Analysis of the humoral and cellular immune response after a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors with or without chemotherapy: an update after 6 months of follow-up

Abstract

Background The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti PD-1/PD-L1 with or without chemotherapy six months after BNT162b2 vaccine. Patients and methods In the previous study, 88 patients were enrolled, while the analyses below refer to the 60 patients still on immunotherapy at the time of the follow up. According to previous SARS-CoV-2 exposure, patients were classified in SARS-CoV-2 naïve (without previous SARS-CoV-2 exposure) and SARS-CoV-2 experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Abs) titer against B.1.1 strain and total anti-Spike IgG concentration were quantified in serum samples. ELISpot assay was used for quantification of anti-Spike interferon gamma (IFNγ) producing cells/10 6 peripheral blood mononuclear cells (PBMC). Fifty patients (83.0%) were on immunotherapy alone, while ten patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. Results Median T-cell response at six months was significantly lower than that measured at three weeks after vaccination (50 interquartile range (IQR) 20-118.8 vs 175IQR 67.5-371.3 IFNγ producing cells/10 6 PBMC;p<0.0001). The median reduction of IgG concentration was 88% in SARS-CoV-2 naïve subject, 2.1% in SARS-CoV-2 experienced subjects. SARS-CoV-2 NT Abs titer was stable maintained in SARS-CoV-2 experienced subjects while a significant decrease was observed in SARS-CoV-2 naïve subjects (from median 1:160 IQR 1:40-1:640 to median 1:20 IQR 1:10-1:40;p<0.0001). A weak correlation was observed between SARS-CoV-2 NT Abs and Spike-specific IFNγ producing cells at both six months and three weeks after vaccination (r=0.467;p=0.0002 and r=0.428;p=0.0006,respectively). Conclusions Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2 naïve subjects. Our data support administering third dose of COVID-19 vaccine to cancer patients treated with PD1/PD-L1 inhibitors.

Immunogenicity and safety after the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors on active treatment: a prospective cohort study

“…According to our previous paper [11], we have defined "SARS-CoV-2 experienced" those patients with a documented past positive SARS-CoV-2 RNA in nasopharyngeal swab and/or positive anti-Spike IgG before the first dose of vaccination, otherwise, they were classified as "SARS-CoV-2 naïve". The primary endpoint was to assess the increase of IgG antibody level between the baseline and 3 weeks after the third dose of BNT162b2 SARS-CoV-2 vaccine.…”

“…Briefly, 50 µl of serum in serial fourfold dilution were added in two wells of a flat bottom tissue culture microtiter plate (COSTAR, Corning Incorporated, NY 14831, USA). The same volume of 100 TCID50 of SARS-CoV-2 strain was added and plates were incubated at 33°C in 5% CO2, according to our local protocol [11]. After 1 hour incubation at 33°C 5% CO2, VERO E6 cells were added to each well.…”

Six-month humoral and cellular immune response to the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors: a longitudinal cohort study with a focus on the variants of concern

“…According to our protocol [14], the quantitative characterization of spike-specific IgG antibodies was carried out by Trimeric assay (Liaison, Diasorin, Saluggia, Italy) and results were given as BAU/ml (positive results >33.8 BAU/ml). Additionally, the neutralizing antibody (NT Ab) titers against the B.1.1, B.1.617.2 and BA.1 strains were measured as previously reported [16][17][18] and results were given as positive when NT Ab was ≥ 1:10.…”

Brief Research Report: Anti-SARS-CoV-2 Immunity in Long Lasting Responders to Cancer Immunotherapy Through mRNA-Based COVID-19 Vaccination

“…However, vaccine immunogenicity in immunocompromised individuals is expected to be diminished to various degrees depending on the particular condition and state of immunosuppression ( 2 , 14 – 17 ). Here we report vaccination outcomes in a small cohort of solid CPs including a cohort of long survivors under immunotherapy (cohort B, subgroup B.1) with checkpoint inhibitors (mainly anti PD-1/PD-L1 antibodies) and relate them to COVID-19 vaccine studies of cancer patients that have been published until January 2022 ( 3 , 14 , 16 , 18 – 28 ).…”

“…Here we report vaccination outcomes in a small cohort of solid CPs including a cohort of long survivors under immunotherapy (cohort B, subgroup B.1) with checkpoint inhibitors (mainly anti PD-1/PD-L1 antibodies) and relate them to COVID-19 vaccine studies of cancer patients that have been published until January 2022 (3,14,16,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”