Learning From a Multidisciplinary Approach in Graft-Vs-Host Disease

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THE MULTIDISCIPLINARY CARE model has been pursued by many groups in the oncology field to get a wider range of specialists involved in cancer care. It plays a particularly crucial role in rare disease states. These are opportunities where health care professionals with specialized experience outside of medical oncology can contribute their expertise and help shape individualized patient plans.

To address the unique needs of patients with graft-vs-host disease (GVHD), the bone marrow and stem cell transplant program at Memorial Sloan Kettering Cancer Center (MSK) in New York, New York, founded a dedicated multidisciplinary clinic for patients who experience this condition following allogeneic hematopoietic cell transplantation (HCT) for advanced hematologic nonmalignant diseaseses or malignancies. GVHD is a multifaceted complication with symptoms that can involve multiple organs and has limited treatment options, making it vital to consult specialists in disciplines far from hematology and oncology. From diagnosis and treatment selection to rehabilitation and survivorship, a patient’s journey requires close attention.

Peers & Perspectives in Oncology spoke to members of the clinic’s staff to discover how they collaborate to manage the complex manifestations of GVHD and what benefits their approach offers their patients. In this article, we look at the learning experiences that the clinic has provided, and a follow-up article in the upcoming December issue will explore needs and opportunities in GVHD treatment that they have observed.

GVHD DEMANDS PROMPT ACTION

In both acute and chronic GVHD, early diagnosis and treatment can make a difference. “We have also learned that the more advanced GVHD is, the harder it is for patients to have reversibility of their symptoms,” explained Doris M. Ponce, MD, MS, bone marrow transplant specialist and director of MSK’s GVHD program. “The likelihood of having better outcomes and better responses is enhanced with early intervention.”

Andrew Harris, MD, associate attending pediatrician and clinical director for the pediatric multidisciplinary GVHD clinic, said that chronic GVHD can be slow to present and subtle in initial presentation, potentially affecting nearly any organ system in the body. “You have to be well aware of the different manifestations of chronic GVHD and be able to identify some of the more subtle findings or early findings in the disease in order to make a diagnosis and start therapy early.”

If fibrosis caused by GVHD is not controlled, it can persist long after the alloimmune responses are reduced, Harris added. In the long term, patients can need rehabilitation medicine and physical therapy in addition to medication.

USING A MULTIDISCIPLINARY TEAM

When Ponce first recognized an institutional need for multidisciplinary care, she investigated other multidisciplinary models, such as the National Institutes of Health’s Chronic GVHD Study Group under Steven Z. Pavletic, MD, PhD, and The University of Texas MD Anderson Cancer Center’s Multi-Discipline GVHD Clinic and Research Program under Amin M. Alousi, MD. After visiting these programs, she worked to create a model that addressed the needs of MSK’s patients and the availability of its resources. She determined key needs such as a dermatologist, rehabilitation specialist, and nutritionist and reached out to them. “You’d be surprised that if people want to collaborate with you, you just need to knock on the door, establish what team members you need, [and] ask for resources in your institution that might be available to you. If you don’t ask, you don’t get.”

“At many centers, patients are referred out to different subspecialists at some point in their care. When you put a referral to a subspecialist, there’s often a delay in getting in to see [them],” explained Harris. He said that the specialist may only focus on their area instead of the bigger picture, which can lead to an incomplete perspective on the best course of action.

Harris feels this problem can be avoided when specialists interact with each other in addition to seeing the patient. “Then when we make a recommendation, it’s a combined, comprehensive recommendation for therapy,” he said.

In addition to the transplant specialists, MSK’s multidisciplinary GVHD clinic includes experts in dermatology, rehabilitation medicine, dentistry, endocrinology, nutrition, and social work. Harris works with a pulmonologist and a gastroenterologist for pediatric patients as well. Due to MSK’s institutional focus on oncology, their colleagues have experience in applying their disciplines to patients with cancer.

Ponce and Harris said that the GVHD clinic’s patients come in not only from MSK’s transplant program but from referrals across the state and beyond for chronic GVHD. In contrast to seeing his own patients when newly diagnosed, the referrals are often those who have had a slower or less than optimal response to chronic GVHD therapy or worrisome disease features such as scleroderma, pulmonary involvement, or significant disability. They have relationships with transplant programs at other institutions and serves as an liaison with their multidisciplinary team.

On a designated clinic day each month, patients with GVHD come in for a multispecialty assessment in which they are seen by different specialists based on which symptoms of GVHD they have. Ponce said that after a comprehensive assessment, they prepare a treatment plan for the patient and bring their recommendations to the overall team so they can share their expertise. “For each specialty, they bring something unique to the plate,” she said.

Grigory Syrkin, MD, an assistant attending physician who serves the clinic as a rehabilitation medicine specialist, said he meets patients with the transplant physician and sometimes the dermatologist, discusses the case with the nutritionist, and then meets with them all to come up with a joint plan for rehabilitation. They present their conclusions to the patient and the referring physicians, if applicable.

ASSESSMENT AND TREATMENT

When managing GVHD, physicians assess baseline disease and response to agents, aiming for at least partial response to frontline treatment with corticosteroids. Ponce said they also assess quality of life through surveys looking at multiple symptoms such as stress, anxiety, lack of sleep, pain, dry mouth, and discomfort. They found decreases in many symptoms, and in particular stress was significantly decreased, which she took as a positive sign for their contributions. “We hypothesize that patients who are able to get proper care…will decrease their level of distress that can be related to having this kind of complication. That for us is important and also very motivational to continue with our efforts to help our patients.”

For patients who don’t respond to steroids, treatment options are limited. Ruxolitinib ( Jakafi) is approved for use in both acute and chronic GVHD, and ibrutinib (Imbruvica), belumosudil (Rezurock), and, most recently, axatilimab-csfr (Niktimvo) are FDA approved for chronic GVHD. The NCCN lists a variety of unapproved alternative immunosuppressive agents that may be used in specific situations.¹

Alina Markova, MD, MSK’s section head of general dermatology and oncodermatology, said dermatologic GVHD has some of the largest challenges, since there are no topical treatments approved by the FDA for GVHD, and topical steroids can be difficult to get covered by insurance. She said systemic therapy for chronic GVHD can treat the disease incompletely, leaving patients with debilitating symptoms.

Assessing whether skin manifestations are improving over time is also difficult. “Sometimes it’s very easy to understand and diagnose, but other times, especially in sclerotic GVHD, the improvements are slow and gradual, and there are no great tools to diagnose response in these patients,” Markova said. She uses patient reporting of treatment response as well as photographic evidence, with the clinic now employing a 3D photography system that has helped in diagnosing patients.

LEARNING FROM COLLABORATION

The contributing specialists said that since the multidisciplinary clinic’s opening in 2016, they have learned a great deal from their experiences with patients and from working with one another.

Simply being in the same room made a huge difference in multidisciplinary efforts, Ponce discovered. Having specialists in areas other than cancer enables them to share unique insights and develop one another’s understanding of GVHD. She also said they’ve observed similarities to autoimmune complications from immune checkpoint inhibitors used in other disease states, and the recommendations followed in GVHD intersect with those for these agents, showing that the multidisciplinary model is valuable in other scenarios.

Markova added that they learned how to optimize their own specialty in relation to the patient’s needs; for example, prioritizing treatments that will avoid immunosuppression in patients who are at high risk of malignant disease relapse.

Another lesson that experience in the clinic taught was to avoid bringing too many specialists face-to-face with the patient at once, because this was sometimes overwhelming and made them uncomfortable. “We want to keep in mind some of the psychosocial components of being at a multidisciplinary expert clinic where you feel like you’re being examined by so many clinicians in a short period of time,” Markova explained. “While this provides a lot of ease and efficiency, not every patient is comfortable with that concept.”

“I learn new things every single visit, whether it’s a new strategy or thought process from one of these different subspecialists around an area of pathophysiology or dysfunction in a patient,” said Harris. “I’m learning from what they’re doing in patients who have different complications that may manifest similarly from different disease processes. I’ve also learned that there’s a lot that [oncologists] don’t know [and that other physicians] are struggling with these other diseases as well.” He believes there are more opportunities for collaboration across disease types with similar manifestations to GVHD that can be adapted based on their experiences.

Additionally, collaboration has improved their evaluation of adverse event profiles from different medications, since one specialist’s concerns for an organ system may better identify which therapies a patient can tolerate safely. Harris said this feedback has helped shape recommendations for systemic therapy in certain patient cases.

As a physiatrist, Syrkin has grown more aware of avoiding an undue burden on patients who are often malnourished and dealing with fatigue when he devises rehabilitation regimens. He said that over the years, his approach has become more minimalist in response. “I try to give patients the least amount of work that would be effective for the impairments that they face,” he said. He also shares his assessments with patients to encourage them to meet their rehabilitation goals.

CONNECTING WITH THE COMMUNITY

Beyond working closely with one another, MSK physicians are engaged with research and patient care with outside institutions. “The community involved in chronic GVHD research and treatment is small and in close communication,” said Harris. “The bone marrow transplant specialists share information and bring that back to the other team members with organ-specific concerns.”

With their focus on quality of life and recovery, the clinic’s staff are mindful of what comes next after successful management of GVHD.

“The multidisciplinary approach really does take a village. That often includes not just the patient, but also their caregiver and anyone in their social support network,” said Syrkin. “It further strengthened my belief that we do need the holistic approach to successfully manage challenges posed by the complications of GVHD.”

Markova stressed that although most of their practice is dedicated to acutely ill patients with symptomatic GVHD, their expertise and care continue to benefit patients even when the disease is well controlled and into survivorship. She said they can offer quality-of-life improvements and restorative oncodermatology with tools such as laser treatment to improve range of motion and chemical peels to restore dyspigmentation.

Many of the pediatric patients treated by Harris were referred from regions far from MSK. In his experience, having experts in the field provides resources that can help provide care locally for some patients. “Relocating to another place is very detrimental socioeconomically for families and for patients,” he said. “Having those people you can partner with who can help provide guidance and education and assist with management remotely can go a long way to improving comfort with taking care of some of these patient [cases].”

Providing a high level of care can facilitate patients going back to their community and collaborating with their local physician, Ponce said. Patients receiving HCT ideally return to the referring practice as soon as possible, but complications such as GVHD can force them to return to a specialized center. Ponce feels this should be an important consideration in their care plans. “It’s possible to collaborate with their community clinician and allow the patient to get back to their life, get back to their community, and use collaborative efforts to care for patients.”

_REFERENCE

_{1. NCCN. Clinical Practice Guidelines in Oncology: Hematopoietic Cell Transplantation (HCT), version 2.2024. Accessed October 14, 2024. https://tinyurl.com/3dt3sufs}