Impact of chemotherapy and/or immunotherapy on neutralizing antibody response to SARS‐CoV‐2 mRNA‐1237 vaccine in patients with solid tumors

Abstract

Patients with solid tumors have been a risk group since the beginning of the SARS‐CoV‐2 pandemic due to more significant complications, hospitalizations or deaths. The immunosuppressive state of cancer treatments or the tumor itself could influence the development of post‐vaccination antibodies. This study prospectively analyzed 89 patients under chemotherapy and/or immunotherapy, who received two doses of the mRNA‐1237 vaccine, and were compared with a group of 26 non‐cancer individuals. Information on adverse events and neutralizing antibodies against the ancestral strain of SARS‐CoV‐2 (WH1) have been analyzed. Local reactions accounted for 65%, while systemic reactions accounted for 46% of oncologic individuals/cancer patients. Regarding the response to vaccination, 6.7% of cancer patients developed low neutralizing antibody levels. Lower levels of neutralizing antibodies between cancer and non‐cancer groups were significant in individuals without previous SARS‐CoV‐2 infection, but not in previously infected individuals. We also observed that patients receiving chemotherapy or chemoimmunotherapy have significantly lower levels of neutralizing antibodies than non‐cancer individuals. In conclusion, our study confirms the importance of prioritizing cancer patients receiving anticancer treatment in SARS‐CoV‐2 vaccination programs.

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients

“…Patients with solid tumor malignancies had much stronger immune responses than those with HMs (likely due to B-cell defects [22,23]) 4 weeks after the third dose; however, this statistical difference was lost at 6 months, results that are similar to those published for other mRNA vaccines [24]. Neutralizing antibody responses at 28 days post-dose 3 were reduced in patients who had lower lymphocyte counts (≤1 × 10 9 /L) and those who had received anticancer therapies in the last 3 months, particularly those that received BTK inhibitors, small molecules, anti-CD20 antibodies, and anti-CD38 antibodies (results also noted in other studies) [25][26][27][28]. Most importantly, we observed increased neutralization GMTs, regardless of cancer type or treatment, even in patients that were seronegative prior to dose 3 (similar to the total antibody GMT increase previously described [18]), and at 6 months following the receipt of the third vaccine dose, those titers were still at least 10-fold greater than those recorded prior to dose 3.…”

PD-1/PD-L1 blockade restores tumor-induced COVID-19 vaccine bluntness

“…To date, the effects of PD-1/PD-L1 ICB therapy on COVID-19 vaccine response of cancer patients have been reported in several clinical studies, albeit with debatable conclusions. On the one hand, comparable antibody responses against COVID-19 vaccination were observed between cancer patients with PD-1/PD-L1 ICB therapy and healthy participates [44] , [45] , which hints the restoration of tumor-blunted COVID-19 vaccine effectiveness in patients receiving PD-1/PD-L1 ICB therapy to that of healthy participates. Indeed, cancer patients with PD-1/PD-L1 ICB therapy showed a trend towards increased COVID-19 vaccine effectiveness as compared to that of cancer patients with no therapies [5] , [46] .…”

Global seroprevalence of neutralizing antibodies against adeno-associated virus serotypes used for human gene therapies

“…Several recent studies suggest that patients with cancer may exhibit lower prevalence of NAbs in response to vaccination or virus exposure. 70 , 71 , 72 Therefore, it is possible that the results of this study may underestimate the prevalence of NAbs in the general population. While some cancer treatments are immunomodulatory, we did not observe a difference in the prevalence of NAb positivity between those exposed to immunomodulatory drugs and those not exposed.…”