Emily Baumrin, MD, MSCE

Credit: Penn Medicine

Patient-reported outcomes (PROs) are significant measures of disease severity in patients with cutaneous chronic cutaneous chronic graft-vs-host disease (GVHD), according to recent findings, and they could function as a clinical prognostic marker for mortality.¹

These findings resulted from a new multicenter study assessing whether or not cutaneous chronic graft-vs-host disease has an independent link to patient-reported outcome impairment. The research was led by Emily Baumrin, MD, MSCE, from the department of dermatology at the University of Pennsylvania, Philadelphia.

Baumrin and colleagues noted that previous research had looked into the association of impairment of patient-reported outcomes with skin chronic GVHD, as well as GHVD’s possible connection to rates of mortality.²

“This multicenter prospective cohort study aims to juxtapose longitudinal PROs in patients with epidermal and sclerotic disease and assess whether PROs independently pinpoint individuals with elevated mortality risk,” Baumrin and colleagues wrote.

Background and Methods

The investigators utilized a multicenter, prospective cohort trial design. The Chronic GVHD Consortium, which had been formed between 2007 - 2012 in a total of 9 medical centers found in the US, was made up of individuals with chronic GVHD diagnoses who also required systemic immunosuppression.

The research team regularly evaluated cases of chronic GVHD activity, and data was later censored at the point of patient relapse or at resolution occuring over a year. The team then monitored up until December 2020 for death and instances of relapse.

The investigators’ research was aimed at adults aged 18 and above that also had chronic GVHD at the point in which they enrolled or at the time of the study period. The team implemented standardized forms which were based upon by the National Institutes of Health (NIH) response criteria for the purposes of defining skin involvement, and their criteria for subject exclusion encompassed individuals without involvement on skin or that had genital-only involvement.

The research team assessed the burden of patient-reported symptoms through the use of the Lee Symptom Scale (LSS) skin subscale, where scores shown to be higher would denote more more severe health outcomes.

The team also evaluated subjects’ quality of life by using the Functional Assessment of Cancer Therapy–Bone Marrow Transplantation (FACT-BMT) tool, in which scores shown to be lower would suggest worse outcomes. They also looked at rates of non-relapse death and overall survival, in addition to correlation with patient-reported outcomes by the point of the subjects’ diagnosis.

Findings

There were a total of 436 subjects that had cutaneous chronic GVHD, with 59.9% noted as being male and a median age at the point of their transplant being 51 years. The investigators found that 52.5% had epidermal-type chronic GVHD, 30.0% of them had sclerotic, and 17.4% of them had combination disease.

Once the research team adjusted for confounding variables, they found that subjects that had sclerotic chronic GVHD were shown to have a mean FACT-BMT score that was 6.1 points below that of subjects with epidermal disease (95% CI, 11.7-0.4; P = .04). The mean LSS skin subscale score of those with combination was found to be 9.0 points below that of individuals with epidermal disease (95% CI, 4.2-13.8; P < .001).

The investigators defined clinically meaningful differences as 7 points lower at minimum for FACT-BMT scores and 11 points higher for scores on the LSS skin subscale. A clinically meaningful lowering of score on the FACT-BMT assessment at the point of a patient’s diagnosis was shown by the team to be linked with a 9.1% rise in adjusted odds of non-relapse mortality (95% CI, 2.0%-16.7%; P = .01).

In a similar vein, the research team found that on the LSS score, a clinically meaningful score lowering led to an adjusted odds of non-relapse mortality rise of 16.4% (95% CI, 5.4%-28.5%; P = .003). Even after the team adjusted for clinical severity by the National Institutes of Health Skin Score, the link was proven to be substantial.

“The degree of impairment in PROs at skin chronic GVHD diagnosis was shown to be a prognostic marker for overall survival and nonrelapse mortality independent of clinical severity,” they wrote. “Future studies should focus on psychometric validation of PROs so that they can be incorporated as a prognostic and response marker in clinical practice and clinical trials.”

References

1. ^{Baumrin E, Shin DB, Mitra N, et al. Patient-Reported Outcomes and Mortality in Cutaneous Chronic Graft-vs-Host Disease. JAMA Dermatol. Published online February 28, 2024. doi:10.1001/jamadermatol.2023.6277.}
2. ^{Baumrin E, Baker LX, Byrne M, et al. Prognostic value of cutaneous disease severity estimates on survival outcomes in patients with chronic graft-vs-host disease. JAMA Dermatol. 2023;159(4):393-402. doi:10.1001/jamadermatol.2022.6624.}