There were several clinical studies presented at the 2006 meeting of the American Society of Hematology in December which suggest that Kepivance (palifermin) is effective in decreasing the incidence, severity and duration of severe oral mucositis in patients with hematologic diseases receiving high-dose Alkeran® (melphalan) (200 mg/m2) or high-dose BEAM (carmustine, etoposide, cytarabine and melphalan) followed by autologous stem cell infusion.

Prior to the approval of Kepivance (palifermin, keratinocyte growth factor) there were no FDA-approved systemic drugs for the treatment or prevention of mucositis due to chemotherapy or radiation therapy. At the present time, Kepivance is approved for preventing mucositis in the autologous transplant setting.[1] The randomized trial that led to the approval of Kepivance involved a total body irradiation (TBI) based regimen. However, many patients receiving autologous stem cell transplants receive chemotherapy alone regimens without TBI. The most frequently used regimens for patients with hematologic malignancies are high-dose Alkeran and BEAM. The effects of Kepivance in patients receiving these regimens were reported at the 2006 ASH meeting.

Researchers from Germany have determined that patients with hematologic malignancies receiving BEAM have a significant incidence of oral mucositis.[2] Prior to performing a randomized trial of Kepivance versus best supportive care, these authors determined base-line risk factors for developing oral mucositis following BEAM. They reported that grade 2 oral mucositis occurred in 30% of patients, grade 3 in 10% of patients, and grade 4 in 4% of patients receiving BEAM. Oral mucositis was higher in women, older patients, in heavily pre-treated patients and those who had received radiotherapy.

Researchers from Lausanne, Switzerland, treated 34 patients with hematologic malignancies with high-dose Alkeran or BEAM with Kepivance prophylaxis for oral mucositis.[3] They compared outcomes to their historical experience. They reported that patients treated with Kepivance had a 17% incidence of grade 2 or greater oral mucositis compared to 44% in the control group. There were no differences in total opioid use, FUO, clinical documented infection, microbial documented infection or bacteremia. Toxicities associated with Kepivance included rash, edema and mouth discomfort.

Researchers from Italy reported preliminary feasibility data on 175 adult patients receiving Kepivance as prophylaxis for oral mucositis in the Italian Early Access Program (EAP).[4] The data presented were similar to data reported elsewhere in this report. These authors concluded that “the use of palifermin in this setting appears to be feasible and was widely accepted by participating physicians and patients.”

Researchers from Germany reported the results of combining Kepivance and Neulasta® (pegfilgrastim) for the prophylaxis of patients with multiple myeloma receiving high-dose melphalan with autologous stem cell support.[5] They treated 15 patients with the Kepivance-Neulasta combination and compared outcomes to 21 patients who received the same melphalan regimen followed by Neulasta alone. They reported that there were no differences in time to recovery of neutrophils or platelets between the two groups. However, they reported a significant reduction in the incidence and severity of oral mucositis and a 3 day reduction in the duration of hospitalization in the Kepivance-Neulasta group. They also reported that Kepivance and Neulasta decreased the need for IV antibiotics and red blood cell transfusions.

Researchers from the University of Georgia reported that Kepivance may reduce platelet transfusion requirements in patients with multiple myeloma receiving high-dose Alkeran with autologous peripheral blood stem cell support.[6] This study involved 36 consecutive patients with multiple myeloma receiving Kepivance and 38 comparable historical controls receiving the same therapy without Kepivance. Patients in the Kepivance group required an average of 1.11 platelet transfusions compared to 2.42 in the historical control group. Forty-six percent of patients in the Kepivance group did not require any platelet transfusions compared to 21% in the control group. When corrected for beginning platelet counts these differences were less apparent. These data are different than the randomized trial involving a TBI-based regimen where no differences in platelet transfusion requirements were observed. These observations will need to be documented in a randomized trial.

Related News

Kepivance® Decreases Oral Mucositis in Patients with Metastatic Colorectal Cancer (11/27/2006)

Kepivance® Reduces Mucositis After Allogeneic Stem Cell Transplantation Without Impact on Acute GVHD (11/09/2006)

Kepivance™ Improves Patient-Assessed Oral Mucositis Following Autologous Stem Cell Transplantation (04/21/2006)

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