Fixed-Dose Versus Weight-Adapted Immune Checkpoint Inhibitor Therapy in Melanoma: A Retrospective Monocentric Analysis of Efficacy and Immune-Related Adverse Events

Abstract

Changes in the dosing schedules for immune checkpoint inhibitors, specifically nivolumab and pembrolizumab, in the treatment of metastatic melanoma, were introduced based on pharmacokinetic data and analysis of pre-existing clinical trial data in the absence of new clinical trials. Therefore, we sought to provide real-world data examining whether fixed-dose therapy (FDT) or weight-adapted therapy (WAT) influenced progression-free (PFS) and overall survival (OS), and the incidence of immune-related adverse events (irAEs). The electronic case notes of all patients (n = 77) treated with immune checkpoint inhibitor immunotherapy (ICI) in the first-line setting for melanoma in the Department of Dermatology, University of Luebeck, between the 1 January 2017 and the 31 December 2020, were retrospectively analysed. Although a higher proportion of patients in the WAT cohort were treated in the palliative setting, there were no correlations between dosing schedule, renal function, or BMI and PFS. Moreover, there were no differences between the cohorts in terms of PFS, OS, or the number and nature of irAEs. An elevated serum S100 concentration was associated with a decreased mean PFS in the FDT cohort (p < 0.001). This study, although inherently limited by its retrospective and monocentric nature, provides reassuring evidence that dosing schedule and pre-existing comorbidities do not influence efficacy or the irAE profile of ICI therapy in the management of melanoma.

Keywords: Real World Data; cancer; fixed dose; immunotherapy; melanoma.

Figure 1

Flow chart of the study population.

Figure 2

Progression-free and overall survival. There were no significant differences between the FDT and WAT cohorts.

Figure 3

Patient-specific factors and progression-free survival. Age (A), sex (B) and body mass index (C) had no significant effects on PFS in either cohort.

Figure 4

Disease-specific factors and irAEs. Whilst BRAF status had no effect on PFS (A), an elevated S100 concentration had a significant effect on PFS in the FDT group (B). There were no differences in the incidence or number of irAEs (C,D) between the cohorts, and the number of irAEs did not impact PFS (E,F).