ORLANDO — Rituximab prophylaxis can help to reduce the incidence of chronic, steroid-requiring graft-vs.-host disease in patients who undergo allogeneic stem cell transplants, investigators suggested at the annual meeting of the American Society of Hematology.
Dr. Joseph Antin
The 1-year cumulative incidence of chronic graft-vs.-host disease (GVHD) among 64 allogeneic stem cell recipients who received prophylactic rituximab (Rituxan) was about 40%, compared with about 65% for historical controls, reported Dr. Joseph Antin, chief of the stem cell transplantation program at the Dana-Farber Cancer Institute in Boston.
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In addition, only about one-third of rituximab-treated patients required steroids to control chronic GVHD when it developed, compared with nearly 100% of historical controls, Dr. Antin said at a media briefing.
Results of the ongoing study suggest that the strategy of B-cell depletion with rituximab may be effective at preventing or controlling GVHD, a condition once believed to be principally T-cell mediated. "B cells actually have substantial overlapping activities with T cells. In addition to their ability to produce antibodies, they can function as antigen-presenting cells, they can produce cytokines, and they have immunoregulatory characteristics," Dr. Antin said.
The investigators had previously studied the use of rituximab in patients with active chronic GVHD, and found that patients had a "reasonable" but unsustained response rate, he noted.
They presented data on 58 evaluable patients out of 64 enrolled to date. Patients who were at least 3 months out from an allogeneic stem cell transplant and had either recovered from any degree of acute GVHD or had never developed it were given a prophylactic dose of rituximab 375 mg/m2 (the standard dosage used in lymphoma therapy) at study entry and at months 6, 9, and 12. The patients underwent immunologic assessments at the time of each dose, and at 18 and 24 months. The patients were also assessed for clinical signs of GVHD at 6, 9, 12, and 24 months.
Overall, 25 patients (median age, 55 years) underwent transplants for acute myeloid leukemia, 18 for Hodgkin’s or non-Hodgkin’s lymphoma, 10 for myelodysplasia or myeloproliferative disorders, 3 for acute lymphoblastic leukemia, and 2 for chronic lymphocytic leukemia or promylocytic leukemia.
In 33 cases, the donors were HLA matched but unrelated to the recipient; in the remaining 25 the donors were related matches.
"We were concerned about the potential toxicity of giving a B-cell antibody at the time of [immunologic] recovery. Much of the morbidity of transplantation involves opportunistic infections that are intrinsic to the immunoincompetence of patients as they have gone through this procedure. In addition to that, rituximab used after autologous transplantation can result in cytopenia, which we were concerned about," Dr. Antin said.
There were 11 severe adverse events: 4 infectious (sepsis, febrile neutropenia, and pneumonia), 5 respiratory (pneumonitis, dyspnea, and hypoxia), 1 thrombotic microangiopathy, and 1 prolonged pancytopenia.
The 1-year cumulative incidence of steroid-requiring GVHD was 28.1%, compared with close to 100% of historical controls, he noted. Most of the cases of GVHD that did occur were not serious, manifesting primarily as oral and ocular symptoms that were amenable to topical therapy.
The 2-year overall survival rate is currently greater than 70%, and there is little evidence to suggest that chronic GVHD might be contributing to mortality, Dr. Antin said.
"The one concern we have is that chronic GVHD is associated with a graft-vs.-leukemia effect, and anything that abrogates graft-vs.-host disease has the potential of increasing the relapse rate, and that’s something that we need to continue to follow," he said.
Lead author Dr. Corey Cutler of Harvard Medical School in Boston presented the data in session. The study is supported by Genentech, Gateway for Cancer Research, and the Stem Cell Cyclists of the Pan-Mass Challenge. None of the authors had relevant conflict of interest disclosures.