Rituximab May Reduce Chronic GVDH After Stem Cell Transplantation

Zosia Chustecka

December 09, 2010

December 9, 2010 (Orlando, Florida) — About half of the patients (50% to 60%) who receive an allogeneic stem cell transplant as treatment for leukemia or lymphoma develop the complication of graft-versus-host disease (GVHD), which can be life-threatening.

Current attempts to reduce the development of GVHD in such patients include immunosuppressants and T cell depletion (the complication has been considered to be a T cell–mediated disorder). However, recent data point to an overlapping pathophysiology and the involvement of B cells.

A new approach focuses on prophylactic rituximab, which depletes B cells. Early results from a single-group trial, presented here at the American Society of Hematology (ASH) 52nd Annual Meeting, show an incidence of chronic GVHD that is lower than that seen in historic controls and, in patients who do develop the complication, a reduction in steroid use of at least 50%.

Dr. Joseph Antin

"Improvements in transplantation tend to be incremental, and this is a good example of that," said Armand Keating, MD, vice president of ASH and professor of medicine at the University of Toronto in Ontario, where he holds the Epstein Chair in Cell Therapy and Transplantation.

"These results provide a strong rationale for conducting a prospective phase 3 study," Dr. Keating noted.

Coauthor of the study, Joseph Antin, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, agreed. "These results provide scaffolding on which to hang a randomized trial; they provide the statistical framework," he told Medscape Medical News.

Dr. Antin presented the results at an ASH press briefing that was moderated by Dr. Keating, although the presentation at the meeting itself was made by first author Corey Cutler, MD, also from the Dana-Farber Cancer Institute.

Preventing Chronic Complications

GVHD develops because of genetic differences between the donor and the recipient, Dr. Antin explained. The donor cells recognize the recipient cells as foreign and launch an immune attack, which results in debilitating symptoms that include skin rashes, blisters, joint pain, stiffness, dry mouth, and dry eyes. This reduces quality of life, and it can become life-threatening, he added.

There are 2 phases of GVHD — acute and chronic, Dr. Antin explained. This study set out to prevent the development of chronic GVDH with prophylactic rituximab.

It was conducted in 64 patients who were in remission after allogeneic stem cell transplantation as treatment for acute myeloid leukemia (n = 25), non-Hodgkin's or Hodgkin's lymphoma (n = 18), myelodysplastic syndrome (n = 10), or other leukemias (n = 5). Median age was 55 years (range, 19 to 74).

Primary GVHD prophylaxis was sirolimus plus tacrolimus (in 67.0% of patients) or a calcineurin inhibitor plus methotrexate (32.1%)

In addition, rituximab (375 mg/m2) was administered at 3, 6, 9, and 12 months after transplantation. One patient had a hypersensitivity reaction and the drug was discontinued, and 1 was lost to follow-up, leaving 54 evaluable patients.

The cumulative incidence of any chronic GVDH 1 year after stem cell transplantation was 44.6%. "This is substantially lower than has been seen historically," Dr. Antin noted.

The cumulative incidence of chronic GVDH that required treatment with steroids was only 31.2%; historically, nearly 100% required steroids, he said.

At 12 months, 50% of the patients had successfully discontinued all immunosuppressants and only 22.4% were receiving corticosteroids. Relapse-free survival was 71.1% and overall survival was 88.6%, which is "quite good," Dr. Antin said.

"Results of this study indicate that rituximab is a promising therapy for the prevention of chronic graft-versus-host disease following an allogeneic stem cell transplant," Dr. Corey concluded. They suggest that the drug could reduce steroid use by more half, he added.

The study was supported by various grants, including one from the National Cancer Institute. Rituximab for the study was provided by the manufacturer, Genentech/Roche.

American Society of Hematology (ASH) 52nd Annual Meeting: Abstract 214. Presented December 6, 2010.

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