A Randomized Phase II Study Evaluating the Efficacy, Safety and Cost-Effectiveness of Pegfilgrastim and Filgrastim After High Dose Chemotherapy and Autologous Stem Cell Transplantation In Patients with Lymphoma and Myeloma (PALM Study).
Authors: Sebban Catherine , Lefranc Anne , Perrier Lionel , Moreau Philippe , Espinouse Daniel , Moles-Moreau Marie Pierre , Kammoun Leila , Ghesquieres Herve , Segura-Ferlay Celine , Bay Jacques-Olivier , Lissandre Severine , Pérol David , Michallet Mauricette , Quittet Philippe 
Published: October 2019

Abstract
Abstract 3479

Objective:
To assess the efficacy, safety, and cost-effectiveness of a single injection of Pegfilgrastim (P) 6mg given at D5 or Filgrastim (F) 5μg/kg/day subcutaneously from D5 to the end of neutropenia after reinjection of stem cells in patients with lymphoma or myeloma.

Patients and methods:
The PALM study was an open, multicentre randomized phase II trial. Patients had to be at least 18 years old, with a diagnosis of lymphoma or myeloma, a cryopreserved graft of at least 2.10 CD34/kg, must have had a conditioning regimen without irradiation and an intensive chemotherapy. Eligible pts were 1:1 randomly assigned to P 6mg subcutaneously at D5 or F 5μg/kg/day subcutaneously from D5 to the end of neutropenia (absolute neutrophil count (ANC) >0.5G/L). Randomization was stratified on underlying disease and center. The primary efficacy endpoint was the mean duration of febrile neutropenia (FN) defined as ANC <0.5 G/L and temperature >38°C. Assuming a mean duration of FN of 4 days (SD 3.7), sample size (75 pts per arm) was calculated in order to estimate, with a precision of 0.85 day, a two-sided 95% confidence interval on the mean duration of FN in P arm. No formal comparison between arms was planned for the primary endpoint. The randomization was intended to afford a substantial degree of re-assurance that the historical control value chosen to plan the sample size was appropriate. Key secondary objectives were to estimate, for each treatment regimen, the respective tolerance profile and to compare the cost-effectiveness of the two strategies. The time horizon of the clinical and cost-effectiveness analysis was 100 days. All analyses were performed in the intent-to-treat population, which included all randomly assigned patients. For the economic assessments, a microcosting approach from the hospital perspective was used. Costs (2009 Euros) between P and F were compared using a Mann-Whitney U nonparametric test. Probabilistic sensitivity analyses were conducted using 1000 non-parametric bootstrap replications.

Results:
From October 2008 to September 2009, 151 pts were randomized. Clinical and demographic data were similar in both groups except for older age in the P arm. No grade 3 or 4 adverse event related to the drugs was notified. Data suggested that patients receiving P had similar or slightly better clinical outcomes. Especially, mean duration of FN were 3.07 (SD 1.96) and 3.29 (SD 2.54) days in the P and the F arms, respectively.

Conclusions:
Our findings suggest that Pegfilgrastim, at least as efficient and safe than Filgrastim on clinical outcomes, strictly dominates Filgrastim in terms of economic outcomes, i.e. had better effectiveness and lower costs, on most common intermediate efficacy criteria. Therefore, Pegfilgrastim should be considered as a standard of care in patients with lymphoma and myeloma after high-dose chemotherapy and autologous stem cell transplantation.
This study was partly supported by Amgen France S.A.S.

Disclosures:
No relevant conflicts of interest to declare.