Long-Term Safety Outcomes in Patients with Hematological Malignancies Undergoing Autologous Hematopoietic Stem Cell Transplantation Treated with Palifermin to Prevent Oral Mucositis

Abstract

The purpose of our study was to compare long-term safety outcomes (overall survival, disease progression, and incidence of secondary malignancies) between palifermin and placebo in the prevention of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT). Patients were enrolled between 1997 and 2005 into 4 phase I to III studies (3 double-blind placebo-controlled and 1 open-label) conducted at 31 sites in Australia, Europe, and the United States. Survival outcomes (overall survival, progression-free survival) were compared using hazard ratios (HRs) estimated with a Cox model that included treatment group, baseline age, disease type, Eastern Cooperative Oncology Group performance status, country, and presence of prior radiotherapy as covariates. The incidence of secondary malignancies was compared with a chi-square test. A total of 672 patients were randomized into the studies (428 palifermin and 244 placebo). The median follow-up time for subjects alive at last visit was 7.9 years (range, .1 to 14.9) for palifermin and 8.8 years (range, .1 to 14.8) for placebo. Palifermin-treated patients had overall survival (HR, 1.01; 95% confidence interval [CI], .78 to 1.31; P = .921) and progression-free survival times (HR, 1.04; 95% CI, .83 to 1.31; P = .733) that were comparable with placebo-treated patients. Secondary malignancies were reported by 13% of palifermin-treated patients versus 11% of placebo patients (P = .477). Breakdown into secondary hematological malignancies (7% versus 6%) or solid tumors (6% versus 6%) did not suggest any differences between the treatment groups. After a follow-up of up to 15 years, comparable long-term safety outcomes (overall survival, progression-free survival, and incidence of secondary malignancies) were observed for palifermin- and placebo-treated patients undergoing autologous HSCT.

Safety, Pharmacokinetics, and Efficacy of Palifermin in Children and Adolescents with Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplantation: A Pediatric Blood and Marrow Transplant Consortium Trial

“…Theoretically, there is a risk that palifermin may stimulate secondary malignancies, because the KGF receptor is expressed on epithelial cells of many tissues, and it is thus of high importance to study this theoretical risk at exposure in children and adolescents. Long-term follow-up of subjects receiving palifermin in adult hematologic malignancy studies treated with myeloablative therapy and allogeneic HSCT has not shown an increased incidence of secondary malignancies or decrease in PFS or OS over historical data [32]. The PFS and OS in this study did not differ from what would be expected historically in pediatric patients with hematologic malignancies treated in a similar way as patients in this study [33].…”

The Impact of Palifermin Use on Hematopoietic Cell Transplant Outcomes in Children

“…9 Similarly, in a randomized, double-blind trial of adults undergoing allogenic HCT; palifermin treatment had no significant effect on time to engraftment, aGVHD, or survival. 8 …”

“…1 However, cells of the hematopoietic lineage do not express the KGF receptor, and the administration of palifermin for the prevention of OM in patients with hematologic malignancies does not appear to adversely affect other HCT outcomes. 9 However, most of these outcomes, including outcomes pertinent to safety (e.g. mortality and count recovery) were largely evaluated in adult patients.…”

Oncological-Therapy Related Oral Mucositis as an Interdisciplinary Problem—Literature Review

“…Furthermore, survival of patients receiving palifermin and the placebo were almost the same [61]. Moreover, according to Stiff et al, the long term safety outcomes among patients receiving palifermin in oral mucositis treatment and the placebo were comparable [63].…”