Recent Approvals Show Shift in SOC for Graft-Versus-Host Disease


The treatment and preventive agent landscape for graft-versus-host disease is growing for patients with hematologic malignancies who receive a stem cell transplant.

Scott D. Rowley, MD

Scott D. Rowley, MD

In the treatment of hematologic malignancies, an allogeneic stem cell transplant (ASCT) offers oncologists to achieve disease remission in their patients. However, the process comes with its own set of risks — mainly graft-versus-host disease (GVHD.1

“Allogeneic transplant is known to have a very potent graft-versus-tumor effect with the idea that this immunological response can lead to cure of an underlying hematological disease. But we do have our complications,” said Scott D. Rowley, MD, a professor of Medicine at Georgetown University School of Medicine.

Rowley, who is also a hematologist oncologist at John Theurer Cancer Center, and Lombardi Comprehensive Cancer Center, recently discussed new and emerging treatments for GVHD at the 226th Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas, and Myeloma.

Managing Acute GVHD

In December 2021, the FDA granted approval to abatacept (Orencia) in combination with another immunosuppressive drug to prevent acute GVHD in children (aged 2 or older) or adults who underwent a hematopoietic stem cell transplant from an unrelated donor.2

Abatacept works by inhibiting T-cell activation and B-cell immunological response — two processes that contribute to the body’s response against donor cells.

“[Researchers] found that adding [abatacept] greatly reduced the risk of severe graft-versus-host disease. What’s more interesting is that at 180 days out, even with a mismatch [donor], there was a very high degree of preventing severe, acute GVHD,” Rowley explained.

Also approved for acute GVHD is ruxolitinib (Jakafi). This approval was based on an open-label, phase 3 clinical trial (Study INCB 18424-271, NCT02953678), which showed that ruxolitinib can treat chronic GVHD that was not responsive to steroids, which is typically the first line of treatment against the condition.3

“There was a higher [complete response] rate with the addition of [ruxolitinib] and then maintaining the acute GVHD-free survival,” Rowley said.

Chronic GVHD Management

When a patient experiences GVHD after 100 or more days from treatment, it is called chronic GVHD. Again, steroids are typically the go-to response for chronic GVHD, but if they do not work, there are FDA-approved regimens for this patient population as well.

The first drug to be granted FDA approval for chronic, steroid-refractory GVHD was ibrutinib (Imbruvica) , which was approved by the FDA in 2017. Ibrutinib works by inhibiting 2 components in the immune system: Bruton’s tyrosine kinase signaling pathways and interleukin-2 T-cell kinase.4

“There’s a small proportion of patients who actually get a complete response of their chronic GVHD, but it was effective across the board. So, it wasn’t effective just for skin or mouth or GI-related GVHD. And it was effective for patients who had more severe chronic GVHD that involved more than one organ,” Rowley said.

Ruxolitinib is also approved for GVHD in the chronic, steroid-refractory phase. “Again, the responses were sustained, and (Jakafi) has become one of our major players in the management of chronic GVHD in our centers,” Rowley said.5

Most recently, belumosudil (Rezurock) was granted FDA approval for individuals aged 12 and over who have chronic GVHD and have received at least two lines of prior therapy. This drug inhibits ROCK signaling, which is a key player in the coordination of T-cell mediated immune response.6

On the phase 2 clinical trial that led to the approval, 20% of patients were able to stop steroid treatment, and many saw that their GVHD symptoms improved, too.

Ultimately, while GVHD can be a complication from stem cell transplant, clinicians have more tools than ever to treat and prevent the condition, leading to better outcomes overall for patients with hematologic malignancies.

“We now have a choice of conditioning regimens and donor selections. We can wave a matrix together or how we’re going to approach this particular patient,” Rowley said.


1. Rowley S. New and Emerging Standards of Care for GVHD. Presented at: 2022 International Congress on Hematologic Malignancies: Focus on Leukemias, Lymphomas, and Myeloma; February 23-25, 2022; Miami, FL.

2. FDA approves abatacept for prophylaxis of acute graft versus host disease. News release. FDA. December 15, 2021. Accessed February 28, 2022.

3 . FDA approves ruxolitinib for acute graft-versus-host disease. News release. FDA. May 24, 2019. Accessed February 28, 2022.

4. U.S. FDA approves Imbruvica® (ibrutinib) as first approved treatment specifically for adults with chronic graft-versus-host-disease (cGVHD) -- A serious, potentially life-threatening condition -- after failure of one or more lines of systemic therapy. News release. AbbVie. August 2, 2017. Accessed February 28, 2022.

5. FDA approves ruxolitinib for chronic graft-versus-host disease. News release. FDA. September 22, 2021. Accessed February 28, 2022.

6. FDA approves belumosudil for chronic graft-versus-host disease. News release. FDA. July 16, 2021.

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