Abstract 1198P
Background
Anaplastic lymphoma kinase (ALK) rearrangements are detected in 5-7% of NSCLC. ALK may be naturally immunogenic, and ALK autoantibodies are related to a positive outcome in patients (pts) with anaplastic large cell lymphoma (ALCL). The prognosis value of anti-ALK autoantibodies (ab) is unknown in pts with ALK+ NSCLC.
Methods
Between October 2015 and February 2021, we enrolled 24 pts with ALK+ NSCLC and available blood samples collected at disease progression on any ALK tyrosine kinase inhibitor (TKI). Among them, 22 were suitable for ab titration by a semiquantitative immunocytochemical technique. COS-7 cells were used for the transfection with the NPM-ALK plasmid. Then a secondary ab coupled with a peroxidase was added to reveal the antigen-ab reaction. Serum without evidence of antibodies at 1:100 read (absence of cytoplasm marking), was considered negative. ALK ab titer in positive cases corresponded to the last dilution allowing to detect NPM-ALK ab.
Results
Median age was 52 (23-73) years, 11/22 pts (50%) were women, 18 (81,8%) pts received Crizotinib as first TKI, 3 (13,7%) Alectinib and 1 (4,5%) Ceritinib. Median overall survival was 73 months. No differences in terms of toxicity were observed between subgroups. Anti-ALK ab were detected in 3/22 blood samples (13,6%). Pts with detectable anti-ALK ab were younger (36,5 vs 53,0 years, p=0.22). Median follow-up was 53 and 91 months for pts with and without anti-ALK Ab (p=0,29). Among the 19 pts without anti-ALK ab, 3 (15,8%) reported brain metastasis (BM) at cancer diagnosis. Among the pts with no brain involvement at baseline (n=16, 84,2%), half later developed BM. The median time of BM development for pts without anti-ALK ab was 32.5 months (95% CI, 19.5-45.4). None of the 3 pts testing positive for anti-ALK ab developed BM. On-target ALK mutations were found in 2/3 (66,6%) pts presenting anti-ALK ab and in 7/19 (36,8%) negative cases (p 0,54).
Conclusions
Anti-ALK ab were observed in nearly 14% pts with ALK+ NSCLC. Pts with anti-ALK ab did not develop BM during their cancer history. Analysis on 50 patients will be presented.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Prof. B. Besse.
Funding
Has not received any funding.
Disclosure
P. Abdayem: Non-Financial Interests, Personal, Advisory Role: Non-financial support from Pierre Fabre and Eli Lilly outside the submitted work. P. Lavaud: Financial Interests, Personal, Advisory Role: travel accommodations: Astellas-Pharma, AstraZeneca, Ipsen, Janssen Oncology, Mundi Pharma. D. Planchard: Non-Financial Interests, Personal, Invited Speaker: Consulting, advisory role or lectures: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Samsung. Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Financial Interests, Personal, Other: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. F. Barlesi: Non-Financial Interests, Personal, Advisory Role: Personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda, outside the submitted work. J-C. Soria: Financial Interests, Personal, Leadership Role: Shares AstraZeneca, Relay Therapeutics, Gritstone Oncology. Board of Director: Hookipa Pharmaceutical. Was a full time employee at AstraZeneca from September 2017 to December 2019. V. Ribrag: Non-Financial Interests, Personal, Advisory Role: Mylan, Celgene, Bristol Myers Squibb, and Roche; Personal fees from Bristol Myers Squibb and AstraZeneca, and funding for clinical trials from AbbVie, Agios, Amgen, Argen-X, Debiopharm, Eisai, Forma Therapeutics, Ge; Non-Financial Interests, Personal, Funding: Bristol Myers Squibb and AstraZeneca; Non-Financial Interests, Personal, Sponsor/Funding: AbbVie, Agios, Amgen, Argen-X, Debiopharm, Eisai, Forma Therapeutics. L. Friboulet: Non-Financial Interests, Personal, Advisory Role: Grants from Incay and grants from Debiopharm outside the submitted work. B. Besse: Non-Financial Interests, Personal, Advisory Board: AbbVie; Non-Financial Interests, Personal, Advisory Role: Amgen; Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: Biogen; Non-Financial Interests, Personal, Advisory Role: Blueprint Medicines; Non-Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Personal, Advisory Board: Ipsen, Merck, MSD, Nektar, Onxeo, Pfizer, PharmaMar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharm 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal T. All other authors have declared no conflicts of interest.