Revaccination guide after established cell therapy for some, ‘evolving’ for others

Revaccination guide after established cell therapy for some, ‘evolving’ for others

07 November 2022

3 minutes of reading


Saullo JL, et al. The importance of revaccination after cell therapy. Presented at: NCCN Annual Meeting 2022: Hematologic Malignancies; October 14 and 15, 2022; New York.

Disclosures: Saullo does not report relevant financial disclosures.

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Guidelines on revaccination after cell therapy are clear for some patients but lack evidence-based consensus for others, according to an infectious disease expert who spoke at the 2022 NCCN Annual Meeting: Hematologic Malignancies.

“Cell therapy recipients are at high risk of infectious complications, including vaccine-preventable diseases,” jennifer l SaulloMD, Pharmacy, assistant professor of medicine in the division of infectious diseases at Duke University School of Medicine, told the audience. “Infection prevention measures, including vaccination, are critical to improving morbidity and mortality.”

Jennifer L Saullo

Revaccination of hematopoietic stem cell transplant(HSCT) is “essential” because immunity to vaccine-preventable diseases is “significantly decreased” after the procedure, according to Saullo.

Meanwhile, less is known about the immune system reaction after chimeric antigen receptor T-cell therapy. Revaccination recommendations are “evolving” for CAR-T recipients, with preliminary evidence suggesting variable decreased protection against certain vaccine-preventable diseases, Saullo said.

Professional societies and organizations, including the NCCN, provide recommendations on revaccination for vaccine-preventable diseases, COVID-19 and seasonal influenza, Saullo said, adding that clinicians should consider the following when contemplating revaccination after cell therapy:

  • What is the purpose of this vaccination?
  • When should this vaccine be given?
  • What vaccines are essential after cell therapy?

Saullo also emphasized that caregivers and close contacts of these patients should keep up their vaccinations to limit the risk of complications from infectious diseases.

Revaccination after HSCT

More data is available on revaccination among HSCT recipients, Saullo noted. However, a “complex interplay of humoral and cell-mediated deficiencies,” along with a litany of other factors, cause fluctuations in immune reconstitution that lead to declines in antibody titers for vaccine-preventable diseases, according to Saullo.

This, he added, requires multifaceted prophylactic interventions after HSCT, including antimicrobials, revaccination, and passive immunization.

“Basically, we’re recapitulating the ontogeny in these patients, treating them as if we were to restimulate a naive immune system and vaccinate them similar to what we would do with a newborn child,” he told the audience. “This has been identified … by the NIH as an area where there are a lot of gaps in terms of our knowledge.”

Saullo advised consulting relevant professional guidelines on revaccination timing, including those from the American Society for Blood and Marrow Transplantation/European Society for Blood and Marrow Transplantation. All recommend a time-based approach starting 3-6 months after the HSCT.

However, he questioned the wisdom of this approach “given all the factors that impact or delay T-cell recovery after [bone marrow transplant].”

Instead, Saullo advocated an immune recovery-based approach to revaccination after HSCT. Factors include time since transplant, type of vaccine used, and laboratory/physician criteria.

Core immunizations after the HSCT include steotococcus pneumonia; hepatitis A and B; herpes infection; and measles, mumps, and rubella (MMR).

Revaccination after CAR-T

Most of the emerging data on vaccination after CAR T-cell therapy relates to the use of CD19-targeted therapies to treat B-cell malignancies, such as B-cell acute lymphoblastic leukemia and diffuse lymphoma. large B cells, Saullo said.

“There are a multitude of infectious risks associated with CAR T-cell therapy, similar to what we have seen with hematopoietic stem cell transplantation,” he noted. “Many of these are related to specific patient or disease characteristics, but some are associated with CAR-T use itself.”

Although the CAR-T process depletes the body’s B cells, there is evidence that long-lived plasma cells that lack a CD19 receptor help the patient’s immune system maintain a long-term pathogen-specific immunoprotective memory after therapy with CAR T cells. Once that vaccine-preventable infectious disease is measles, for which there are limited preliminary data regarding stable levels of virus-specific immunoglobin G after CAR-T, Saullo said.

Few data exist on the effect of antigen-directed CAR-T on B-cell maturation, but the results of a small study suggested that recipients are more likely to have increased susceptibility to vaccine-preventable infectious diseases compared with those who do not. receiving CD19-targeted therapy. she added.

A schedule for revaccination of CAR-T recipients lacks consensus due to the limited data available, Saullo said.

“Bottom line: There are no strong recommendations,” he told the audience. “There are some recommendations based on expert opinion, and this is an area where we will continue to see management evolve. We may find that certain subsets may require a more robust post-CAR-T revaccination program.”

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