New Treatments Lend a Positive Outlook to Patients With GVHD


There are now more drugs than ever to treat and prevent graft-versus-host disease in patients with blood cancer who receive a stem cell transplant.

For many patients with blood cancers, an allogeneic stem cell transplant offers them the opportunity to potentially have their disease cured. However, the process comes with its own set of risks, too — mainly a condition called graft-versus-host disease (GVHD), where a patient’s body rejects and attacks the donor.

GVHD can be severe — or even fatal — though medical advancements in recent years have fine-tuned the way that it is treated, leading to better outcomes for patients with the condition, explained Dr. Scott D. Rowley, a professor of Medicine at Georgetown University School of Medicine in Washington.

“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,” Rowley said.

Rowley, who is also a hematologist oncologist at John Theurer Cancer Center in Hackensack, New Jersey, and Lombardi Comprehensive Cancer Center, recently discussed new and emerging treatments for GVHD at the 26th Annual International Congress on Hematologic Malignancies.

Treating Acute GVHD

Acute GVHD occurs when a patient develops GVHD within 100 days after their transplant. This December, the Food and Drug Administration (FDA) approved Orencia (abatacept) plus 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.

Orencia 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 (Orencia) 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 Jakafi (ruxolitinib). This approval was based on an open-label, phase 3 clinical trial that showed that Jakafi can treat chronic GVHD that was not responsive to steroids, which is typically the first line of treatment against the condition.

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

Chronic GVHD Treatment

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 Imbruvica (ibrutinib), which was given the OK by the FDA in 2017. Imbruvica works by inhibiting two components in the immune system: BTK signaling pathways and interleukin-2 T-cell kinase.

“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.

Jakafi is also approved for GVHD in the chronic, steroid-refractory state. “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.

Most recently, Rezurock (belumosudil) 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.

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 scary 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 blood cancers.

“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.

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