eLife (Mar 2023)

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

  • Astha Thakkar,
  • Kith Pradhan,
  • Benjamin Duva,
  • Juan Manuel Carreno,
  • Srabani Sahu,
  • Victor Thiruthuvanathan,
  • Sean Campbell,
  • Sonia Gallego,
  • Tushar D Bhagat,
  • Johanna Rivera,
  • Gaurav Choudhary,
  • Raul Olea,
  • Maite Sabalza,
  • Lauren C Shapiro,
  • Matthew Lee,
  • Ryann Quinn,
  • Ioannis Mantzaris,
  • Edward Chu,
  • Britta Will,
  • Liise-anne Pirofski,
  • Florian Krammer,
  • Amit Verma,
  • Balazs Halmos

DOI
https://doi.org/10.7554/eLife.83694
Journal volume & issue
Vol. 12

Abstract

Read online

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 two-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 third 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 fourth dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity, and neutralization activity, which were again assessed at baseline and 4 weeks. Results: We demonstrate that a third 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-SARS-CoV-2 (anti-S) antibody titers, T-cell activity, and neutralization activity against wild-type (WT) 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 third dose and were treated with a fourth 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 third 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 number: NCT05016622.

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