CD27-IgD- B cells might portray an exhausted B cell phenotype resulting in lack of response to checkpoint inhibitor treatment in NSCLC

Background Checkpoint inhibitor (CI) therapy has revolutionized the therapy landscape of NSCLC. However, why some patients do not respond to CI therapy remains unknown. The correlation between intra-tumoral B cell follicles and response to CI therapy has been established. B cell follicles within the lymph node become more dispersed with age and CD27-IgD- B cells (DNBc) are described to be age-associated. Moreover, DNBc are abundant in chronic infection, elderly, long COVID and auto-immunity and are described to be anergic and exhausted and often lack expression of CD21. DNBc are expanded in NSCLC tumors compared to healthy lung tissue and inversely correlate to switched memory B cells in the tumor. In this study we explored if there is a correlation between this B cell subtype in peripheral blood of NSCLC patients and response to CI therapy. Methods Patients treated with CIs within the Erasmus Medical Center were included in a prospective observational immunomonitoring study. Nineteen NSCLC patients treated with either Pembrolizumab (Pem) or Nivolumab and 5 healthy controls (HC) were selected. Pem was given in 6/11 responding patients (R) and 5/8 non-responding patients (NR). Peripheral blood mononuclear cells (PBMC) were collected before start of treatment and characterized by multicolor flow cytometry. Results HC and R showed a similar pattern in most B cell subsets. NR had significantly lower proportion of B cells within the PBMC fraction than Rand HC (R: 7.14%, NR: 2.91%, HC: 10.60%). In addition, NR had a significantly higher frequency of DNBc than R and HC (R: 9.43%, NR: 23.78%, HC: 7.19%) and there was no correlation between age and DNBc. The frequency of DNBc correlated positively with lack of CD21 expression (r2: 0.83) and expression of Ki67 (r2: 0.54) both in NR, Rand HC. The frequency of Ki67+CD21-DNBc within the B cell fraction was higher in NR than in R and HC (NR: 18.34%, R: 3.51%, HC: 0.67%). Conclusions We are the first to describe that frequencies of DNBc are higher in NR compared to R and HC. Specifically, Ki67+CD21-DNBc are increased in NR and might reflect an anergic, exhausted B cell phenotype. The absence of a correlation between age and DNBc could suggest that the increase in DNBc is induced by the tumor. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure D. Dumoulin: Financial Interests, Personal, Other: Roche, BMS, MSD, AstraZeneca, Novartis. J.G. Aerts: Financial Interests, Personal, Research Grant: Amphera, Roche, Eli Lilly;Financial Interests, Personal, Advisory Board: Amphera, Bristol-Myers Squibb, Eli Lilly, MSD, Roche;Financial Interests, Personal, Ownership Interest: Amphera;Financial Interests, Personal, Other: Takeda. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Dutch oncology COVID-19 Consortium (DOCC): Outcome of COVID-19 in patients with cancer in a nationwide cohort study

Background: The coronavirus disease 2019 (COVID-19) pandemic is having significant impact on oncological care (Joode et al, Eur J Cancer 2020;136:132-139) and patients with cancer might have an increased risk for severe outcome of COVID-19. In order to identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods: This ongoing multicentre nationwide observational cohort study was designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a collaboration of oncology physicians in the Netherlands. A questionnaire was developed to collect pseudonymised patient data on patients’ characteristics, cancer diagnosis, cancer treatment, and outcome of COVID-19. All patients with COVID-19 and a cancer diagnosis or cancer treatment in the past 5 years were eligible for inclusion. Results: To date, > 600 cancer patients diagnosed with COVID-19 have been registered by 45 Dutch hospitals. Data of 442 registered patients with at least 4 weeks follow-up were cleaned and 351 patients could be included for the first analyses. The main cancer diagnoses were non-small cell lung cancer (13.4%), breast cancer (13.4%), and chronic lymphocytic leukaemia (8.8%). Overall, 114 (32.3%) out of 351 patients with cancer died from COVID-19. In multivariate analyses, age ≥ 65 years (p < 0.001), male gender (p = 0.035), prior or other malignancy (p = 0.045), and active diagnosis of haematological malignancy (p = 0.046) or lung cancer (p = 0.003) were independent risk factors for a fatal outcome of COVID-19. In a subgroup analysis of patients with active malignancy, the risk for a fatal outcome was mainly determined by tumour type (haematological malignancy or lung cancer) and age (≥ 65 years). Conclusions: The findings in this registry indicate that patients with a haematological malignancy or lung cancer have an increased risk of a worse outcome of COVID-19. During the ongoing COVID-19 pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, whereas treatment adjustments and prioritizing vaccination, when available, should also be considered. Legal entity responsible for the study: Erasmus Medical Center. Funding: Dutch Cancer Society. Disclosure: D.W. Dumoulin: Honoraria (self), Speakers fee: MSD;Honoraria (self), Speakers fee : Roche;Honoraria (self), Speakers fee: Astazeneca;Honoraria (self), Speakers fee: BMS;Honoraria (self), Speakers fee: Novartis;Honoraria (self), Speakers fee: Pfizer. H.M. Westgeest: Honoraria (self): Astellas;Honoraria (self): Roche;Travel/Accommodation/Expenses: Ipsen. L.E.L. Hendriks: Advisory/Consultancy, Mentorship program with key opinion leaders: funded by AstraZeneca: AstraZeneca;Honoraria (self), Educational webinars: Quadia;Research grant/Funding (institution): AstraZeneca;Advisory/Consultancy, Paid to institution: Eli Lilly;Advisory/Consultancy, Paid to institution: Roche Genentech;Advisory/Consultancy, Paid to institution: Pfizer;Advisory/Consultancy, Advisory board and speakers fee all paid to institution: MSD;Advisory/Consultancy, Paid to institution: Takeda;Leadership role, Local PI of pharma initiated research: AstraZeneca;Leadership role, Local PI of pharma initiated research: Novartis;Leadership role, Local PI of pharma initiated research: BMS;Leadership role, Local PI of pharma initiated research: MSD / Merck;Leadership role, Local PI of pharma initiated research: GSK;Leadership role, Local PI of pharma initiated research: Takeda;Leadership role, Local PI of pharma initiated research: Blueprint Medicines;Leadership role, Local PI of pharma initiated research: Roche Genentech;Advisory/Consultancy, Paid to institution: Amgen;Advisory/Consultancy, Paid to institution: Boehringer Ingelheim;Advisory/Consultancy, Paid to institution: BMS;Advisory/Consultancy, Travel/Accommodation/Expenses, Advisory board paid to institution: Roche Genentech;Travel/Accommodation/Expenses: BMS;Research grant/Funding (institution): Roche Genentech;R search grant/Funding (institution): Boehringer Ingelheim. A-M.C. Dingemans: Honoraria (self): Roche;Honoraria (self): Eli Lilly;Honoraria (self): Boehringer Ingelheim;Honoraria (self): Pfizer;Honoraria (self): BMS;Honoraria (self): Novartis;Honoraria (self): Takeda;Honoraria (self): PharmaMar;Advisory/Consultancy, non financial support: AbbVie;Research grant/Funding (institution): BMS;Research grant/Funding (institution): Amgen. A.A.M. Van der Veldt: Honoraria (institution), Advisory/Consultancy: BMS;Honoraria (institution), Advisory/Consultancy: MSD;Honoraria (institution), Advisory/Consultancy: Pfizer;Honoraria (institution), Advisory/Consultancy: Sanofi;Honoraria (institution), Advisory/Consultancy: Eisai;Honoraria (institution), Advisory/Consultancy: Ipsen;Honoraria (institution), Advisory/Consultancy: Roche;Honoraria (institution), Advisory/Consultancy: Novartis;Honoraria (institution), Advisory/Consultancy: Merck;Honoraria (institution), Advisory/Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.

Impact of the coronavirus disease 2019 pandemic on cancer treatment: the patients' perspective.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has inevitable consequences for medical care of patients without COVID-19. To assess the impact of this pandemic on oncological care, a nationwide survey was conducted among patients with cancer in the Netherlands. METHODS: The patients' perspective on oncological care was investigated using an online survey between March 29th 2020 and April 18th 2020. The survey consisted of 20 questions on four topics: patients' characteristics, contact with the hospital, consequences of the COVID-19 pandemic and concerns about COVID-19. RESULTS: Five thousand three hundred two patients with cancer completed this nationwide survey. Overall, 30% of patients reported consequences for their oncological treatment or follow-up. In the majority of cases, this resulted in conversion from hospital visit to consultation by phone or video. The most frequently adjusted treatments were chemotherapy (30%) and immunotherapy (32%). Among patients with delay and discontinuation of treatment, 55% and 63% of patients, respectively, were (very) concerned about these consequences of the COVID-19 pandemic. Consequences were independent of regional differences in COVID-19 incidence. However, patients in regions with high COVID-19 incidence were significantly more concerned. CONCLUSION: This is the first study investigating perspectives of patients with cancer during the COVID-19 pandemic. The study demonstrates the significant impact of the COVID-19 crisis on oncological care, indicating the need for psycho-oncological support during this pandemic.