ABSTRACT
Background: Short-term effectiveness of COVID-19 vaccination is widely demonstrated, but the emerging real-world data suggest that immunity may wane over-time (Levin et al. NEJM 2021). Herein we aimed to explore the long-term efficacy of the COVID-19 vaccination among pts with genitourinary cancer. Methods: In this study, pts with genitourinary malignancies (prostate, kidney, and bladder cancers) who had not received COVID-19 vaccination were included. Blood samples were collected prior to and after one dose of either an adenovirus- or mRNA-based COVID-19 vaccine at the 2- and 6-month timepoints. Additional blood samples from pts receiving systemic treatment were collected at 3 consecutive therapy cycles following vaccination. Antibody titers were assessed using the SCoV-2 Detect IgG ELISA assay and results were reported as immune status ratios (ISR). T-cell receptor (TCR) repertoire sequencing was performed using the MiXCR software (MiLabs) and custom strips were used to assess TCR abundance and homology clustering. Results: A total of 183 pts were enrolled, and 136 pts provided baseline blood samples. Among these, 59 (8:51 F:M) provided samples for both the 2-and 6-month timepoints by the 10/6/2021 data cut-off. In this subset of pts, median age was 66 (range 48-85) and 33 (55.9%), 25 (42.4%), and 1 (1.7%) pts had prostate, kidney, and bladder cancer, respectively. A majority of the pts (93.2%) were on systemic treatment with 23.7% on immune checkpoint inhibitors, 18.6% on targeted agents, and 1.7% on chemotherapy. The most commonly administered vaccines were BNT162b2 (61.0%) followed by mRNA-1273 (37.3%) and Ad26.COV2.S (1.7%). The mean (±standard deviation) ISR values at baseline and 2 months were 0.68±1.59 and 6.62±1.75, respectively. At the 6-month timepoint, mean ISR was 5.46±1.61;this was significantly lower than the 2-month antibody titers (p < 0.0001), and reflects a reduction of 17.6%. Further data on TCR sequencing will be presented at the meeting. Conclusions: To our knowledge, this is the first data assessing the long-term serologic outcomes of COVID-19 vaccination in pts with cancer. Our data suggest waning immunity over time in cancer pts. Strategies to prolong host immunity against SARS COV-2 (e.g., booster vaccination) are likely warranted.
ABSTRACT
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.