key: cord-0763372-nzz8s0lc
authors: Salgia, S. K.; Malhotra, J.; Zengin, Z.; Meza, L.; Ely, J.; Hsu, J.; Kelley, E.; Chehrazi-Raffle, A.; Govindarajan, A.; Muddasani, R.; Salgia, N.; Dizman, N.; Chawla, N.; Dorff, T.; Lyou, Y.; Karczewska, E.; Trent, J.; Salgia, R.; Altin, J.; Pal, S. K.
title: 1564MO Characterization of COVID-19 vaccination response by antibody (Ab) titer and T-cell receptor (TCR) sequencing in patients (pts) with advanced genitourinary (GU) cancers
date: 2021-09-30
journal: Annals of Oncology
DOI: 10.1016/j.annonc.2021.08.1557
sha: 4f30484f81ef4b82b1e43394c3e4cd74682254f4
doc_id: 763372
cord_uid: nzz8s0lc

Background: Preliminary studies have characterized potential adverse effects associated with COVID-19 vaccination in pts with cancer. However, biological characterization of vaccine response has yet to be performed. Methods: Eligible pts with advanced GU cancers (metastatic/unresectable prostate, bladder and renal cell carcinoma [RCC]) and had not yet received COVID-19 vaccination. Pts were consented to receive sequential blood draws prior to vaccination and at landmarks of 2, 6, and 12 mos following vaccination. Pts on systemic treatment had additional blood draws coinciding with their first 3 cycles of therapy following vaccination. Ab titers to SARS-CoV-2 were quantified via ELISA and reported as an immune status ratio (ISR). RNA was extracted from PBMC aliquots, converted into cDNA and TCR α/β sequences were selectively amplified. TCR abundance and homology clustering was performed using custom scripts. Results: As of May 14, 2021, 130 pts had consented to the study of whom 126 pts submitted baseline (BL) specimens. The current analysis focuses on 56 pts who submitted cycle 1 (C1) specimens. Among these, 29, 26, and 1 pts had RCC, prostate and bladder cancer, respectively;19 were on checkpoint inhibitor (CPI)-based regimens while 37 were on non-CPI regimens. BNT162b2 (Pfizer) was the most commonly administered vaccine in the cohort (n=29), followed by mRNA-1273 (Moderna;n=26). COVID-19 Ab titers increased significantly from BL to C1 across the cohort from 0.19 (interquartile range [IQR] 0.12-0.18) to 4.37 (IQR 0.2-6.60;P<0.0001). However, 8/56 pts (14.3%) receiving CPI-based regimens and 8/56 pts (14.3%) receiving non-CPI-based regimens were noted to have negative Ab titers after a median of 18 and 35 days following initial vaccination, respectively. No significant difference was observed in the increase from BL to C1 in pts receiving CPI vs non-CPI-based regimens. Specimen collection is ongoing;updated Ab titer data and TCR sequencing data will be presented. Conclusions: Our data prompt concern for delayed or insufficient COVID-19 Ab response in a subset of pts with advanced GU cancers. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: R. Salgia: Non-Financial Interests, Personal, Advisory Board: Janssen;Non-Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Advisory Board: Merck;Non-Financial Interests, Personal, Advisory Board: Novartis. S.K. Pal: Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: Medivation;Financial Interests, Personal, Invited Speaker: Astellas Pharma;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Aveo;Financial Interests, Personal, Advisory Board: Myriad;Non-Financial Interests, Personal, Other: Genentech;Non-Financial Interests, Personal, Other: Exelixis;Non-Financial Interests, Personal, Other: BMS;Non-Financial Interests, Personal, Other: Astellas Pharma;Financial Interests, Institutional, Funding: Medivation. All other authors have declared no conflicts of interest.

Characterization of COVID-19 vaccination response by antibody (Ab) titer and T-cell receptor (TCR) sequencing in patients (pts) with advanced genitourinary (GU) cancers S.K. Salgia 1 , J. Malhotra 1 , Z. Zengin 1 , L. Meza 1 , J. Ely 2 , J. Hsu 1 Background: Preliminary studies have characterized potential adverse effects associated with COVID-19 vaccination in pts with cancer. However, biological characterization of vaccine response has yet to be performed.

Methods: Eligible pts with advanced GU cancers (metastatic/unresectable prostate, bladder and renal cell carcinoma [RCC]) and had not yet received COVID-19 vaccination. Pts were consented to receive sequential blood draws prior to vaccination and at landmarks of 2, 6, and 12 mos following vaccination. Pts on systemic treatment had additional blood draws coinciding with their first 3 cycles of therapy following vaccination. Ab titers to SARS-CoV-2 were quantified via ELISA and reported as an immune status ratio (ISR). RNA was extracted from PBMC aliquots, converted into cDNA and TCR a/b sequences were selectively amplified. TCR abundance and homology clustering was performed using custom scripts.

Results: As of May 14, 2021, 130 pts had consented to the study of whom 126 pts submitted baseline (BL) specimens. The current analysis focuses on 56 pts who submitted cycle 1 (C1) specimens. Among these, 29, 26, and 1 pts had RCC, prostate and bladder cancer, respectively; 19 were on checkpoint inhibitor (CPI)-based regimens while 37 were on non-CPI regimens. BNT162b2 (Pfizer) was the most commonly administered vaccine in the cohort (n¼29), followed by mRNA-1273 (Moderna; n¼26). COVID-19 Ab titers increased significantly from BL to C1 across the cohort from 0.19 (interquartile range [IQR] 0.12-0.18) to 4.37 (IQR 0.2-6.60; P<0.0001). However, 8/56 pts (14.3%) receiving CPI-based regimens and 8/56 pts (14.3%) receiving non-CPI-based regimens were noted to have negative Ab titers after a median of 18 and 35 days following initial vaccination, respectively. No significant difference was observed in the increase from BL to C1 in pts receiving CPI vs non-CPIbased regimens. Specimen collection is ongoing; updated Ab titer data and TCR sequencing data will be presented.

Conclusions: Our data prompt concern for delayed or insufficient COVID-19 Ab response in a subset of pts with advanced GU cancers.

Legal entity responsible for the study: The authors. 

Time-dependent improvement in the clinical outcomes from COVID-19 in cancer patients: An updated analysis of the OnCovid registry

Surgery and Cancer, Imperial College London -Hammersmith Hospital

Early reports from registry studies demonstrated high vulnerability of cancer patients from COVID-19, with case-fatality rates (CFR) >30% at the onset of the pandemic. With advances in disease management and increased testing capacity, the lethality of COVID-19 in cancer patients may have improved over time. Methods: The OnCovid registry lists European cancer patients consecutively diagnosed with COVID-19 in 35 centres from

At data cut-off, the 2634 eligible patients demonstrated significant timedependant improvement in 14-days CFR with trimestral estimates of 29.8%, 20.3%, 12.5%, 17.2% and 14.5% (p<0.0001)

4% vs 33.9%, p<0.001), requiring hospitalization (59.8% vs 42.1%, p<0.001) and anti-COVID-19 therapy (61.7% vs 49.7%, p<0.001). The 14-days CFR for the 1st and 2nd semester was 25.6% vs 16.2% (p<0.0001), respectively. After adjusting for gender, age, comorbidities, tumour features, COVID-19 and anti-cancer therapy and COVID-19 complications, patients diagnosed in the 1st semester had an increased risk of death at 14 days

Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding

Financial Interests, Personal, Speaker's Bureau: ViiV Healthcare; Financial Interests, Personal, Speaker's Bureau: Bayer; Financial Interests

Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest

Surgery is the main modality of cure for solid cancers and was prioritised to continue even during SARS-CoV-2 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during COVID-19