SARS-CoV-2 vaccination in the first year after allogeneic hematopoietic cell transplant: a prospective, multicentre, observational study

Hill, Joshua A.; Märtens, Michael; Young, Jo Anne H.; Bhavsar, Kavita V.; Kou, Jianqun; Chen, Min; Lee, Lik Wee; Baluch, Aliyah; Dhodapkar, Madhav V.; Nakamura, Ryotaro; Peyton, Kristin; Shahid, Zainab; Armistead, Paul M.; Westervelt, Peter; McCarty, John M.; McGuirk, Joseph P.; Hamadani, Mehdi; DeWolf, Susan; Hosszu, Kinga; Sharon, Elad; Spahn, Ashley; Toor, Amir A.; Waldvogel, Stephanie; Greenberger, Lee M.; Auletta, Jeffery J.; Horowitz, Mary M.; Riches, Marcie L.; Perales, Miguel-Ángel

doi:10.1016/j.eclinm.2023.101983

Cited by 18 publications

(17 citation statements)

References 40 publications

(56 reference statements)

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“…52,57 The efficacy of these vaccines decreased after the emergence of Omicron variants. 58,59 Of note, pivotal phase three trials of these vaccines excluded immunocompromised patients 54 or included only a handful of cancer patients. 52,55 There is robust evidence that antibody responses to COVID-19 vaccines are blunted in HCT and CAR-T-cell therapy.…”

Section: Vaccination Strategies and Recommendationsmentioning

confidence: 99%

“…However, after two doses of the vaccine an antibody response (anti-spike IgG) is present in 69%-89% of allogeneic HCT 66,68,69,[73][74][75][76][77] and 60%-87% of autologous HCT recipients. 66,76 A third dose improves waning (or absent) antispike antibody responses 59,73,[78][79][80][81][82] and neutralizing antibodies, 59,83 but humoral responses remain low even after a third dose. 59,73,[78][79][80][81][82] Data on neutralizing antibodies and T-cell responses, which are better surrogates for protection from severe COVID-19, are scarce.…”

Section: Vaccine Immunogenicity After Hctmentioning

confidence: 99%

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COVID‐19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)‐T‐cell therapy

Kampouri,

Hill,

Dioverti

2023

Transplant Infectious Dis

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More than 3 years have passed since Coronavirus disease 2019 (COVID‐19) was declared a global pandemic, yet COVID‐19 still severely impacts immunocompromised individuals including those treated with hematopoietic cell transplantation (HCT) and chimeric antigen receptor‐T‐cell therapies who remain at high risk for severe COVID‐19 and mortality. Despite vaccination efforts, these patients have inadequate responses due to immunosuppression, which underscores the need for additional preventive approaches. The optimal timing, schedule of vaccination, and immunological correlates for protective immunity remain unknown. Antiviral therapies used early during disease can reduce mortality and severity due to COVID‐19. The combination or sequential use of antivirals could be beneficial to control replication and prevent the development of treatment‐related mutations in protracted COVID‐19. Despite conflicting data, COVID‐19 convalescent plasma remains an option in immunocompromised patients with mild‐to‐moderate disease to prevent progression. Protracted COVID‐19 has been increasingly recognized among these patients and has been implicated in intra‐host emergence of SARS‐CoV‐2 variants. Finally, novel SARS‐CoV2‐specific T‐cells and natural killer cell‐boosting (or ‐containing) products may be active against multiple variants and are promising therapies in immunocompromised patients.

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Section: Vaccination Strategies and Recommendationsmentioning

confidence: 99%

Section: Vaccine Immunogenicity After Hctmentioning

confidence: 99%

COVID‐19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)‐T‐cell therapy

Kampouri,

Hill,

Dioverti

2023

Transplant Infectious Dis

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“…During the first year after CAR-T cell therapy, only nearly 40–60% of patients achieve a protective response with vaccinations, including highly immunogenic vaccines such as SARS-CoV-2 [31–33,34 ▪▪ ]. In addition to the poor initial “take,” rapidly waning titers have been observed to vaccines that typically lead to a durable response, such as the MMR vaccine, in hematopoietic cell transplant recipients [35].…”

Section: Trials In Immunocompromised Populations: Car-t Cell Recipientsmentioning

confidence: 99%

Targeting enhanced neutralizing antibody responses via increased germinal center activity: early-phase vaccine trials with novel clinical designs

Hahn,

Hill,

Kublin

2023

Current Opinion in HIV and AIDS

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Purpose of review Recent advances in the understanding of the difficult immunologic requirements for the induction of broadly neutralizing antibodies for HIV have spurred interest in optimizing vaccine approaches intended to stimulate a robust germinal center reaction. In preclinical models, techniques to optimize the germinal center response have included alterations in the timing, dose, and delivery method of immunogens and have resulted in substantially enhanced germinal center responses in lymph nodes and neutralizing antibodies in serum. One of the most promising approaches involves splitting the initial dose of vaccine into a series of gradual escalating doses administration (“fractional escalating doses”). In principle, these techniques may have broad implications for vaccines targeting a robust antibody response. Recent findings We review the upcoming vaccine trials that will test these concepts in clinical practice. The trials include both HIV and non-HIV immunogens, and will involve testing these concepts in both healthy adults and immunocompromised persons. Summary There are multiple trials that will test whether techniques to alter vaccine delivery such as fractional escalating doses enhances immunologic outcomes.

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“…75,79 Immunogenicity analysis (humoral and cell-mediated immunity) from a recent observational cohort study of allogeneic HCT recipients supports the commencement of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revaccination at 3 months post-transplantation, immune responses were not influenced by concurrent GvHD or immunosuppressive regimen. 85 The third dose should be given at least 28 days after the second dose.…”

Section: Covid-19 Vaccinesmentioning

confidence: 99%

Vaccine schedule recommendations and updates for patients with hematologic malignancy post‐hematopoietic cell transplant or CAR T‐cell therapy

Reynolds,

Hall,

Teh

2023

Transplant Infectious Dis

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Revaccination after receipt of a hematopoietic cell transplant (HCT) or cellular therapies is a pillar of patient supportive care, with the potential to reduce morbidity and mortality linked to vaccine‐preventable infections. This review synthesizes national, international, and expert consensus vaccination schedules post‐HCT and presents evidence regarding the efficacy of newer vaccine formulations for pneumococcus, recombinant zoster vaccine, and coronavirus disease 2019 in patients with hematological malignancy. Revaccination post‐cellular therapies are less well defined. This review highlights important considerations around poor vaccine response, seroprevalence preservation after cellular therapies, and the optimal timing of revaccination. Future research should assess the immunogenicity and real‐world effectiveness of new vaccine formulations and/or vaccine schedules in patients post‐HCT and cellular therapy, including analysis of vaccine response that relates to the target of cellular therapies.

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SARS-CoV-2 vaccination in the first year after allogeneic hematopoietic cell transplant: a prospective, multicentre, observational study

Cited by 18 publications

References 40 publications

COVID‐19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)‐T‐cell therapy

COVID‐19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)‐T‐cell therapy

Targeting enhanced neutralizing antibody responses via increased germinal center activity: early-phase vaccine trials with novel clinical designs

Vaccine schedule recommendations and updates for patients with hematologic malignancy post‐hematopoietic cell transplant or CAR T‐cell therapy

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