The use of patient-reported outcomes as a prognostic marker in cutaneous cGvHD

Most patients with chronic graft-versus-host disease (cGvHD) encounter skin involvement at some level (epidermal or sclerotic-type disease), with many also experiencing refractoriness to treatment.¹ Hence, there is a need to develop an effective method for identifying patients who are at a greater risk of mortality. The use of patient-reported outcomes (PROs) as a clinical prognostic marker, for initial risk stratification and treatment selection of cutaneous cGvHD, has not yet been established.¹

Here, we summarize an article by Baumrin et al.¹ published in JAMA Dermatology on the association of PROs and mortality in patients with cGvHD who experience skin involvement.

Study design¹

• The study used the Chronic GvHD Consortium, a longitudinal cohort from nine medical centers across the United States, consisting of patients who were diagnosed with cGvHD requiring systemic immunosuppression between 2007–2012.
• Patients with cGvHD and skin involvement during the study period were included. Skin involvement was defined into three categories (epidermal, sclerotic, and combination cutaneous cGvHD subtypes) using standardized forms, based on the 2005 National Institute of Health response criteria.
• The Lee Symptom Scale (LSS) skin subscale, consisting of a linear scale of 0–100, where a higher score indicates worse outcomes, was used to assess symptom burden.

• The Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) instrument version 4.0, which measures outcomes of cancer therapy using a scale of 0–148, with lower scores indicating worse outcomes, was used to assess quality of life.
• Mortality was assessed as overall survival (OS, time from skin cGvHD diagnosis to all-cause mortality) and non-relapse mortality (NRM, time from skin cGvHD diagnosis to death with relapse as a competing risk).

Key findings¹

• In total, 436 patients with cutaneous cGvHD (epidermal, n = 229; sclerotic, n = 131; and combination, n = 76) were included in this study.
• Throughout the study period, after adjusting for confounders, FACT-BMT scores and LSS skin subscale scores remained significantly worse for patients with sclerotic and combination disease compared with those with epidermal disease.
  • Patients in the sclerotic disease cohort displayed mean FACT-BMT scores which were 6.1 points worse than those with epidermal disease (95% confidence interval [CI], 11.7–0.4; p = 0.04).
• At skin GvHD diagnosis, a 7-point worsening in FACT-BMT score (clinically meaningful difference) was associated with a 9.1% (95% CI, 2.0–16.7%; p = 0.01) increase in the odds of NRM and a 9.1% (95% CI, 3.2–15.2%; p = 0.002) increase in the odds of mortality from any cause.
  • According to multivariable cumulative hazard functions, patients with the lowest tertile of FACT-BMT scores at skin GvHD diagnosis had lower OS (p = 0.005) and higher NRM (p = 0.03).
• A clinically meaningful worsening in LSS skin subscale points (11-point increase) was associated with a 16.4% (95% CI, 5.4–28.5%; p = 0.003) increase in the odds of NRM and a 10.0% (95% CI, 1.2–19.5%; p = 0.02) increase in the odds of mortality from any cause.
  • According to multivariable cumulative hazard functions, patients with the highest tertile of LSS skin subscale scores at diagnosis had lower OS (p = 0.10) and higher NRM (p = 0.02).

Key learnings

In this cohort study, patients with sclerotic and combination-type skin cGvHD exhibited the highest persistent impairment in PROs. The severity of impairment in PROs at the time of skin cGvHD diagnosis was shown to be a prognostic marker for NRM and OS. Following further validation, evaluation of PROs may aid healthcare professionals with treatment selection and risk stratification for patients with skin GvHD.