Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.
In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.
This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”
Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.
Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.
Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.
Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.
Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.
Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.
“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.
The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).
Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).
In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.
“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”
The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.
This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.
SOURCE: Baker L. SID 2020, Abstract 434.