Palifermin Treatment in Patients Receiving High Dose Melphalan or BEAM Prior to Autologous Peripheral Blood Stem-Cell Transplantation.

Background. Oral mucositis (OM) is a common complication of high-dose (HD) chemotherapy conditioning regimens used with peripheral blood stem-cell transplantation (PBSCT). Severe grades of OM are associated with higher morbidity such as infections, need for total parenteral nutrition (TPN), opioid analgesics and prolonged hospitalization and has been historically underreported. Recent epidemiology reveals an incidence of severe OM of 50–60%. Moreover, OM is reported by patients as the worst and most debilitating complication of PBSCT. The keratinocyte growth factor, palifermin, stimulates the growth, differentiation, migration, and survival of epithelial cells. Palifermin is now approved in the US and the EU to decrease the incidence, duration, and severity of OM in patients (pts) with hematological malignancies requiring autologous PBSCT.

Objective. This report describes the treatment of 60 pts who received palifermin through an early access program in Belgium. We evaluated the effect of palifermin on OM in pts with multiple myeloma or non-Hodgkin’s lymphoma receiving HD melphalan (HD Mel) or BEAM conditioning regimen, respectively, prior to autologous PBSCT.

Methods. The pts received palifermin (IV bolus: 60 μg/kg/day) for 3 days before and 3 days after HD Mel or BEAM. The common OM prevention strategy included basic oral hygiene, mouth washes and oral cryotherapy during HDM administration (n=9). For each patient, follow-up data were collected on mucositis grading, duration of hospitalization, neutropenic fever, treatment with G-CSF, IV antibiotics, opioids, and TPN. The grade of OM during treatment was assessed according to the WHO oral-toxicity scale (grade 0 to 4). Drug-related adverse events were also recorded.

Results. Thirty pts received HD Mel and 30 pts received BEAM before PBSCT. All 60 pts received at least 3 palifermin bolus injections; the scheduled doses (6 bolus) were administered to 55 (91%) of 60 pts. Analysis of the follow-up data revealed that 10 (16%) pts experienced no OM. Furthermore, a low incidence (31%) of severe (grade 3 and 4) OM was observed with each conditioning regimen. The median duration of severe OM with the HD Mel regimen was 7 days (range 3–27) contrasting with a median OM duration of 3 days (range 2–12) with the BEAM regimen. Two pts in each regimen required prolonged hospitalization due to OM. With either regimen, neutropenic fever and use of IV antibiotics were common (70% of pts), while bacteremia was infrequent (20% of pts). Myeloid growth factors were administered post PBSCT to the majority of pts. Forty percent (40%) of HD Mel-treated pts and 26% of BEAM-treated pts required opioid analgesics. The percentages of pts receiving TPN were similar in the 2 conditioning regimens (66% of all pts). TPN was used in 16 (84%) pts with severe OM and in 24 (58%) pts with no or grade 1–2 OM. Adverse events clearly related to palifermin were reported in 25 (41%) of 60 pts. The most common adverse events included rash (18 events, 8 severe), disorders of tongue and oral mucosa (13 events, 2 severe), edema (10, no severe) and pruritus (7, no severe).

Conclusions. These results indicate that palifermin use prior to HD Mel or BEAM and immediately following the transplantion may provide effective support in the prophylaxis of severe OM in pts undergoing autologous PBSCT, without major toxicity.