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

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 immunization (AEFI) to the BNT162b2 vaccine in patients on active treatment. Patients and methods Cancer patients candidate 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 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<1x10 9 /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< 1x10 9 /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.

Persistence of Anti-SARS-CoV-2 Antibodies in Long Term Care Residents Over Seven Months After Two COVID-19 Outbreaks

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Third dose of anti-SARS-CoV-2 vaccine for patients with cancer: Should humoral responses be monitored? A position article

“…Added to chemotherapy negative impact, some factors were found to be significantly associated with a lack of immunization ( 34 , 35 ): age, long-term corticosteroid treatment and lymphocyte count < 1 × 10 9 /L.…”

COVID-19 Vaccination in Patients With Malignancy; A Systematic Review and Meta-Analysis of the Efficacy and Safety

“…Both systemic and locoregional side-effects including fatigue, hypersensitivity reactions, fever, asthenia, vomiting, headaches, muscle and joint pain, chills, transient lymphadenopathy and injection site reactions (pain, erythema, itchiness, swelling, and redness) were reported. Although the various instruments and methods which were used for assessment of frequency, severity, and extend of the side-effects make it difficult to perform a meta-analysis investigation in this context, most of reported vaccines related side-effects were grade II, maximally ( 7 , 11 , 15 , 17 , 19 , 20 , 22 , 24 , 28 , 32 , 35 – 37 ).…”