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


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

In This Article

Abstract and Introduction


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%) (P = .02). Titers were also statistically significantly different among treatment types (P = .002).

Conclusions: The BNT162b2 vaccine is safe and effective in actively treated patients with cancer. The relatively lower antibody titers and lower proportion of seropositive patients, especially among chemotherapy-treated patients, call for continuing the use of personal protective measures in these patients, even following vaccination.


Patients with cancer are at increased risk for morbidity and mortality from COVID-19,[1] and active treatment may further increase these risks.[2] Yet, patients with cancer were excluded from the pivotal trials of the COVID-19 vaccines,[3–5] and the safety and efficacy of the vaccine in this large and vulnerable population are currently unknown. Despite a lack of data, current guidelines of both the American Society for Clinical Oncology and the European Society for Medical Oncology strongly support vaccination of patients with cancer treated with systemic anticancer therapy.[6,7]

On December 19, 2020, the Israeli Ministry of Health launched a national mass vaccination campaign, aiming at rapid vaccination of the entire adult Israeli population. All Israeli citizens aged 16 years or older who were not previously infected with SARS-CoV-2 were eligible for the mRNA BNT162b2 vaccine. Vaccines were readily available, free of charge, and administered as recommended by the manufacturer at a 21-day interval. The second dose was omitted if the patient contracted SARS-CoV-2 infection following the first dose. By April 30, 2021, 5 048 333 Israelis (55.8% of the Israeli population) were already fully vaccinated. Although data were lacking, the Israeli Ministry of Health not only recommended vaccination of all patients with cancer but also prioritized them to be vaccinated at the early stages of the campaign, regardless of disease stage, performance status, or life expectancy.

Accumulating data indicate that the BNT162b2 vaccine is indeed safe in actively treated cancer patients. We have recently reported on the short-term safety of 2 doses of the BNT162b2 vaccine in 134 patients with a variety of solid cancers treated with immune checkpoint inhibitors (ICI),[8] and Monin et al.[9] reported on the safety of the vaccine in a cohort of 151 patients, of whom 95 had solid cancers and 25 received 2 doses. No unexpected or severe side effects were noted in both studies. Similarly, the vaccine was also found to be safe among patients with chronic lymphocytic leukemia (CLL).[10] Although data regarding safety are accumulating and reassuring, data regarding activity of the BNT162b2 vaccine are lacking. Direct assessment of the ability of the BNT162b2 vaccine to reduce morbidity and mortality among patients with cancer is limited because of the small number of cancer patients relative to the general population and because of the presence of major confounding factors, including social distancing and the low prevalence of SARS-CoV-2 infection in the general population following mass vaccination. Indeed, a cohort of nearly 600 000 individuals was required to determine the efficacy of the BNT162b2 vaccine at the national level.[11] To overcome this obstacle, several surrogate markers for the activity of the vaccine are being used; the most common is a direct measurement of anti-SARS-Cov-2 spike (S) antibody titers in the serum. Recent studies used this test and reported on antigenicity and seroconversion in patients with malignant diseases. A recent study from our institution noted an antibody response in only 40% of 167 patients with CLL receiving 2 doses of the BNT162b2 vaccine,[10] and low responses were also noted in a cohort of 29 multiple myeloma patients.[12] Response to this vaccine in patients with solid cancers was evaluated in 2 small cohorts.[9,13] Although both studies reported on approximately 95% immunogenicity following the second vaccine dose, no association with either tumor or treatment type could be determined in either of these studies because of the small number of patients. We describe here safety and antibody response following administration of the second dose of the BNT162b2 vaccine in a cohort of 326 actively treated patients with solid tumors.