Researchers from the University of Minnesota and Michigan have reported that the administration of Kepivance (palifermin, keritinocyte growth factor) before and after allogeneic stem cell transplantation reduces the incidence and mean severity of mucositis in patients receiving a total body irradiation (TBI) conditioning regimen. The details of this study appeared in the November 1, 2006, issue of Blood.

Oral mucositis is a frequent clinical problem in patients receiving chemotherapy and/or radiation therapy. Mucositis can be a severe dose-limiting toxicity, especially in patients receiving autologous or allogeneic stem cell transplants or radiation therapy for head and neck cancers. Although many specific and non-specific prophylactic and therapeutic treatments have been evaluated, there was no proven therapy for the prevention or treatment of mucositis prior to the FDA approval of Kepivance. However, the data for approval of Kepivance was generated in patients receiving autologous stem cell transplantation and, until the present report, no data were available in the allogeneic stem cell transplant setting.

Preclinical studies of allogeneic stem cell transplantation in rodent models have suggested that Kepivance may have a preventative effect on the development of acute GVHD. These observations led to the current trial which was designed primarily to determine if Kepivance would have a positive impact on the development of acute GVHD. In this study, 100 patients with hematologic malignancies received allogeneic stem cell transplants following a cyclophosphamide and TBI regimen or following a busulfan and cyclophosphamide regimen. GVHD prophylaxis was with 4 doses of methotrexate and cyclosporine or tacrolimus. Sixty-one patients were allocated to the Kepivance arm and 31 to the control arm.

These researchers reported that Kepivance had no impact on the incidence or severity of acute GVHD, hematopoietic recovery, relapse or survival. However, they observed a decreased incidence and mean severity of mucositis in patients conditioned with a cyclophosphamide-TBI regimen but not in those conditioned with a regimen of busulfan and cyclophosphamide. These authors concluded that Kepivance was safe to administer in recipients of allogeneic stem cell transplants and had a positive impact on patients treated with a TBI-based regimen associated with severe mucositis.

Comments: This is the first study of Kepivance in allogeneic stem cell transplant recipients. The study was designed to determine whether or not Kepivance had an effect on acute GVHD. Although this study did not show an effect in patients receiving methotrexate and cyclosporine there will undoubtedly be other studies in patients receiving different GVHD prophylactic regimens. This study showed that Kepivance decreased the incidence and severity of mucositis following a TBI conditioning regimen, which confirmed previous observations in the autologous stem transplant setting.

Reference: Blazar BR, Weisdorf DJ, Todd deFor, et al. Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Blood 2006;108:3216-3222.

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