Title : Durability of Response to SARS-CoV-2 BNT162b2 Vaccination in Patients on Active Anticancer Treatment
Abstract:
Abstract:
We recently reported initial findings from a prospective cohort study which evaluated the antispike (anti-S) IgG antibody response to the SARS-CoV-2 BNT162b2 messenger RNA (mRNA) vaccine (BioNTech/Pfizer) in patients with solid tumors on active anticancer treatment vs healthy controls.1 After a median of approximately 5.5 weeks from the second vaccine dose, 90% of the patients with cancer and 100% of the healthy controls were seropositive, and the median IgG titer in the patients was significantly lower than that in the controls:1931 (interquartile range [IQR], 509-4386) AU/mL vs 7160 (IQR, 3129-11241) AU/mL; P <.001.1
Herein, we describe the anti-S response in the patients with cancer vs the controls approximately 4 months after the second vaccine dose.
Methods
Study design, eligibility criteria, and anti-S IgG evaluation have been previously reported.1 The study was approved by the ethics committee of Rabin Medical Center. All participants provided written informed consent.
Statistical analyses were performed as previously described.1 A P value <.05 was considered significant. Statistical analysis was performed using R, version 4.0.2 (R Foundation).2
Results
The previous analysis included 102 patients with cancer and 78 controls.1 The current analysis included 95/102 patients (5 died, 2 withdrew) and 66/78 controls (12 withdrew). Baseline characteristics of the 95 patients and 66 controls are presented (Table).
After a median (IQR) of 123 (116-129) days from the second vaccination, 83 patients (87%) and all the controls (100%) were seropositive for anti-S IgG antibodies. The median titer in the patients was statistically significantly lower than in the controls (417 [IQR, 136-895] AU/mL vs 1220 [IQR, 588-1987] AU/mL; P <.001) (Table; Figure A). Evaluating the IgG titers by tumor type and anticancer treatment demonstrated a 3.6-fold range in median titer values across tumor types and a wider range (8.8-fold) across treatment types. The lowest titers were observed with immunotherapy plus chemotherapy/biological therapy (median [IQR], 94.4 [49.4-191]/147 [62.8-339]). In an exploratory multivariable analysis, the only variable significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy and immunotherapy plus biological therapy.
Of the 12 seronegative patients, 8 were seronegative in the previous analysis. One breast cancer patient who was seronegative in the previous analysis, was no longer on active therapy in the current analysis and became seropositive.
Evaluating the IgG titer as a function of the time between the second vaccine dose and the blood sample drawn from each patient demonstrated a significant negative linear correlation for the patients (R = -0.34, P<.005) and the controls (R = -0.7, P<.005) (Figure B,C).
Discussion
The seropositivity rate among the patients with cancer remained high (87%) approximately 4 months after the second BNT162b2 vaccination dose. The median IgG titer in the patients and the controls decreased over time. Notably, in both the previous1 and the current analysis, the IgG titers were statistically significantly lower in the patients vs the controls.
Data on the durability of protection after vaccination are limited for healthy subjects and lacking for oncological patients. Elevated antibody levels persisting 3 months after the second dose of mRNA-1273 vaccine (Moderna) were reported in 34 participants, although a slight decrease in antibody levels was reported.3 Interim results from a phase 3 trial of the mRNA-1273 vaccine in 33 healthy adults demonstrated that the antibody activity remained high in all age groups after approximately 7 months.4 Although the correlation between antibody levels after vaccination and clinical protection is yet to be proven, the accumulating evidence supports antibody response as a potential correlate of disease protection.5 Long-term cellular memory could call into question the need for a third BNT162b2 booster dose. Study limitations include lack of cellular immunity testing and/or neutralizing antibody testing.
Conflict of interest Disclosures: Dr. SM Stemmer received research grants
(to the institution) from CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelexis, Geicam, Halozyme, Incyte, Lilly, Moderna, Teva pharmaceuticals, and Roche, and owns stocks and options in CTG Pharma,
DocBoxMD, Tyrnovo, VYPE, Cytora, and CAN-FITE. The remaining authors declare no conflict of interest.
Funding/Support: No external funding.
Role of Funder/Sponsor: Not relevant.
Data sharing statement: The data sets generated during this study are available from the corresponding author upon request.
Additional Contributions: The authors thank the patients and their families and the nursing staff members at the Day Care Unit, Davidoff Caner Center, Rabin Medical Center. The authors also thank the Rabin Medical Center Biobank and Dr. Adva Levy-Barda for their support of this research. Lastly, the authors thank Avital Bareket-Samish, PhD, for medical editing support. She received financial compensation for her contribution.
