Review: Treatment Options Expanding in GVHD After HSCT, but More Data Needed

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A new review article highlights some of the newest therapies available to treat graft-versus-host disease (GVHD), but the authors say there is insufficient data to draw broad conclusions.

Patients with diseases of the hematopoietic system can benefit from allogeneic hematopoietic stem cell transplantation (alloHSCT), but a significant proportion will experience graft-versus-host disease (GvHD).

In a new review article in Clinical Drug Investigation, corresponding author Deborah S. Hooker, PhD, an independent market access consultant, and colleagues argue that despite the availability of new treatment options, more work needs to be done to help physicians devise the best strategies for individual patients.

Hooker and colleagues began by explaining why allo-HSCT is becoming a more common therapeutic option for patients with diseases of the hematopoietic system.

“Several advances in alloHSCT procedures, including better tolerated and safer transplantation therapies have allowed more patients to reach complete disease response, with a lower patient burden,” they said. “Subsequently, more patients have become eligible for alloHSCT, which has expanded access and also led to a reduction in transplant-related morbidity and mortality, as well as improved outcomes.”

Yet, the complex nature of the procedure means it requires a high level of expertise from the providers associated with the procedure. It also comes with a high price, upwards of $300,000 by day 100, Hooker and colleagues wrote.

Though the transplant itself is costly and complicated, many patients who receive the therapy will encounter difficulties post-transplant.

“Between 39% and 59% of alloHSCT patients will develop [acute] GvHD and around 36–37% will develop [chronic] GvHD,” the investigators wrote.

These GvHD instances come despite the use of prophylaxis, and bring with them significant additional financial burden. For instance, steroid-resistant chronic GvHD can double the health care costs of patients, the authors noted.

Hooker and colleagues outlined a number of current and potential treatments. For patients with grade I acute GvHD, topical steroids are typically used, as the disease merely involves the skin. For higher grades of acute GvHD, high-dose systemic steroids are typically used.

“However, the likelihood of steroid response decreases with increasing aGvHD severity, with around a third to half of patients becoming steroid-resistant and having a poor prognosis,” the authors wrote.


For chronic GvHD, first-line treatment is typically steroids with or without a calcineurin inhibitor (CNI).

“For physicians treating GvHD, the key aim is to balance the need for immunosuppression in order to control the GvHD, whilst maintaining a degree of immunocompetence against infection,” Hooker and colleagues wrote.

A wide range of second-line therapies are recommended for GvHD, yet the authors said there is no accepted standard treatment for patients with steroid-refractory acute GvHD, meaning treatment decisions generally are based on physician experience. The authors said the wide range of treatments left them unable to recommend a standard second-line therapy for GvHD.

“The best recommendation the group could offer for second-line treatment of GvHD was that physicians should follow their institutional guidelines and patients should be treated within clinical trials when possible,” they wrote.

However, the investigators said newer therapies are becoming available that could significantly shift second-line options. Among the promising drugs recently approved are ibrutinib (Imbruvica) for steroid-resistant chronic GvHD, ruxolitinib (Jakafi) for steroid-refractory acute GvHD, and belumosudil (Rezurock) for patients with chronic GvHD that has failed to improve with 2 prior lines of systemic therapy.

In their conclusion, Hooker and colleagues said more research will be needed to elucidate the most effective therapies, the best methods for personalizing treatment, and the most cost-effective options.

“Improving and expanding the evidence base should be a priority for those investigating new therapeutic agents to challenge the current standards of care,” they wrote.


Hooker DS, Grabe-Heyne K, Henne C, Bader P, Toumi M, Furniss SJ. Improved therapeutic approaches are needed to manage graft-versus-host disease. Clin Drug Investig. Published online October 16, 2021. doi:10.1007/s40261-021-01087-6