Corey S. Cutler, MD, MPH, FRCPC, medical director, Adult Stem Cell Transplantation Program, director of Clinical Research, Stem Cell Transplantation, director, Stem Cell Transplantation Survivorship Program, institute physician, Dana-Farber Cancer Institute, and associate professor of medicine, Harvard Medical School, discusses remaining challenges in graft-versus-host disease (GVHD).

Early identification of patients with GVHD who are unlikely to respond well to corticosteroids remains a clinical need, says Cutler. Additionally, understanding which patients require augmented therapy up front compared with those who can receive de-escalated treatment require more study.

While biomarkers for chronic GVHD are less developed, biomarkers for acute GVHD (aGVHD) could aid in identifying these patients, explains Cutler.

The randomized phase 2 BMT CTN 1501 trial showed that single-agent sirolimus (Rapamune) is a viable option for patients with standard-risk aGVHD and is associated with reduced steroid exposure, greater immune suppression discontinuation, and improved quality of life compared with prednisone, concludes Cutler.

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Corey S. Cutler, MD, MPH, FRCPC, discusses remaining challenges in graft-versus-host disease.

Dr. Cutler on Remaining Challenges in GVHD

Corey S. Cutler, MD, MPH, FRCPC, medical director of the Adult Stem Cell Transplantation Program; director of Clinical Research, Stem Cell Transplantation; director of the Stem Cell Transplantation Survivorship Program; and institute physician at Dana-Farber Cancer Institute; as well as an associate professor of medicine at Harvard Medical School, discusses some of the novel preventive strategies against graft-versus-host disease (GVHD).

A significant unmet need with regard to GVHD is prevention, says Cutler; however, ongoing research efforts are exploring novel preventive regimens. Specifically, investigators are developing ways to manipulate the stem cell graft, take out specific T-cell fractions, or modulate the graft to prevent GVHD, says Cutler.

Additionally, several post-transplant medical interventions are available. For example, the post-transplant cyclophosphamide regimen is growing in importance. Additionally, other immunosuppressive agents are available, such as abatacept (Orencia), which is a costimulatory blockade agent that can help prevent GVHD, concludes Cutler.

Corey S. Cutler, MD, MPH, FRCPC, discusses some of the novel preventive strategies against graft-versus-host disease.

Dr. Cutler on Novel Preventive Strategies Against GVHD

Corey S. Cutler, MD, MPH, FRCPC, medical director, Adult Stem Cell Transplantation Program, director of Clinical Research, Stem Cell Transplantation, director, Stem Cell Transplantation Survivorship Program, institute physician, Dana-Farber Cancer Institute, and associate professor of medicine, Harvard Medical School, discusses methods to optimize treatment for patients with acute and chronic graft-versus-host disease (GVHD).

Optimizing management of acute GVHD requires a lot of attention to supportive care measures that go along with the treatment of patients with severe acute GVHD, including bowel rest, total parenteral nutrition, or antibiotics for the prevention of infection, explains Cutler. Specialists in different departments can be consulted in the care of these patients. For example, colleagues working in dermatology or the burn unit can help with the management of patients with GVHD who are severely affected, and hepatology colleagues can help patients who have affected livers, suggests Cutler.

Patients with chronic GVHD have access to many more supportive care measures. Patients are offered local care of individually affected organs, such as topical care of the eye, mouth, skin, or the gastrointestinal tract, says Cutler. Addressing these local needs for chronic GVHD is just as important as the systemic therapies used to treat patients, concludes Cutler.

Corey S. Cutler, MD, MPH, FRCPC, discusses methods to optimize treatment for patients with acute and chronic graft-versus-host disease.

Dr. Cutler on Optimizing Treatment for Acute and Chronic GVHD

Corey S. Cutler, MD, MPH, FRCPC, medical director, Adult Stem Cell Transplantation Program, director of clinical research, Stem Cell Transplantation, director, Stem Cell Transplantation Survivorship Program, institute physician, Dana-Farber Cancer Institute, and associate professor of medicine, Harvard Medical School, discusses treatment options for patients with acute and chronic graft-versus-host disease (GVHD).

The standard treatment for patients who develop acute GVHD is corticosteroids. These drugs can induce a response rate of 50% to 75%, says Cutler.

In May 2019, the FDA approved ruxolitinib (Jakafi) for the treatment of adult and pediatric patients ≥12 years of age with steroid-refractory acute GVHD. The approval was based on data from the phase II REACH1 trial, in which ruxolitinib led to a 57% overall response rate (ORR). Other agents that may have utility after ruxolitinib are currently under investigation, explains Cutler.

Corticosteroids are the mainstay of treatment in chronic GVHD as well. However, 50% to 60% of patients with chronic GVHD become resistant to corticosteroids within the first year of therapy, says Cutler.

In those cases, ibrutinib (Imbruvica) can be considered. The BTK inhibitor was approved in August 2017 for the treatment of patients with chronic GVHD who progressed on ≥1 line of systemic therapy. The approval was based on data from the single-arm phase Ib/II PCYC-1129 trial, in which ibrutinib led to a 67% ORR.

There is no approved standard third-line therapy for patients with chronic GVHD, says Cutler. However, KD025, an experimental ROCK2 inhibitor, has shown encouraging data in this space. In the phase II ROCKstar trial (NCT03640481), KD025 led to a 64% ORR at a daily dose of 200mg in patients with chronic GVHD who received ≥2 prior systemic therapies.

Corey S. Cutler, MD, MPH, FRCPC, discusses treatment options for patients with acute and chronic graft-versus-host disease.



Corey S. Cutler, MD, MPH, FRCPC

Articles

Dr. Cutler on Remaining Challenges in GVHD

Dr. Cutler on Novel Preventive Strategies Against GVHD

Dr. Cutler on Optimizing Treatment for Acute and Chronic GVHD

Dr. Cutler on Treatment Options for Acute and Chronic GVHD