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

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

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.