Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment

Tania Buttiron Webber, Nicoletta Provinciali, Marco Musso, Martina Ugolini, Monica Boitano, Matteo Clavarezza, Mauro D'Amico, Carlotta Defferrari, Alberto Gozza, Irene Maria Briata, Monica Magnani, Fortuna Paciolla, Nadia Menghini, Emanuela Marcenaro, Raffaele De Palma, Nicoletta Sacchi, Leonello Innocenti, Giacomo Siri, Oriana D'Ecclesiis, Isabella Cevasco, Sara Gandini, Andrea DeCensi, Tania Buttiron Webber, Nicoletta Provinciali, Marco Musso, Martina Ugolini, Monica Boitano, Matteo Clavarezza, Mauro D'Amico, Carlotta Defferrari, Alberto Gozza, Irene Maria Briata, Monica Magnani, Fortuna Paciolla, Nadia Menghini, Emanuela Marcenaro, Raffaele De Palma, Nicoletta Sacchi, Leonello Innocenti, Giacomo Siri, Oriana D'Ecclesiis, Isabella Cevasco, Sara Gandini, Andrea DeCensi

Abstract

Purpose: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment.

Patients and methods: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose.

Results: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 109/L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009).

Conclusion: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 109/L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS.

Gov identifier: NCT04932863.

Keywords: Antibody responses to the BNT162b2 vaccine; COVID-19 vaccine in cancer patients; Cancer biological treatment; Cancer chemotherapy; Cancer hormone therapy; Cancer immunotherapy; Cancer target therapy; Immunogenicity; SARS-CoV-2 vaccine; SARS-CoV-2 vaccine adverse effects.

Conflict of interest statement

Conflict of interest statement We declare no competing interests.

Copyright © 2021. Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
Participant flow diagram.
Fig. 2
Fig. 2
Forest plot of the relative risk (RR) of poor seroconversion (

Fig. 3

Forest plot of the Odds…

Fig. 3

Forest plot of the Odds Ratios (OR) for adverse events following immunisation from…

Fig. 3
Forest plot of the Odds Ratios (OR) for adverse events following immunisation from a multivariable logistic model adjusted for sex, age and smoke.
Fig. 3
Fig. 3
Forest plot of the Odds Ratios (OR) for adverse events following immunisation from a multivariable logistic model adjusted for sex, age and smoke.

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