Immunogenicity of COVID‑19 Vaccines in Lung Cancer Patients: A SOLID Substudy Interim Analysis

Background: Although vaccination of patients with lung cancer against COVID-19 is supported by the major international cancer societies worldwide, information on the efficacy of anti‑SARS‑CoV‑2 vaccines in this population is limited. We therefore aimed to evaluate the safety and immunogenicity of COVID‑19 vaccines, and durability of the immune response in fully vaccinated lung cancer patients.Methods: This was a substudy of the prospective, nationwide, longitudinal, multicenter SOLID study (Seroprevalence and immunological memory against SARS-CoV-2 in lung cancer patients), aimed at evaluating COVID‑19 vaccine immunogenicity and the durability of the immune response in fully vaccinated lung cancer patients. Eligible participants were adults aged ≥ 18 years, diagnosed with lung cancer, regardless of whether they had had COVID‑19 or not, and who were fully vaccinated against COVID‑19. Serum anti‑SARS‑CoV‑2 IgG antibody levels were quantitatively assessed approximately two weeks and six months after receipt of the last dose of the vaccine using a chemiluminescent microparticle immunoassay. The threshold value for seropositivity was established at 7.1 standardized binding antibody units (BAU) per mL. We estimated the odds ratio for being seronegative for anti-SARS-CoV-2 antibodies after vaccination using multivariable logistic regression analysis.Findings: From March 3, 2021 to September 30, 2021, 1976 lung cancer patients were enrolled in 37 Spanish hospitals, most of whom had stage IV disease (67.6%) and were receiving active cancer treatment (82.6%). All patients were fully vaccinated against COVID‑19. High levels of anti‑SARS‑CoV‑2 IgG antibody titers were observed in the vast majority of patients (95.2%) two weeks after vaccination (655.45 BAU/mL [95% CI 593.5-723.8]). Only ten patients (0.5%) contracted SARS‑CoV‑2 infection within a median of 19 days (IQR 5–76) after full vaccination. No significant differences were found in the probability of being seronegative for anti‑SARS‑CoV‑2 IgG antibodies after full vaccination between patients who were receiving active cancer treatment and those who were not (p = 0.966). Multivariate logistic regression analysis showed that performance status ≥ 2 and the presence of comorbidities were independently associated with a higher probability of being seronegative for anti-SARS‑CoV‑2 IgG antibodies after full COVID‑19 vaccination (OR 4.38, 95% CI 2.24–8.55; p < 0.001 and OR 3.43, 95% CI 1.32–8.87; p = 0.011, respectively). The administration of anticancer immunotherapy (OR 0.25, 95% CI 0.14–0.43; p < 0.001) or oral targeted therapy (OR 0.12, 95% CI 0.04–0.42; p = 0.001), and immunization with mRNA-1273 COVID‑19 vaccine (OR 0.41, 95% CI 0.24–0.71; p = 0.001) were factors independently associated with decreased odds of being seronegative for anti-SARS‑CoV‑2 IgG antibodies after vaccination.Interpretation: Lung cancer patients can safely achieve a strong immune response against SARS‑CoV-2 after full vaccination against COVID-19, regardless of whether they are receiving active cancer treatment or not. Patients with performance status ≥ 2 and/or comorbidities have a higher probability of being seronegative for anti‑SARS‑CoV‑2 IgG antibodies after full COVID‑19 vaccination, while this probability is lower among patients who are receiving immunotherapy or oral targeted therapy or who received the mRNA-1273 COVID‑19 vaccine.Clinical Trial Registration Details: This trial is registered at ClinicalTrials.gov, NCT04407143.Funding Information: Roche Pharma and the European Union Horizon 2020 Research and Innovation Program.Declaration of Interests: MP reports grants, personal fees and non-financial support from Bristol Myers Squibb, Roche, and AstraZeneca, and personal fees from Merck Sharp & Dohme andTakeda, outside of the submitted work. AE reports personal fees and non-financial support from Merck Sharp & Dohme, Roche, Lilly, PharmaMar, and AstraZeneca, personal fees from Bayer, and non-financial support from Bristol Myers Squibb and Pfizer, outside of the submitted work. HA reports personal fees from AstraZeneca and Ferrer, and non-financial support from Angelini Pharma, outside of the submitted work. CA reports personal fees and non-financial support from Roche and Pierre Fabre, and personal fees from Bristol Myers Squibb, AstraZeneca, Merck Sharp & Dohme, Pfizer, and Novartis, outside of the submitted work. VC reports personal fees from Roche, Bristol Myers Squibb, Merck Sharp & Dohme, and AstraZeneca, outside of the submitted work. XMR reports personal fees and non-financial support from Roche, and personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, and AstraZeneca, outside of the submitted work. OJV reports personal fees from Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Roche, AstraZeneca, Lilly, Takeda, and Pfizer, outside of the submitted work. ALM reports personal fees from AstraZeneca, Merck Sharp & Dohme, and Roche, outside of the submitted work. BC reports personal fees and non-financial support from Pierre Fabre, Roche, and Novartis, and personal fees from Sanofi, Bristol Myers Squibb, Rovi, AstraZeneca, and Leo Pharma, outside of the submitted work. SC reports personal fees and non-financial support from Roche and non-financial support from Lilly, GlaxoSmithKline, and Pfizer, outside of the submitted work. FF, GLV, MS, PD, EC, JG, JM, EI, MM, JBB, MG, AB, CLG, AdB, TdP, GS, JR, BE, JLMC, and EdB declare no competing interestsEthics Approval Statement: All participants gave their informed consent in writing prior to enrollment in the study. The study was conducted according to the approved protocol and all applicable laws and regulations, including the ISPE Guidelines for Good Pharmacoepidemiology Practices (GPP), the Spanish Royal Decree 957/2020, of November 3, 2020, regulating observational studies of medicinal products for human use in Spain, and the provisions of the Declaration of Helsinki. The study was approved in 2020 by the Spanish Agency for Medicines and Medical Devices (AEMPS) and registered on the ClinicalTrials.gov database (NCT04407143). The study protocol was reviewed and approved by the institutional review board of Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain (No. PI 81/20).