gently removed, lifting away the outermost layers of skin cells and the proteins and immune markers present there. Unlike a punch biopsy, which is a minor surgical procedure that leaves a scar and can be painful, this is completely non-invasive. Compared to a blood draw, which gives a systemic overview, tape stripping provides a direct, localized snapshot of the disease activity right at the site of inflammation. This could allow us to track the molecular response to a topical treatment with incredible precision, without ever needing a needle or a scalpel. The benefits are enormous: less pain, no scarring, and the potential for more frequent sampling to closely monitor treatment efficacy.
What is your forecast for the treatment of cutaneous chronic graft-versus-host disease?
My forecast is one of cautious but profound optimism. I believe we are on the cusp of moving from a reactive to a predictive and precise era of cGVHD care. The refined assessment criteria will sharpen our clinical trials, ensuring that truly effective drugs are recognized and advanced. In parallel, the integration of biomarkers will be the real game-changer. Within the next decade, I envision a future where we can use a simple skin or blood test to identify patients at high risk before severe symptoms even develop, and then select the most effective therapy for them based on their unique molecular profile. We will be treating the underlying biology of the disease, not just the visible symptoms, leading to more durable responses and a dramatically improved quality of life for all patients.
