Palifermin administered pre and post radiochemotherapy conditioning has previously been shown to significantly reduce the incidence and duration of severe oral mucositis (OM) in patients undergoing autologous stem cell transplantation (ASCT). This randomized clinical trial (RCT) aimed to study the efficacy and safety of palifermin when administered in two different dosing regimens in a chemotherapy-only conditioning setting.
The efficacy of palifermin relative to placebo was investigated with palifermin given either pre/post high-dose melphalan (HDM) or pre HDM only in patients with multiple myeloma (MM) undergoing ASCT. Assessment of oral mucositis was primarily based on WHO grades (0/1, 2, 3 or 4) and safety primarily on adverse event (AE) reporting.
281 patients (mean age 56 ± 8 years) were enrolled at 39 centers; 224 patients were randomized to receive palifermin and 57 patients to receive placebo. In the palifermin group, 109 patients were randomized to the pre-only arm, receiving palifermin (60 μg/kg/day) iv for 3 consecutive days before HDM and 115 subjects were randomized to the pre/post arm receiving palifermin on 3 consecutive days before HDM and again on 3 consecutive days after ASCT. The number of subjects actually receiving study drug in the these two arms was 109 and 111, respectively. Assessments of OM and safety were made daily until 32 days post transplant or hospital discharge.
There was no difference in maximum severity of OM between placebo and palifermin administered pre/post HDM (odds ratio: 0.7 [CI: 0.4, 1.3]) or pre HDM (odds ratio: 1.2 [CI: 0.6, 2.4]). Severe OM (WHO grade 3 and 4) occurred in 37% (placebo), 38% (pre/post-HDM) and 24% (pre-HDM) of the patients. A total of 275 patients (99.3%) experienced at least 1 AE during the study. There were more serious AEs and AEs reported as treatment related by the investigators for patients in the pre/post HDM arm, and less in the pre-HDM arm but still more than in the placebo arm.
Overall, no statistically significant differences were observed between placebo and either the palifermin pre-post HDM arm or pre-only HDM arm for maximum severity of OM in this clinical setting with a chemotherapy conditioning regimen of short duration and a comparably low incidence of severe oral mucositis. The pre-only group, however, showed a numerically better result than placebo for the primary and most of the secondary efficacy endpoints. Patients treated with palifermin in the pre HDM arm experienced a more favorable safety profile than the pre/post HDM arm. Possible explanations for the apparent discrepancy compared to previously published trials might be differences in high dose chemotherapy and/or the shorter time interval between the pre and post doses in this study. The impact of the timing of the palifermin post-dose in relation to the pre-dose and in relation to the onset of manifest OM and pathogenesis thus needs to be further explored.
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