Abstract 1131P
Background
Immune checkpoint inhibitors (ICIs) are a standard of care adjuvant treatment option for melanoma patients following the resection of lymph node metastases. ICIs are associated with potentially severe immune-related adverse events (irAEs) and early diagnosis of irAE is of importance. We evaluated the utility of C-reactive protein (CRP) as a biomarker for the early diagnosis of irAEs in melanoma pts treated with ICI in the adjuvant setting, and its potential correlation with relapse-free survival.
Methods
Prospectively collected data from 72 melanoma patients treated with ICIs in the adjuvant setting in a prospective phase II trial (NCT02941744, Schwarze JK et al. JCO. 2019;37(15_suppl):9585) and an observational trial were pooled. CRP-values enveloping 9 defined categories of irAEs were analysed.
Results
A total of 191 irAEs (grade 1 or 2, n=182; grade 3 or 4, n=9) occurred in 64 patients (skin toxicity [n=70], fatigue [n=50], thyroiditis [n=12], musculoskeletal toxicity [n=11], sicca syndrome [n=10], pneumonitis [n=6], colitis [n=4], hepatitis [n=3] and hypophysitis [n=2]). An additional 23 irAEs did not match any of these most frequent categories. In ir-pneumonitis and ir-hypophysitis the median serum CRP-levels exceeded the ULN (5mg/L) with a mean rise of 21.0 mg/L and 9.7 mg/L respectively. Declining CRP-levels were correlated with recovery of an irAE and increases in CRP-level indicated relapse of the irAE. With a median follow-up of 26.5 months 28 patients (39%) were diagnosed with a melanoma relapse. Patients who experienced no irAE were at the highest risk for relapse. Patients diagnosed with an irAE that was associated with an elevated CRP (>2xULN) were at higher risk for relapse as compared to those diagnosed with an irAE and CRP <2xULN (Log Rank, descriptive p-value of .054).
Conclusions
CRP has potential as a biomarker for the early detection of selected irAEs. Monitoring of CRP-levels during adjuvant ICI treatment could help safeguarding adjuvant ICI therapy in daily clinical practice. The observed correlation between irAEs associated with an elevated CRP and risk for recurrence deserves further investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
UZ Brussel.
Funding
Has not received any funding.
Disclosure
J.K. Schwarze: Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Amgen. G. Awada: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Astellas; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer. B. Neyns: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Merck-Serono. All other authors have declared no conflicts of interest.