Multidisciplinary GVHD Care Reveals Unmet Needs and Opportunities

IN OUR PREVIOUS issue, we spoke to members of a multidisciplinary team at Memorial Sloan Kettering Cancer Center (MSK) in New York, New York, and reported on the advantages and learning experiences of their dedicated clinic for treating graft-vs-host disease (GVHD). They saw benefits from seeing patients together with specialists, such as crafting individualized treatment plans and reducing the burden on bone marrow transplant physicians and patients. These physicians also shared their perspectives on various barriers in treating acute and chronic GVHD and the trends they see in the field from their cutting-edge standpoint.

Diagnosing patients and applying care early after an allogeneic hematopoietic cell transplant is crucial in patients with GVHD. New therapies are always needed for steroid-refractory disease, allow physicians to customize treatment to the patient’s unique needs, and can be used in pediatric care. Additionally, MSK’s staff observed underutilization of services ranging from rehabilitation to telehealth and suggested steps that can be taken to ensure patients are getting the best possible care.

NEEDS IN DIAGNOSIS AND MONITORING RESPONSE

The multidisciplinary clinic connects patients with specialists who can apply their expertise in a particular organ involved in GVHD or a related area, providing a multispecialty approach with the bone marrow transplant specialist. Their recommendations for localized therapy can also shape the approach to systemic therapy. “We make a composite opinion of whether or not we should be escalating therapy, and then we talk about what our different treatments are available to a patient but has not yet seen, or we feel have not been given sufficient opportunity to show a response to and make recommendations based on that for what would be the next line of systemic therapy for a patient,” said Andrew Harris, MD, associate attending pediatrician and clinical director for the pediatric multidisciplinary GVHD clinic.

Because GVHD can affect patients in many ways, challenges arise when pinpointing and monitoring specific manifestations. Harris said that GVHD of the lung is more challenging to diagnose in pediatric cases since pulmonary function testing can’t be performed or may not provide reliable results in young children. Other testing modalities are being studied to supplement or replace pulmonary function testing in young patients where it is ineffective to diagnose GVHD.

Alina Markova, MD, MSK’s section head of general dermatology and oncodermatology, said that localized therapy for skin GVHD often reaches a limit, at which point the patient must depend on systemic therapy. “That’s when I…leverage the bone marrow transplant physician and explain the limitations that I have…and I need support from the systemic side to help this patient. They will rely on our input on that [manifestation].” She said she can advise on whether GVHD of the skin, mouth, or mucosa is improving or worsening so the group can decide on a systemic therapy approach, but they still need more treatment options.

Another unmet need is for biomarkers that could help assess whether GVHD processes are ongoing or if manifestations are sequelae of GVHD that are no longer active, Harris explained. Without validated tests to guide treatment decisions, they will taper systemic therapy slowly and look for signs of disease recurrence or progression when they think a patient’s GVHD is controlled without knowing what to expect.

“Taking patients off of therapy is a period of a lot of anxiety for all of us because we don’t have a good way of assessing whether or not patients are going to do well or if they’re going to have a flareup and worsening of their GVHD,” said Harris. There is active research into such biomarkers to aid in treatment decisions, although none have been validated and approved.

OPPORTUNITIES FOR BETTER REHABILITATION

Restoration of physical functions impaired by GVHD is a crucial aspect of MSK’s GVHD clinic. Grigory Syrkin, MD, an assistant attending physician and rehabilitation medicine specialist at the clinic, describes the many challenges of rehabilitating patients. He evaluates patients who need a path to recovery with the bone marrow transplant physician and dermatologist and discusses their cases further with the nutritionist.

Syrkin said the nature of the impairments that patients with GVHD experience is multifactorial. It can begin at the level of their mitochondria and end up affecting bones and joints, with additional effects on appetite and nutritional absorption that limit their ability to do recommended exercises. This also means Syrkin needs to consider the physical activity he recommends carefully. He noted that they can also have comorbid neurologic issues that also present safety challenges. Keeping these limits in mind when advising on a patient’s comprehensive care is essential for his role.

Besides these limitations, Syrkin sees opportunities for more use of rehabilitation in cancer care, observing that specialized rehabilitation services are vastly underutilized in the oncology population in general. “Even in rehabilitation circles, there are some practitioners who have this fear of treating patients with cancer, especially treating [those] who may have underlying lytic lesions,” he said.

In the past 5 years, there has been increased awareness of physical activity’s role in both quality of life and survival outcomes, according to Syrkin. “I think the data speak very clearly that better physical function translates into better survival with better quality of life and improved [adherence to] treatment.”

Guidelines recommend that cancer survivors, particularly those with lytic bone lesions and orthopedic or neurologic impairments, be screened by an appropriately trained professional before participation in physical activity. However, Syrkin observed that most oncologists are uncomfortable providing specific physical activity advice. “My recommendation is that oncologists should utilize their locally available cancer rehabilitation physiatrists or physical therapists who have had appropriate training in working with the cancer population.”

TELEMEDICINE EXPANDS ACCESS

To the MSK GVHD clinic’s physicians, it’s imperative to provide greater access to their resources for the patients who need them, and they take referrals from across New York State and beyond for complex chronic GVHD cases. “This is a very rare orphan disease,” Harris said. “Not every transplanter has a lot of comfort in managing it, so having people dedicated to treating is…important. Being a resource not only for patients but for the transplant community and to our colleagues from around the region or around the state…is very important.”

The clinic has seen favorable results since launching its telemedicine platform during the COVID-19 pandemic, said Doris M. Ponce, MD, MS, bone marrow transplant specialist and director of MSK’s GVHD program. It has helped patients get care more conveniently, avoiding travel time and expenses that were a burden on them. Interestingly, Ponce observed a shift in clinic visit rates based on gender. Only 32% of patients who came in person were female, whereas 41% were female for telehealth appointments, which could point to female patients with GVHD having less availability for in-person visits to the multidisciplinary GVHD clinic.

Assessing patients with telemedicine can be challenging, but physicians have adapted to this approach. Markova said that although a dermatologic examination uses visuals and touch, “if a patient is able to send photos and perform basic range of motion demonstration on video, we…can get most of the information, especially if we’ve already had one in-person visit with them.” Markova provides a guide on how to take good photos at home to assist with telemedicine visits.

Some patients are better candidates for telehealth than others. Markova cites some disease components, such as hair loss, that are challenging to examine without in-person visits. Harris said that pulmonary function tests can’t be done remotely, but if necessary, he can have them performed locally and the referring physician can send him the results.

Regarding rehabilitation assessments, Syrkin has been able to adapt some of the clinical metrics he uses for telehealth. He will request that a caregiver be present and the patient’s space be cleared of obstructions during a telehealth appointment so the camera can be positioned correctly and Syrkin can observe the patient’s gait in a safe environment where they can walk, turn, and move around comfortably.

TELEMEDICINE AT A CROSSROADS

A significant barrier facing the expansion of telehealth in the US is the state licensing requirements that prevent physicians from treating patients across state lines. Emergency waivers removed these requirements during the COVID-19 pandemic, but now they stand in the way of treating patients across state lines. According to the Federation of State Medical Boards, as of October 2024, only 21 states plus the District of Columbia allow permanent interstate telemedicine. There are many limitations on how it can be used.¹

Multidisciplinary clinics for rare diseases are not common nationwide and tend to be located in large cities, meaning that patients who live far away don’t have in-person access to specialized care for GVHD, Ponce pointed out. She and the others are advocates for New York and other states to waive licensing restrictions for telehealth for GVHD and other rare or orphan diseases.

In addition to the licensing limitations, many patients, particularly in pediatrics, are on supplemental or state health insurance, limiting access to care out of state. “I have a patient that could live only an hour away in New Jersey who I would not be able to see by telehealth because I’m not licensed in the state of New Jersey…who could…benefit from having access to a multidisciplinary team of people that have expertise in chronic GVHD,” said Harris. “These artificial barriers…that are put forth by state health care need to be revisited—whether they are in this patient’s best interest to limit their access to having specialized care for some of these very rare diseases that have a lot of severe implications for patient well-being, patient health, and patient survival.”

The clinic has been referred cases nationwide where telehealth would make treatment easier. Harris described a patient in Kansas City, Missouri, who would need to be healthy and stable enough to travel to New York to see the multidisciplinary team because the licensing restrictions prevent them from using telehealth.

“Ultimately, everybody wants patients to have access to good care, and sometimes that good care is not available for some of these very rare diseases in their backyard or even within their own state,” Harris said. “These are things that need to be revisited, addressed, and we have to come up with solutions for some of these rare and orphan diseases that currently aren’t in place.”

_REFERENCE

_{1. Comparison of states with permanent interstate telemedicine. Federation of State Medical Boards. Updated October 2024. Accessed November 5, 2024. https://www. fsmb.org/siteassets/advocacy/key-issues/comparison-of-states-with-permanent-interstate-telemedicine.pdf}