ABSTRACT
Background: Immune Checkpoint Blockade (ICB) is moving from metastatic to curative setting in different diseases including NSCLC. While for metastatic disease radiological endpoints are currently the standard surrogate marker of benefit from ICBs, based on RECIST or PERCIST criteria, in neoadjuvant setting they often underestimate the response and then pathological response (PR) criteria were developed to evaluate Major PR (MPR), defined as ≤10% viable tumor cells after neoadjuvant treatment, and PR, defined as less than 50% residual tumor cells. Anyway, a non-invasive approach to determine the response to treatment is still an unmet need. Methods: PRINCEPS was a phase 2 clinical trial including limited-stage (IB-IIIA) NSCLC patients who received one administration of atezolizumab before surgery. 18-F FDG PET was performed within 28 days and after 15-22 days from atezolizumab. Surgery was performed at day 22-29 from atezolizumab. PET derived parameters including MTV and TLG was extracted by experienced nuclear physicians. Results: 30 patients were enrolled, all received A and underwent surgical resection after a median of 23 days. MPR was identified in 4, pPR in 8 tumors. Paired PET were available for 28 pts. Mean time from A to PET was 18 days (IQR 3.5). Total TLG and MTV reduction was not correlated with percentage of pPR (p=0.117 and p=0.843, respectively). Reduction of MTV (Pearson correlation 0.509, p=0.006) and TLG (Pearson correlation 0.562, p=0.002) in the primary tumor were strongly correlated with pPR, while no correlation was observed between percentage of pPR and variation in tumor diameters by RECIST criteria (-0.24, p=0.2) nor metabolic response (-0.12, p=0.55). The appearance of metabolically active hilar and mediastinal, non-pathological lymph nodes (LN) was noted in 12/28 patients, and specifically in. 2 out of 4 MPR and 5 out of 8 pPR. A trend toward an higher pPR was observed with LN appearance (mean 52% reduction in pts with LN appearance vs 29% without, p 0.061), probably reflecting immune activation. LN appearance was associated with hyperplasia and histiocytosis in resected, non-metastatic LNs. Conclusions: PET is able to early detect tumor response in localized NSCLC patients treated with ICBs in neoadjuvant setting. Clinical trial identification: NCT02994576. Legal entity responsible for the study: Institut Gustave Roussy. Funding: Roche. Disclosure: N. Chaput-Gras: Financial Interests, Personal, Advisory Board, Strong-Iopredi Scientific Advisory Board: AstraZeneca;Financial Interests, Institutional, Invited Speaker, Educational Session On Immune Cell Death: Servier;Financial Interests, Institutional, Expert Testimony, Expertise On Immune Cell Death Biomarkers: Servier;Financial Interests, Personal, Invited Speaker: Cytune Pharma;Financial Interests, Institutional, Research Grant, Research grant to identify immune biomarkers associated to clinical response in patients treated with agonistic mAbs: GSK;Financial Interests, Institutional, Research Grant, Preclinical studies in mice: GSK;Financial Interests, Institutional, Research Grant, Immune profiling of Head & Neck tumors: Sanofi. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen;Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen;Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre;Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Resea ch Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, MSD, Boehringer-Ingelheim;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, Takeda, Sanofi;Financial Interests, Personal, Expert Testimony: Ose Immunotherapeutics;Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD;Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda;Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Eisai, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. All other authors have declared no conflicts of interest.
ABSTRACT
Introduction La vaccination contre la Covid a été recommandée chez les patients transplantés d’organes solides en début d’année 2021, selon un schéma comprenant 3 doses chez les patients n’ayant pas présenté d’infection par la Covid 19 et selon un schéma comprenant 2 injections chez les patients ayant été infectés par la Covid. Méthodes Nous avons étudié la réponse vaccinale après un schéma complet dans une cohorte de patients transplantés pulmonaires et cardiopulmonaires à l’hôpital Marie Lannelongue. Selon les recommandations de l’OMS, l’absence de réponse vaccinale est définie par une sérologie dont le taux est<30 BAU/ml. Le taux d’Anticorps considéré comme protecteur est un taux>260 BAU/ml. Les patients dont le taux est compris entre 30 et 260 BAU/ml sont considérés comme faiblement répondeurs. La sérologie a été effectuée entre 1 et 3 mois après la dernière injection. Résultats Dans notre cohorte comprenant 373 patients, une sérologie Covid a pu être obtenue chez 75% des patients. Une absence complète de séroconversion a été constatée chez 75% des patients. Une séroconversion avec un taux d’anticorps considéré comme protecteur n’a été obtenu que chez 14% des patients, dont la moitié a présenté une infection par la Covid. Par ailleurs, 11% des patients ont été faiblement répondeurs. Conclusion Notre étude mono-centrique suggère une très faible réponse vaccinale chez les patients transplantés pulmonaires et cardiopulmonaires, suggérant la réalisation d’une 4e dose chez les patients partiellement répondeurs et/ou un traitement par anticorps monoclonaux spécifiques chez les patients non répondeurs.