Success of Immunosuppressive Treatments in Patients with Chronic Graft-versus-Host Disease

Abstract

Moderate to severe chronic graft-versus-host disease (GVHD) is treated with potent immunosuppressive therapy (IST) to modulate the allo-immune response, control symptoms, and prevent further organ damage. We sought to understand the types of treatments used in clinical practice and the likelihood of successful treatment associated with each. A chart review was performed for 250 adult patients at Fred Hutchinson Cancer Research Center enrolled in a prospective observational study. After a median follow-up of 5.6 years for survivors, approximately one-third were still on IST (of whom half were on fourth or greater line of therapy), one-third were alive and off IST, and one-third had relapsed or died. Approximately half of survivors stopped all IST at least once, although half of these restarted IST after a median of 3.4 months (interquartile range, 2.3 to 8.0) off therapy. Successful discontinuation of IST for at least 9 months was associated with myeloablative conditioning (P = .04), more years since transplant (P = .009), and lack of oral (P < .001) and skin (P = .049) involvement compared with those who had to restart IST. We conclude that patients with chronic GVHD usually receive multiple lines and years of IST, with only a third off IST, alive, and free of malignancy at 5 years after chronic GVHD diagnosis. Patients stopping IST should be cautioned to self-monitor and continue close medical follow-up, especially for 3 to 6 months after stopping IST.

Evolving Therapeutic Options for Chronic Graft‐versus‐Host Disease

“…However, each attempt to taper risks subsequent flare of GVHD and the need to restart IST at potentially higher dosages. 95 Prolonged need for IST was previously noted in certain cGVHD manifestations. 93 However, more recent data have emerged regarding this important outcome.…”

“…Previously reported median duration of IST post-HCT is~2 years in patients receiving BM grafts and 3.5 years with PBSC grafts. [93][94][95] Overall, 50% of cGVHD patients may require additional secondline therapies. No specific agent has shown significant benefit over another, and responses are highly variable ranging from 20-70%.…”

How I treat refractory chronic graft-versus-host disease

“…Recent natural history data from the cGVHD consortium affirm that patients who have a flare of cGVHD on first wean of immunosuppression are highly likely to remain on therapy, and subsequent tapers of agents are associated with reflares. 10,12,24,83 When cGVHD flares during immunosuppression wean, readministration of steroids commonly occurs, especially with manifestations involving lifesustaining organs. Data are lacking regarding when and whether to reinstitute steroids or whether other agents would benefit patients.…”

Challenges in Conducting Studies in Chronic Graft-versus-Host Disease

“…cGvHD relapse-free survival (CRFS) is defined as freedom from the development of cGvHD, relapse, or death at 12 months. A recent study by Lee et al showed that for patients with cGvHD who start initial systemic immunosuppression, there is only a 32% chance that they will be alive, in remission, and off immunosuppression (e.g., ISRS) 5 years after cGvHD diagnosis [66]. Use of these composite endpoints in prevention trials could increase the precision of outcome analysis in regard to GvHD, relapse, and survival.…”