What Is the Optimal Timing of COVID-19 Vaccination Following Cellular Therapy?

Humoral and cellular responses following COVID-19 mRNA vaccination were found to be similar between patients who received the vaccine fewer than 4 months vs 4 to 12 months after cellular therapy, according to study results published in Clinical Infectious Diseases.

Researchers conducted a multicenter prospective, observational study between April 2021 and June 2022 at 30 cancer centers in the United States to evaluate whether immunogenicity following SARS-CoV-2 vaccination differs if initiated fewer than 4 months vs 4 to 12 months after cellular therapy. Patients who had undergone allogeneic or autologous hematopoietic cell transplantation (HCT), or chimeric antigen receptor T-cell (CAR-T) therapy, and planned to receive a first post-cellular therapy SARS-COV-2 vaccine within 12 months of therapy were eligible for study enrollment. Blood samples were obtained prior to and after vaccination at up to 5 points in time and tested for SARS-CoV-2 anti-spike immunoglobulin (Ig) G, neutralizing antibodies (nAbs) for certain SARS-CoV-2 variants, and SARS-CoV-2-specific T-cell receptors. The primary study objective was to compare immunogenicity between patients grouped by timing of COVID-19 vaccination after receipt of cellular therapy (<4 vs 4-12 months). The researchers used adjusted logistic and linear regression models to assess the effect of vaccination timing and cellular therapy type on anti-SARS-CoV-2 spike IgG and T-cell responses.  

A total of 466 patients (aged 60-69 years at cellular therapy, 32%; men, 54%; White, 76%) were included in the study, of whom 231 were allogeneic HCT recipients, 170 were autologous HCT recipients, and 65 had undergone CAR-T therapy. Overall, 231 and 235 patients were vaccinated fewer than 4 months and between 4 and 12 months after cellular therapy, respectively.

Irrespective of vaccine initiation timing, nAb responses increased with subsequent vaccination among HCT recipients. However, nAb responses were unchanged among CAR-T therapy recipients who were vaccinated within the 4 months following cellular therapy.

The percentage of autologous and allogeneic HCT recipients with positive antibody responses increased with vaccination and was similar at the end-of-study timepoint, irrespective of vaccination timing. In contrast, the percentage of patients on CAR-T therapy with positive antibody responses declined with vaccination. By the last timepoint, the SARS-CoV-2 anti-spike IgG threshold of 2500 U/mL was reached in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T therapy recipients, respectively.

Among all cohorts, SARS-CoV-2-specific T-cell responses increased with vaccination and were similar by vaccine initiation timing. Positive T-cell responses were achieved in 55%, 81%, and 61% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively.

In the multivariable analysis, prior COVID-19 infection and vaccination as well as absolute CD19⁺ B-cell count at baseline were identified as significant predictors of increased of SARS-CoV-2 anti-spike IgG values. Prior COVID-19 infection and vaccination also were significantly associated with increased SARS-CoV-2-specific T-cell responses. Overall, humoral and cellular responses did not significantly differ on the basis of vaccination timing after cellular therapy.

The researchers noted that vaccine-related adverse events of grade 3 severity and higher were uncommon. Moreover, there were no vaccine-related recurrent immune-associated toxicities observed among patients in the CAR-T therapy group.

Limitations of this study include the observational design, potential residual confounding, and insufficient power for comparisons in the CAR-T therapy group.

“[T]hese data support ensuring appropriate vaccination of patients prior to receiving cellular therapy in addition to starting mRNA SARS-CoV-2 vaccination within three to four months after allogeneic HCT, autologous HCT, or CAR-T cell therapy,” the researchers concluded.

Disclosure: This research was supported by Novartis, Adaptive Biotechnologies, and LabCorp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Infectious Disease Advisor