Introduction
(Article introduction authored by Conquest Editorial Team)
Chronic graft-versus-host disease (GvHD) treatment response is assessed using NIH Consensus Criteria in clinical trials and clinician assessment in routine practice. Patient-reported response is essential for understanding chronic GvHD manifestations, treatment benefit, and toxicity but hasn’t been extensively studied.
We aimed to characterize 6-month patient-reported response, associated chronic GvHD features, and evaluate correlation with clinician/NIH responses. 382 subjects from two national studies were analyzed. At six months, 71% perceived improvement, with limited correlation to clinician or NIH responses.
Patient-reported response correlated with subsequent survival and certain NIH responses. Incorporating patient-reported responses in chronic GvHD trials and treatment development is recommended.
Methods
Patients were enrolled in two multicenter observational studies conducted by the Chronic GVHD Consortium. The first study, “Chronic GVHD Consortium Improvement Outcomes Assessment in Chronic GVHD,” enrolled 601 patients between 2007 and 2012, while the second study, “Chronic GVHD
Consortium Response Measures Validation Study,” enrolled 383 patients with chronic GvHD between 2013 and 2017. Both studies collected standardized information regarding chronic GvHD organ involvement and symptoms using forms developed according to NIH Consensus Criteria.
Exclusion criteria included primary disease relapse and inability to comply with study procedures. Patient-reported responses were categorized as “improved” or “not improved” based on an 8-point scale.
Statistical analysis included comparisons of characteristics and multivariable logistic regression to examine relationships between patient perception of chronic GvHD improvement and various factors. Survival analyses were conducted using the log-rank test.
Results
This study focused on 382 patients from a larger cohort who had baseline and 6-month patient-reported response data. The excluded 223 patients lacked 6-month response data mostly due to missed visits or surveys.
At baseline, patients had moderate to severe chronic GvHD, with skin, mouth, and eyes being the most commonly involved organ sites. At six months, 71% reported improvement, while 29% reported no improvement. Limited correlation was found between patient-reported response and clinician-reported or NIH response.
Multivariable analysis revealed associations between patient-reportedresponseandfactorssuchaslunginvolvement at enrollment and NIH responses in specific organ sites. Further analysis explored the relationship between patient perception of chronic GvHD improvement and quality of life/symptom burden measures.
Factors such as higher SF-36 general health score at enrollment and improvement in SF-36 general health score from enrollment to six months were associated with patient-reported improvement, while worsening in SF-36 role physical domain score was associated with no improvement.
Similar associations were observed with Lee Symptom Scale scores. Failure-free survival after six months was higher among patients reporting improvement, with the most common cause of failure being the initiation of new treatment for chronic GvHD. However, there was no significant difference in overall survival at six months between the groups.
Discussion
This study sheds light on patient-reported treatment response in chronic GvHD, an area that has been underexplored. The six-month patient-reported response was linked with subsequent failure-free survival (FFS), suggesting it could serve as a clinically meaningful measure. Notably, patient-reported response showed limited correlation with NIH and clinician-assessed responses, indicating its potential to capture unique aspects of clinical benefit.
Baseline chronic GvHD organ involvement, as well as organ responses, were found to be associated with patient-reported response, highlighting the importance of considering specific organ manifestations in assessing treatment outcomes, (Fig 1 and Fig 2)
While this analysis provides valuable insights, further research in larger patient populations is warranted for validation and refinement of conclusions regarding specific organ manifestations. Once validated, patient-reported response could be incorporated into clinical trials as a secondary outcome measure, complementing NIH responses.
Additionally, implementing a structured patient-reported ordinal response scale in routine clinical care could enhance the assessment of treatment benefit beyond traditional measures.
Despite some limitations, including retrospective analysis and heterogeneity in patient populations, the study underscores the significance of patient-reported responses in evaluating treatment efficacy and should be considered in future research and clinical practice in chronic GvHD therapy.
References
1. Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9(4):215-233. [PubMed] [Google Scholar]
2. Arai S, Arora M, Wang T, et al.. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2015;21(2):266-274. [PMC free article] [PubMed] [Google Scholar]
3. Martin PJ, Weisdorf D, Przepiorka D, et al.. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical Trials Working Group report. Biol Blood Marrow Transplant. 2006;12(5):491-505. [PubMed] [Google Scholar]
4. Filipovich AH, Weisdorf D, Pavletic S, et al.. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945-956. [PubMed] [Google Scholar]
5. Pavletic SZ, Martin P, Lee SJ, et al.. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant. 2006;12(3):252-266. [PubMed] [Google Scholar]
6. Lee SJ, Wolff D, Kitko C, et al.. Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. The 2014 Response Criteria Working Group report. Biol Blood Marrow Transplant. 2015;21(6):984-999. [PMC free article] [PubMed] [Google Scholar]
7. Jagasia MH, Greinix HT, Arora M, et al.. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401. [PMC free article] [PubMed] [Google Scholar]
8. Palmer J, Chai X, Pidala J, et al.. Predictors of survival, nonrelapse mortality, and failure-free survival in patients treated for chronic graft-versus-host disease. Blood. 2016;127(1):160-166. [PMC free article] [PubMed] [Google Scholar]
9. Martin PJ, Storer BE, Palmer J, et al.. Organ changes associated with provider-assessed responses in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2019;25(9):1869-1874. [PMC free article] [PubMed] [Google Scholar]
10. Palmer JM, Lee SJ, Chai X, et al.. Poor agreement between clinician response ratings and calculated response measures in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2012;18(11):1649-1655. [PMC free article] [PubMed] [Google Scholar]
11. Inamoto Y, Martin PJ, Chai X, et al.. Clinical benefit of response in chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2012;18(10):1517-1524. [PMC free article] [PubMed] [Google Scholar]
12. Pidala J, Kurland B, Chai X, et al.. Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium. Blood. 2011;117(17):4651-4657. [PMC free article] [PubMed] [Google Scholar]
13. Chronic GC. Rationale and design of the chronic GVHD cohort study: improving outcomes assessment in chronic GVHD. Biol Blood Marrow Transplant. 2011;17(8):1114-1120. [PMC free article] [PubMed] [Google Scholar]
14. Lee SJ, Hamilton BK, Pidala J, et al.; The Chronic GVHD Consortium. Design and patient characteristics of the Chronic Graft-versus-Host Disease Response Measures Validation Study. Biol Blood Marrow Transplant. 2018;24(8):1727-1732. [PMC free article] [PubMed] [Google Scholar]
15. Lee S, Cook EF, Soiffer R, Antin JH. Development and validation of a scale to measure symptoms of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8(8):444-452. [PubMed] [Google Scholar]
16. Inamoto Y, Flowers ME, Sandmaier BM, et al.. Failure-free survival after initial systemic treatment of chronic graft-versus-host disease. Blood. 2014;124(8):1363-1371. [PMC free article] [PubMed] [Google Scholar]
17. Inamoto Y, Storer BE, Lee SJ, et al.. Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease. Blood. 2013;121(12):2340-2346. [PMC free article] [PubMed] [Google Scholar]
