Abstract 1863P
Background
Immune checkpoint inhibitors blocking programmed cell death 1 (PD-1) have been associated with the occurrence of severe (grade ≥3) adverse events (AEs) in 7-20% of patients. A better understanding of risk factors for the development of grade ≥3 AEs may aid clinical monitoring and decision-making. We therefore aimed to explore determinants of the occurrence of grade ≥3 AEs during anti-PD-1 monotherapy.
Methods
Patients starting nivolumab or pembrolizumab between July 2015 and Jan 2020 and prospectively included in the Dutch MULTOMAB-trial (NL6828), were followed for grade ≥3 AEs until May 2020. Multivariable (backward selection) cox regression analysis was used to explore the associations between occurrence of a first grade ≥3 AE with patient- and treatment-related characteristics, first for the total cohort, and separately for the melanoma and NSCLC cohorts. Covariates used in the analysis were: tumor type, age, gender, prior treatment, WHO performance status (WHO PS), type of PD-1 inhibitor, histology (NSCLC only), and baseline LDH and treatment setting (melanoma only).
Results
554 patients treated with anti-PD1 monotherapy for various tumor types were prospectively included. Overall, 64 patients (12%) experienced at least one grade ≥3 AE during follow-up (75 grade ≥3 AEs in total), most commonly being colitis (n=22), hepatitis (n=10), skin toxicity (n=9) or pneumonitis (n=9). None of the covariates were associated with the occurrence of a first grade ≥3 AE in the total cohort. Within the melanoma cohort (n=231), age ≥65 years was significantly associated with the occurrence of grade ≥3 AEs (HR=2.4; 95%CI:1.1-5.5;p=0.04). None of the covariates were predictive of grade ≥3 AEs in the NSCLC cohort (n=181). However, grade ≥3 AEs were unevenly distributed across WHO PS, as none of the WHO PS=0 patients experienced high grade AEs.
Conclusions
Surprisingly, despite the large number of co-variates, no patient- or treatment-related characteristics were predictive for the occurrence of grade ≥3 AEs during anti-PD-1 therapy across tumor types. The increased risk of grade ≥3 AEs in elderly patients with melanoma and impact of WHO PS on incidence of grade ≥3 AEs in NSCLC requires further investigation.
Clinical trial identification
NL6828.
Editorial acknowledgement
Legal entity responsible for the study
Erasmus Medical Center.
Funding
Has not received any funding.
Disclosure
M.W.J. Schreurs: Financial Interests, Personal, Writing Engagements: Thermo Fisher; Financial Interests, Personal, Invited Speaker: Thermo Fisher; Financial Interests, Personal, Invited Speaker: Biogen; Financial Interests, Personal, Advisory Role: Coleman Research; Financial Interests, Personal, Sponsor/Funding: Thermo Fisher. A.A.M. van der Veldt: Financial Interests, Institutional, Other, Consultancy: BMS; Financial Interests, Institutional, Other, Consultancy: MSD; Financial Interests, Institutional, Other, Consultancy: Merck; Financial Interests, Institutional, Other, Consultancy: Sanofi; Financial Interests, Institutional, Other, Consultancy: Pfizer; Financial Interests, Institutional, Other, Consultancy: Ipsen; Financial Interests, Institutional, Other, Consultancy: Eisai; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Institutional, Other, Consultancy: Pierre Fabre; Financial Interests, Institutional, Other, Consultancy: Novartis. J.G. Aerts: Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: Boehringer Ingelheim; Financial Interests, Personal, Other: Amphera; Financial Interests, Personal, Other: Eli-Lilly; Financial Interests, Personal, Other: Takeda; Financial Interests, Personal, Other: Bayer; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: BIOCAD; Non-Financial Interests, Personal, Other, Patent licensed: Amphera. R.H. Mathijssen: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Servier; Non-Financial Interests, Personal, Other, patent: Pamgene; Financial Interests, Institutional, Other, Investigator-initiated research: Astellas; Financial Interests, Institutional, Other, Investigator-initiated research: Bayer; Financial Interests, Institutional, Other, Investigator-initiated research: Boehringer-Ingelheim; Financial Interests, Institutional, Other, Investigator-initiated research: Cristal Therapeutics; Financial Interests, Institutional, Other, Investigator-initiated research: Pamgene; Financial Interests, Institutional, Other, Investigator-initiated research: Pfizer; Financial Interests, Institutional, Other, Investigator-initiated research: Novartis; Financial Interests, Institutional, Other, Investigator-initiated research: Roche; Financial Interests, Institutional, Other, Investigator-initiated research: Sanofi; Financial Interests, Institutional, Other, Investigator-initiated research: Servier. All other authors have declared no conflicts of interest.