Abstract 989P
Background
Pts receiving antiPD1 +/- antiCTLA4 immune checkpoint inhibitors (ICI) can develop severe irAEs. Our group used a customized autoantigen (autoAg) microarray (Chruscinski et al. PLOS One 2016) to detect autoantibodies (autoAb) related to autoimmune disorders. We hypothesized that autoantibodies (autoAb) profiling could be used to identify patients at risk for irAEs.
Methods
Plasma obtained from cancer pts receiving ICI in a clinical trial (NCT03686202) at baseline and 3-4 weeks post ICI was analyzed. Samples from healthy controls (hc) were used for comparison. Custom arrays with 162 autoAg incubated with plasma were probed with fluorescent-labeled secondary Ab to detect IgG and IgM reactivity. Total IgG and IgM pre and post ICI were measured by enzyme-linked immunosorbent assay. Differences of median fluorescent intensity (MFI) and total IgG and IgM were analyzed with Wilcoxon sign rank test and binary logistic model.
Results
Thirty pts were included, 17 had G≥2 irAEs. Median age was 67y (24-81), 19 (63%) were male. Melanoma and head and neck were the most frequent tumors with 14 pts each (47%). Eighteen (60%) pts received anti-PD1, 12 (40%) antiPD1+antiCTLA4 (median 4 cycles (1-18)). G≥2 irAEs of interest included: pneumonitis (6), hypothyroidism (5), colitis (3), hepatitis (3), meningitis (1), hypophysitis (1), myocarditis (1) and diabetes (1). We observed higher baseline levels of 6 specific IgG in pts with irAEs vs those without irAEs (p<0.05). IgG anti-SMD3 and anti-MPO predicted irAEs in univariate analysis (p<0.05). Four AutoAb were greater at baseline in pts without irAEs (p<0.05). Baseline elevated autoAb related to tissue specific autoimmunity and their increase post ICI corresponded to irAEs of the relative organ (e.g. myocarditis: baseline IgG anti-cardiac myosin MFI 7200, post-ICI MFI 12000; hc median MFI 1441). Greater levels of total IgM were observed post ICI in pts with irAEs (p <0.001).
Conclusions
Our analysis indicates elevated baseline levels of specific autoAb in cancer pts with and without irAEs. These data suggest that the baseline profile of autoAb and early changes post ICI may identify pts at high risk for irAEs. Validation in an independent dataset is ongoing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
A. Spreafico's research founding.
Disclosure
A.R. Hansen: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Institutional, Funding: Karyopharm Therapeutics; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Personal, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Roche/Genentech; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: AstraZeneca/MedImmune; Financial Interests, Institutional, Funding: Astellas Pharma; Financial Interests, Institutional, Funding: Macrogenics. L.L. Siu: Financial Interests, Personal, Advisory Board: Arvinas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GeneSeeq; Financial Interests, Personal, Advisory Board: Janpix; Financial Interests, Personal, Advisory Board: Loxo; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Morphosys; Financial Interests, Personal, Advisory Board: Navire; Financial Interests, Personal, Advisory Board: Oncorus; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Relay Therapeutics; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Rubius; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Symphogen; Financial Interests, Personal, Advisory Board: Tessa; Financial Interests, Personal, Advisory Board: Treadwell Therapeutics; Financial Interests, Personal, Advisory Board: Voronoi; Financial Interests, Personal, Other, Spouse is co-founder: Treadwell Therapeutics; Financial Interests, Personal, Other, Spouse has stock ownership: Agios; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Avid; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Boerhinger-Ingelheim; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator: Intensity Therapeutics; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Mirati; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Roche/Genentech; Financial Interests, Institutional, Principal Investigator: Shattucks; Financial Interests, Institutional, Principal Investigator: Symphogen. S. Saibil: Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Other, Travel accomodation: Iovance Biotherapeutics. L. Stayner: Financial Interests, Institutional, Other, Travel accomodation: Astellas. M. Yanekina: Financial Interests, Personal, Other, Travel accomodation: Roche. P. Bedard: Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: Servier; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: PTC Therapeutics; Financial Interests, Institutional, Funding: Nektar; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Seattle Genetics; Financial Interests, Institutional, Funding: Mersana; Financial Interests, Institutional, Funding: Immunomedics; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Bicara Therapeutics. A.R. Abdul Razak: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Adaptimmune; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal and Institutional, Funding: Deciphera; Financial Interests, Personal and Institutional, Funding: Karyopharm Therapeutics; Financial Interests, Personal and Institutional, Funding: Pfizer; Financial Interests, Personal and Institutional, Funding: Roche/Genentech; Financial Interests, Personal and Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Funding: MedImmune; Financial Interests, Personal and Institutional, Funding: Amgen; Financial Interests, Personal and Institutional, Funding: GlaxoSmithKline; Financial Interests, Personal and Institutional, Funding: Blueprint Medicines; Financial Interests, Personal and Institutional, Funding: Merck; Financial Interests, Personal and Institutional, Funding: Abbvie; Financial Interests, Personal and Institutional, Funding: Adaptimmune; Financial Interests, Personal and Institutional, Funding: Iterion Therapeutics. B. Coburn: Financial Interests, Institutional, Funding: Nubiyota; Financial Interests, Institutional, Funding: Sanofi. A. Spreafico: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Oncorus; Financial Interests, Personal and Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Funding: Novartis; Financial Interests, Personal and Institutional, Funding: Merck; Financial Interests, Personal and Institutional, Funding: Symphogen; Financial Interests, Personal and Institutional, Funding: AstraZeneca/MedImmune; Financial Interests, Personal and Institutional, Funding: Bayer; Financial Interests, Personal and Institutional, Funding: Surface Oncology; Financial Interests, Personal and Institutional, Funding: Janssen Oncology; Financial Interests, Personal and Institutional, Funding: Northern Biologics; Financial Interests, Personal and Institutional, Funding: Replimune; Financial Interests, Personal and Institutional, Funding: Roche; Financial Interests, Personal and Institutional, Funding: Alkermes; Financial Interests, Personal and Institutional, Funding: Array BioPharma; Financial Interests, Personal and Institutional, Funding: GlaxoSmithKline. All other authors have declared no conflicts of interest.