Association of treatment-sensitive, dependent, and resistant chronic GvHD with clinical outcomes

Immunosuppressive therapy (IST) is frequently used to treat patients who develop chronic graft-versus-host disease (cGvHD) following allogeneic hematopoietic stem cell transplantation. However, patients can become treatment-resistant, sensitive, or dependent resulting in increased morbidity, poorer overall survival (OS), and difficulties in tapering off treatment.

Here, we summarize an article by Jurdi et al.¹ published in Transplantation and Cellular Therapy evaluating the association of treatment-sensitive (TS), treatment-dependent (TD), and treatment-resistant (TR) cGvHD on clinical outcomes.

Study design¹

• This was a retrospective, single-center study of adult and pediatric patients who developed cGvHD after receiving allogeneic hematopoietic stem cell transplantation.
• Eligible patients were either TR, TS, or TD to systemic corticosteroids or IST.
• Clinical outcomes measured included failure-free survival, disease-free survival, OS, and non-relapse mortality.

Key findings¹

• In total, 185 patients received systemic therapy within 30 days of cGvHD onset.
  • 126 patients achieved durable discontinuation of IST (within a median time of 18 months).
• The median follow-up, after cGvHD onset, was 7 years.
• Patients with cGvHD stratified by treatment responses are shown in Table 1.

Table 1. Treatment response group classifications after cGvHD onset*

	TS (n = 24)	TD (n = 51)	TR (n = 85)	Deceased
6 months (%)	5	46	41	8
1-year (%)	13	27	46	14
2-years (%)	29	5	44	22
cGvHD, chronic graft-versus-host disease; TD, treatment-dependent; TR, treatment-resistant; TS, treatment-sensitive. *Data from Jurdi, et al.1

• Examination of the association of treatment response group and clinical factors indicated that patients with older age, prior acute GvHD, or severe cGvHD were more likely to be TD or TR at 1 or 2 years post-cGvHD onset.
• Using treatment responses at 1-year post-cGvHD diagnosis, cumulative incidence estimates of 5-year clinical outcomes across the treatment response groups were determined (Figure 1).

cGvHD, chronic graft-versus-host disease; DFS, disease-free survival; FFS, failure-free survival; NRM, non-relapse mortality; OS, overall survival; TD, treatment-dependent; TR, treatment-resistant; TS, treatment-sensitive.
*Data from Jurdi, et al.¹

• In a multivariable model of the risk of death from 1–5 years after cGvHD, the adjusted hazard ratio for 1-year response in patients who were TR vs TS was 1.08 (95% confidence interval, 0.41–2.87).
• In a separate analysis comparing patients with no history of cGvHD, TR cGvHD was associated with poor OS at 5 years (hazard ratio, 2.09; p < 0.01).

Key learnings
Refining cGvHD classifications into treatment response groups (TS, TD, and TR) can be a useful predictor of early and late clinical outcomes, thus helping to better identify patients who need more effective treatments. The analysis highlights the importance of long-term follow-up to determine treatment sensitivity in patients receiving chronic GvHD treatment.