Durable discontinuation of immunosuppressive therapy rare in chronic GVHD
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The majority of patients with chronic graft-versus-host disease are unable to discontinue immunosuppressive therapy for more than 1 year, according to retrospective study results presented at TCT Meetings Digital Experience.
Graft source, use of myeloablative conditioning, Lee symptom score, platelet count and lower gastrointestinal involvement all appeared to influence the likelihood of durable discontinuation.
“The low number of patients who could actually come off immunosuppressive therapy was surprising,” researcher George Chen, MD, associate professor of oncology at Roswell Park Comprehensive Cancer Center, told Healio. “It indicated that chronic GVHD is a long-term problem and not a temporary setback as previously thought.”
An estimated 30% to 70% of patients who undergo allogeneic HSCT and survive for more than 100 days will develop and require treatment for chronic GVHD.
Successful treatment often requires long-term systemic immunosuppressive therapy. However, this can impair immune function, putting patients at risk for infections and leading to medication-specific adverse effects, according to study background.
About half of patients who stop immunosuppressive therapy for the first time need to resume it after a median 3 months.
“There is a lack of data on how long it takes to taper off immunosuppressive therapy with which to counsel patients who develop chronic GVHD,” Chen said.
Prior studies that assessed immunosuppressive therapy discontinuation reported long-term discontinuation rates ranging from 27.7% to 68%. Population differences between studies may explain this wide range, Chen said. The definition of what constituted immunosuppressive therapy discontinuation also varied among studies, making it more challenging to interpret the results.
Chen and colleagues retrospectively analyzed the time to, incidence of and factors associated with durable immunosuppressive therapy discontinuation. They defined durable discontinuation as 12 months or longer to ensure patients truly were unlikely to flare and need to restart therapy.
Researchers used data from two prospective cohorts of the Chronic Graft-Versus-Host Disease Consortium, a group of academic medical centers, patient support organizations and other research entities.
The analysis included 684 patients (median age, 51.9 years; range, 18-78).
Donor types were HLA-matched unrelated (44.7%), HLA-matched related (37.6%) and other (18%). The most common transplant source was peripheral blood (89%), followed by bone marrow (6.6%) and cord blood (4.4%). Half of patients received nonmyeloablative conditioning. Most patients had moderate (51.2%) or severe (32.2%) chronic GVHD.
Median time from HSCT to diagnosis of chronic GVHD was 7.7 months (range, 1-141.3) and median time from chronic GVHD onset to study enrollment was 0.9 months (range, 0-12).
Median follow-up was 95.3 months (range, 11.3-181.5).
One-third (33%; 95% CI, 28-37) of study participants successfully discontinued immunosuppressive therapy for at least 12 months. Median time from cohort enrollment to immunosuppressive therapy discontinuation was 40.4 months (range, 8.6-142.7).
Multivariable analysis that controlled for clinical and patient-reported variables identified several factors associated with reduced likelihood of durable immunosuppressive therapy discontinuation. These included myeloablative conditioning (HR = 0.6; 95% CI, 0.45-0.85), platelet counts of 100,000/l or higher (HR = 0.59; 95% CI, 0.39-0.89), moderate or severe lower GI involvement (HR = 0.23; 95% CI, 0.06-0.93), and higher Lee symptom scores (HR = 0.98; 95% CI, 0.96-1).
Patients with mild lower GI involvement (HR = 1.71; 95% CI, 1.02-2.87) and those whose transplant source was cord blood (HR vs. peripheral blood = 2.07; 95% CI, 1.07-4.03) appeared more likely to attain durable immunosuppressive therapy discontinuation.
An analysis that included NIH chronic GVHD severity showed those with severe chronic GVHD were less likely to attain durable immunosuppressive therapy discontinuation (HR = 0.53; 95% CI, 0.31-0.9).
The findings suggest chronic GVHD may behave more like an ongoing immune disease that requires ongoing immune suppression rather than a temporary state where eventual tolerance is expected, Chen said. Taking this view toward chronic GVHD has implications for management approaches and therapeutic development, he added.
“Patients need to stay on immunosuppressive therapy as long as they need to get past chronic GVHD,” Chen told Healio. “Instead of constantly trying to reduce immunosuppression and possibly causing a flare of chronic GVHD, we should keep our patients on it. It might cause less morbidity overall in the end. ... Therefore, we should choose agents that have the least side effects that can be given long term over many years.”
Chen and colleagues acknowledged limitations of the study, including its retrospective nature and the fact immunosuppressive therapies were considered as a whole rather than individual drugs or classes of therapies.
“Being able to do so might have revealed which drugs or classes of drugs are more effective for treating chronic GVHD,” Chen said.
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Chen GL, et al. Abstract 8. Presented at: The 2021 TCT Meetings Digital Experience (virtual meeting); Feb. 8-12, 2021.
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