COVID-19 vaccines in adult cancer patients with solid tumours undergoing active treatment: Seropositivity and safety. A prospective observational study in Italy

Abstract

Introduction Cancer patients are presumed a frail group at high risk of contracting coronavirus disease (COVID-19), and vaccination represents a cornerstone in addressing the COVID-19 pandemic. However, data on COVID-19 vaccination in cancer patients are fragmentary and poor. Methods An observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or mRNA-1273 vaccine in adult patients with solid cancer undergoing active anticancer treatment or whose treatment had been terminated within 6 months of the start of study. The control group was composed of healthy volunteers. Serum samples were evaluated for SARS-COV-2 antibodies prior vaccinations and 2-6 weeks after the administration of the second vaccine dose. Primary endpoint: seropositivity rate. Secondary endpoints: safety, factors influencing seroconversion, IgG titers of patients versus healthy volunteers, COVID-19 infection. Results Between 20 March 2021 and 12 June 2021, 293 consecutive cancer patients with solid tumors underwent a program of COVID-19 vaccinations: of these, 2 patients refused vaccination, 13 did not receive the second dose of the vaccine due to cancer progression and 21 had COVID-19 antibodies at baseline and were excluded. The 257 evaluable patients had a median age of 65 years (range 28-86), 66.15% with metastatic disease. Primary endpoint: seropositivity rate in patients was 75.88%, versus 100% in the control group. Secondary endpoints: no grade 3-4 side effects, no COVID-19 infections were reported. Patients median IgG titer was significantly lower than in the control group, male sex and active anticancer therapy influenced negatively seroconversion. BNT162b2 or mRNA-1273 vaccines were immunogenic in cancer patients, showing good safety profile.

Impaired seroconversion after SARS-CoV-2 mRNA vaccines in patients with solid tumours receiving anticancer treatment

“…In accordance with previous studies 14 , 15 , 16 , 20 , 21 , 26 , 27 , our data in this specific population demonstrate a lower probability to obtain seroconversion after a complete course of SARS-CoV-2 mRNA vaccination. About 6% of cancer patients in treatment failed to develop an immune response after mRNA vaccination, as compared to only 0.2% in controls, accounting for a 30-fold higher probability.…”

“…As the spike-protein (S) retains a pivotal role in viral infection and pathogenesis of COVID-19, novel messenger ribonucleic acid (mRNA) vaccines (BNT162b2 by Pfizer/BioNTech, and mRNA-1273 by Moderna) were found able to induce adequate anti-S response in healthy patients, obtaining more than 90% efficacy in preventing a severe course of COVID-19 12 , 13 . Despite these promising results, cancer patients were mostly excluded from clinical trials, and their ability of seroconversion is now the main issue of a growing number of studies 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 . However, some of these studies assessed heterogeneous populations including both solid tumours and hematological malignancies.…”

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

“…This strategy is supported by several studies focused on the durability of vaccine-induced antibodies (Abs) levels and clinical studies conducted in the general population, as well ( 1 , 2 , 3 , 4 , 5 ). Nevertheless, to date, there are no recommendations allowing for a personalized prescription dedicated to immunocompromised people, including patients with cancer displaying lower anti-SARS-CoV-2 vaccine immune responses ( 6 , 7 , 8 , 9 , 10 ). Another issue is still unresolved, and it concerns the exact timing of the earlier waning immunity observed at post-vaccination in immunocompromised patients, such as patients with cancer undergoing immunosuppressive therapy.…”

“…The main data concerning humoral vaccine responses in solid cancer or HM patients can be summarized as follows: Low seroconversion rate after the first vaccine dose (D1) ( 6 , 7 , 8 , 9 , 10 ); Conversely, an overall high seroconversion rate in solid oncology patients after the second dose (D2), with more than 80-90% of them having developed anti-Spike (S) Abs ( 6 , 7 , 8 , 9 , 10 , 27 , 28 , 29 ); Lower median anti-S Abs levels compared with healthy control (HC) group, consisting of highly heterogeneous responses with patients classified from low-responders to high-responders, the latter displaying a similar humoral response than HC group ( 6 , 7 , 8 , 9 , 10 , 27 , 28 , 29 ); A much lower seroconversion rate in patients with HM ( 30 , 31 , 32 ), especially those exhibiting chronic lymphoid leukemia (CLL), even when left untreated ( 31 ), as well as patients with multiple myeloma and those with additional deleterious prognostic factors, including age ( 31 ); The poorest vaccine response rate was recorded in patients undergoing anti-CD20 therapy or having stopped it for less than 12 months, with virtually no humoral response at all after a full two-dose vaccination ( 32 , 33 ). …”

“…Conversely, an overall high seroconversion rate in solid oncology patients after the second dose (D2), with more than 80-90% of them having developed anti-Spike (S) Abs ( 6 , 7 , 8 , 9 , 10 , 27 , 28 , 29 );…”