Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine Among Actively Treated Cancer Patients

Hagai Ligumsky, MD, PhD; Esraa Safadi, BSc; Tal Etan, MD; Noam Vaknin, BSc; Manuel Waller, MA; Assaf Croll, BSc; Alla Nikolaevski-Berlin, PhD; Inbal Greenberg, MSc; Tami Halperin, PhD; Asaf Wasserman, MD; Lior Galazan, BSc; Nadir Arber, MD; Ido Wolf, MD

Disclosures

J Natl Cancer Inst. 2022;114(2):203-209.

Abstract and Introduction

Abstract

Background: Activity and safety of the SARS-CoV-2 BNT162b2 vaccine in actively treated patients with solid tumors is currently unknown.

Methods: We conducted a retrospective study of 326 patients with solid tumors treated with anticancer medications to determine the proportion of cancer patients with immunogenicity against SARS-CoV-2 following 2 doses of the BNT162b2 vaccine. The control group comprised 164 vaccinated healthy adults. Anti-SARS-CoV-2 S immunoglobulin G antibodies were measured using a level greater than 50 AU/mL as a cutoff for seropositivity. Information on adverse effects was collected using a questionnaire. All statistical tests were 2-sided.

Results: Most patients (205, 62.9%) were treated with chemotherapy either alone or with additional therapy; 55 (16.9%) were treated with immune checkpoint inhibitors and 38 (11.7%) with targeted therapy alone; 28 (8.6%) received other combinations. The vaccine was well tolerated, and no severe side effects were reported. Among patients with cancer, 39 (11.9%) were seronegative compared with 5 (3.0%) of the control group (P = .001). Median immunoglobulin G titers were statistically significantly lower among patients with cancer compared with control (931 AU/mL vs 2817 AU/mL, P= .003). Seronegativity proportions were higher in the chemotherapy-treated group (n = 19; 18.8%) compared with the immune checkpoint inhibitor–treated patients (n = 5; 9.1%) and with those treated with targeted therapy (n = 1; 2.6%) (

Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Clinical characteristics of study participants
Characteristics	Cancer patients (N = 326)	Healthy controls (N = 164)	P
Median age, y (range)	66 (29–89)	54 (24–90)	<.001^a
Female, No. (%)	203 (62.3)	100 (60.9)	.78^b
Days from 2nd dose to COVID-19 Ab test, median (range)	78 (21–115)	72 (21–115)	.08^a
Cancer type, No. (%)
Gastrointestinal	84 (25.8)	NA
Breast	82 (25.2)	NA
NSCLC	45 (13.8)	NA
Gynecological	41 (12.6)	NA
Genitourinary	29 (8.9)	NA
Skin cancers including melanoma	13 (4.0)	NA
CNS	12 (3.7)	NA
Sarcoma	10 (3.1)	NA
Head and neck	7 (2.1)	NA
Other	3 (0.9)	NA
Cancer stage, No. (%)
Local	96 (29.4)	NA
Metastatic	230 (70.6)	NA

^a P values derived from the nonparametric Mann-Whitney U test, 2-sided. Ab = antibody; CNS = central nervous system; NA = not applicable; NSCLC = non-small cell lung cancer.
^b P values derived from the parametric χ², 2-sided.

Table 2. Immunogenicity in patients with cancer compared with healthy controls
Variables	Cancer patients (N = 326)	Healthy controls (N = 164)	P
Median IgG Ab titer (range), AU/mL	931 (0–40 000)	2817 (0–40 000)	.003^a
Seronegative (<50 AU/mL), No. (%)	39 (11.9)	5 (3.0)	.001^b
IgG titer (AU/mL) by range, No. (%)
50–100	21 (6.4)	0 (0.0)	.001^b
101–1000	114 (35.0)	31 (18.9)
1001–5000	106 (32.5)	74 (45.1)
5001–10 000	24 (7.4)	33 (20.1)
<10 001	22 (6.7)	21 (12.9)

^a P values derived from the nonparametric Mann-Whitney U test, 2-sided. Comparison of median IgG Ab between cancer patients and control group was adjusted for age and sex using a logistic regression model including these variables. Ab = antibody; IgG = immunoglobulin G.
^b P values derived from the parametric χ², 2-sided.

Table 3. Comparison between cancer patients with either seropositive or seronegative response to the BNT162b2 vaccine
Variables	SARS-CoV-2 S IgG seropositive (n = 287)	SARS-CoV-2 S IgG seronegative (n = 39)	P
Median age (range), y	66 (22–91)	67 (35–89)	.25^a
Female, No. (%)	174 (60.6)	29 (74.4)	.10^b
Metastatic disease, No. (%)	205 (71.4)	25 (64.1)	.74^b
Median days from 2nd vaccination to COVID-19 Ab test	76 (23–115)	76 (2–99)	.47^a
Chemotherapy-based treatment, No. (%)	176 (61.3)	29 (74.4)	.12^b
Cancer type, No. (%)			.21^c
Gastrointestinal	78 (27.2)	6 (15.4)
Breast cancer	68 (23.7)	14 (35.9)
NSCLC	40 (13.9)	5 (12.8)
Gynecological	39 (13.6)	2 (5.1)
Genitourinary	24 (8.4)	5 (12.8)
Other	38 (13.2)	7 (17.9)
COVID-19 infection, No.	0	0	>.99

^a P values derived from the nonparametric Mann-Whitney U test, 2-sided. Ab = antibody; IgG = immunoglobulin G; NSCLC = non-small cell lung cancer.
^b P values derived from the parametric χ² test, 2-sided.
^c P value derived from χ² test, 2-sided.

Table 4. Immunogenicity of BNT162b2 vaccine by treatment type
Variables	Chemotherapy (n = 101)	ICI (n = 55) (n = 38)	Targeted therapy	P
Median age (range), y	67 (22–84)	69 (27–91)	63 (33–85)	.01^a
Female, No. (%)	67 (66.3)	21 (38.2)	29 (76.3)	<.001^b
Metastatic disease, No. (%)	63 (62.4)	39 (70.9)	26 (68.4)	.52^b
Cancer diagnosis, No. (%)				.002^b
Gastrointestinal	36 (35.6)	7 (12.7)	3 (7.9)
Breast cancer	27 (26.7)	0 (0.0)	13 (34.2)
NSCLC	5 (5.0)	20 (36.4)	2 (5.3)
Other	33 (32.7)	28 (50.9)	20 (52.6)
Median IgG titer (range), AU/mL	578 (0–28 229)	793 (2–12 658)	1895 (46–40 000)	.002^a
Seronegative <50 IU, No. (%)	19 (18.8)	5 (9.1)	1 (2.6)	.02^b

^a P values derived from the nonparametric Kruskal-Wallis test, 2-sided. Ab = antibody; ICI = immune checkpoint inhibitors; IgG = immunoglobulin G; NSCLC = non-small cell lung cancer.
^b P values derived from the parametric χ² test, 2-sided.