Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial

Abstract

Background: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering 'booster' doses of COVID-19 vaccines beyond the standard 2-dose series, for this group of patients. Therefore, studying the efficacy of these additional vaccine doses against SARS-CoV-2 and variants of concern is of utmost importance in this immunocompromised patient population.Methods: We conducted a prospective single arm clinical trial enrolling patients with cancer that had received two doses of mRNA or one dose of AD26.CoV2.S vaccine and administered a 3rd dose of mRNA vaccine. We further enrolled patients that had no or low responses to three mRNA COVID vaccines and assessed the efficacy of a 4th dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity and neutralization activity were again assessed at baseline and 4 weeks.Results: We demonstrate that a 3rd dose of COVID-19 vaccine leads to seroconversion in 57% of patients that were seronegative after primary vaccination series. The immune response is durable as assessed by anti-S antibody titers, T-cell activity and neutralization activity against wild-type SARS-CoV2 and BA1.1.529 at 6 months of follow up. A subset of severely immunocompromised hematologic malignancy patients that were unable to mount an adequate immune response (titer <1000 AU/mL) after the 3rd dose and were treated with a 4th dose in a prospective clinical trial which led to adequate immune-boost in 67% of patients. Low baseline IgM levels and CD19 counts were associated with inadequate seroconversion. Booster doses induced limited neutralization activity against the Omicron variant.Conclusions: These results indicate that 3rd dose of COVID vaccine induces durable immunity in cancer patients and an additional dose can further stimulate immunity in a subset of patients with inadequate response.Funding: Leukemia lymphoma society, National Cancer Institute.Clinical trial identifier: NCT05016622.

Effects of Antibody Response after Booster Vaccination on SARS-CoV-2 Breakthrough Infections and Disease Outcomes in Advanced Cancer Patients: A Prospective Analysis of the Vax-on-Third Study

“…Since at that time 32% of the enrolled patients had already developed COVID-19 breakthrough infections, these pharmacological interventions cannot be considered applicable to the general study population. Evidence that additional booster doses may increase COVID-19 protection for cancer patients, even those who do not respond to the initial vaccine series, introduces potential confouders that we could not foresee at the beginning of this research [36].…”

Severe acute respiratory syndrome coronavirus 2 infection in patients with hematological malignancies in the Omicron era: Respiratory failure, need for mechanical ventilation and mortality in seronegative and seropositive patients

“…The fact that individuals with SARS‐CoV‐2 negative serology have worse outcomes than seropositive patients can be quite intuitive. In fact, SARS‐CoV‐2 serology can be considered an appropriate surrogate marker of patient immune response, being demonstrated that the higher the titer of the anti‐S antibody, the higher the likelihood of neutralization in neutralization assays [ 25 ].…”

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

“…Our study had a few limitations, the first being that we did not determine immunogenicity against different SARS-CoV-2 variants, particularly the Omicron variant, against which existing data show reduced vaccine efficacy [ 25 , 31 , 32 ]. The number of patients in each subcategory for analysis was lower in some therapies than others, limiting our ability to make conclusions for certain patient subsets.…”