Systemic Corticosteroids’ Impact on Survival in Metastatic Uveal Melanoma

All immunotherapies that expeditiously stimulate T cells, such as T cell engagers, can elicit cytokine release syndrome (CRS). Tebentafusp, a bispecific T cell receptor (TCR) targeting gp100 and CD3, has been observed to produce cutaneous adverse events (AEs) owing to gp100+ melanocytes in the skin. Chronic rhinosinusitis (CRS) and adverse skin events (AEs) may necessitate treatment with short-term corticosteroids, which can also serve as pre-medication for subsequent tebe doses. In this report, we present the initial examination of the administration of systemic corticosteroids and its association with therapeutic effectiveness in a Phase 3 clinical trial involving a T cell engager. Retrospective analyses were conducted on phase 3 clinical trial treatment arm with registration number NCT03070392, which focused on patients with previously untreated metastatic uveal melanoma (mUM) who were positive for HLA-A*02:01 (N = 245). As a result of the low incidence of severe adverse events observed in Phase 1 clinical trials, the administration of prophylactic corticosteroids was not deemed mandatory. The study conducted a safety population analysis to investigate the correlation between corticosteroid usage (initiated within 30 days of the first tebe dose) and overall survival (OS) using landmark analyses. The multivariate analyses were adjusted for significant patient characteristics and adverse events of particular medical interest, including cytokine release syndrome (CRS), dermatitis, and elevated liver function test (LFT) levels. The study examined the efficacy of different types of steroids, specifically hydrocortisone and others, as well as the duration of treatment, comparing one day versus more than one day.

During the Phase 3 clinical trial, 26% (64 out of 245) of patients were administered new systemic corticosteroids within 30 days after receiving the initial dose of Tebe. The primary reason for administering these corticosteroids was to manage adverse events (88% or 56 out of 64 patients) or as a pre-medication due to previous adverse events (22% or 14 out of 64 patients). Out of 64 patients, 25 were administered corticosteroids exclusively for one day. The most commonly reported adverse events (AEs) with a frequency of 15% or greater were rash (18 out of 64 patients, 28%), cytokine release syndrome (CRS) (15 out of 64 patients, 23%), and hypotension (12 out of 64 patients, 19%). The logistic regression model revealed that an elevated baseline lactate dehydrogenase (LDH), the primary prognostic marker, exhibited the strongest association with administering corticosteroids (P = 0.01). The multivariate analysis revealed that corticosteroids did not significantly differ in overall survival (OS) (HR 1.41, 95% CI 0.83-2.4, P = 0.2). Moreover, this effect remained consistent in patients with or without symptoms such as CRS, rash, or LFT elevation, as indicated by the non-significant interaction tests (P> 0.2). There was no significant variation in overall survival (OS) based on the type of corticosteroid administered or the duration of administration, whether for a single day or more than one day.

This report presents the initial findings of a phase 3 clinical trial evaluating the effects of systemic corticosteroids on the survival outcomes of patients receiving T cell-engaging cancer therapy. A significant proportion of patients undergoing this treatment (84%) did not necessitate the administration of corticosteroids (74%) or were prescribed a single-day course (10%). The primary indication for corticosteroid administration was an acute adverse event, such as cytokine release syndrome and dermatological manifestations. The administration of corticosteroids by the predetermined negative event guidelines did not demonstrate any notable effect on overall survival.

Source: https://meetings.asco.org/abstracts-presentations/210257

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03070392

Alexandra Ikeguchi, Joseph J. Sacco, Jason J. Luke, T.R. Jeffry Evans, Brendan D. Curti, Kevin B. Kim, Shaad Essa Abdullah, Claire Watkins, Ozgur Karakuzu, Paul D. Nathan/Analysis of the effect of systemic corticosteroids on survival from tebentafusp in a phase 3 trial of metastatic uveal melanoma/J Clin Oncol 40, 2022 (suppl 16; abstr 9584)
DOI10.1200/JCO.2022.40.16_suppl.9584