Predictors of impaired antibody response after <scp>SARS‐CoV</scp>‐2 <scp>mRNA</scp> vaccination in hematopoietic cell transplant recipients: A Japanese multicenter observational study

Mori, Yasuo; Uchida, Naoyuki; Harada, Taeko; Katayama, Yuta; Wake, Atsushi; Iwasaki, Hiromi; Eto, Tetsuya; Morishige, Satoshi; Fujisaki, Tomoaki; Ito, Yoshikiyo; Kamimura, Tomohiko; Takahashi, Tsutomu; Imamura, Yutaka; Tanimoto, Kazushi; Ishitsuka, Kenji; Sato, Junichi; Kawano, Noriaki; Tanimoto, Kazuki; Yoshimoto, Goichi; Choi, Ilseung; Hidaka, Tomonori; Ogawa, Ryo; Takamatsu, Yasushi; Miyamoto, Toshihiro; Akashi, Koichi; Nagafuji, Koji

doi:10.1002/ajh.26769

Cited by 12 publications

(7 citation statements)

References 44 publications

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“…The persistence of pre-cellular therapy SARS-CoV-2-specific humoral immunity was apparent based on the frequent presence of antibodies at the baseline time point in all cohorts, with generally higher antibody titers in patients tested earlier after cellular therapy. Notably, we did not observe associations with other clinical variables often considered in immunocompromised patients, such as the presence of GVHD, use of immunosuppressive therapies, or absolute lymphocyte counts (15)(16)(17)(18)(20)(21)(22)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 73%

“…Most studies focused on humoral immunity using binding antibody measurements, but evaluation of neutralizing antibodies and T cell responses provide additional data relevant to protection from severe infection (13,14). Studies in cellular therapy recipients have few participants vaccinated within the first 3-12 months, precluding conclusions about the optimal timing of vaccination after cellular therapy (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)

Hill,

Martens,

Young

et al. 2024

Preprint

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Background The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood. Objective To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy. Design Multicenter prospective observational study. Setting 34 centers in the United States. Participants 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022. Interventions SARS-CoV-2 vaccination as part of routine care. Measurements We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup. Results Anti-S IgG and neutralizing antibody responses increased with vaccination in HCT recipients irrespective of vaccine initiation timing but were unchanged in CAR-T cell therapy recipients initiating vaccines within 4 months. Anti-S IgG ≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell therapy recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy anti-S IgG levels. Limitations The majority of participants were adults and received mRNA vaccines. Conclusions These data support starting mRNA SARS-CoV-2 vaccination three to four months after allogeneic HCT, autologous HCT, and CAR-T cell therapy. Funding National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)

Hill,

Martens,

Young

et al. 2024

Preprint

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“…The antibody response in allo-HCT recipients is influenced by various factors, including the number of CD19+ cells, the timeframe following transplantation, complete remission status, the use of immunosuppressive drugs, and the levels of lymphocyte subpopulations [25]. Recent studies have demonstrated the safety and efficacy of the primary cycle of the mRNA-based SARS-CoV-2 vaccine BNT162b2 in allo-HCT recipients, with approximately 50-80% of subjects generating a protective immune response [7,[26][27][28][29]. However, limited data are available regarding neutralizing antibody levels in allo-HCT recipients following SARS-CoV-2 vaccination.…”

Section: Discussionmentioning

confidence: 99%

Spike-Specific Memory B Cell Response in Hematopoietic Cell Transplantation Recipients following Multiple mRNA-1273 Vaccinations: A Longitudinal Observational Study

Pettini,

Ciabattini,

Fiorino

et al. 2024

Vaccines

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Preventing SARS-CoV-2 infection is of utmost importance in allogeneic hematopoietic cell transplantation patients (allo-HCT), given their heightened susceptibility to adverse outcomes associated with SARS-CoV-2 infection. However, limited data are available regarding the immune response to COVID-19 vaccines in these subjects, particularly concerning the generation and persistence of spike-specific memory response. Here, we analyzed the spike-specific memory B cells in a cohort of allo-HCT recipients vaccinated with multiple doses of the mRNA-1273 vaccine and monitored the spike-specific antibody response from baseline up to one month after the fourth dose. After the primary vaccine series, the frequency of spike-specific B cells, detected within the pool of Ig-switched CD19+ cells, significantly increased. The booster dose further induced a significant expansion, reaching up to 0.28% of spike-specific B cells. The kinetics of this expansion were slower in the allo-HCT recipients compared to healthy controls. Spike-specific IgG and ACE2/RBD binding inhibition activity were observed in 80% of the allo-HCT recipients after the first two doses, with a significant increase after the third and fourth booster doses, including in the subjects who did not respond to the primary vaccine series. Additionally, 87% of the allo-HCT recipients exhibited positive cross-inhibition activity against the BA.1 variant. Our findings provide evidence that allo-HCT recipients need repeated doses of the mRNA-1273 vaccine to induceSARS-CoV-2 specific immune response similar to that observed in healthy individuals. This is particularly crucial for vulnerable individuals who may exhibit a limited response to the primary series of SARS-CoV-2 vaccination.

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“…After applying the eligibility criteria, 102 studies remained, forming the evidentiary basis for the guideline recommendations: 24 systematic reviews, 11, 14 RCTs, 6,[44][45][46][47][48][49][50][51][52][53][54][55][56] and 64 nonrandomized studies. [85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120] The ...…”

Section: Characteristics Of Studies Identified In the Literature Searchmentioning

confidence: 99%

Vaccination of Adults With Cancer: ASCO Guideline

Kamboj,

Bohlke,

Baptiste

et al. 2024

JCO

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ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more. PURPOSE To guide the vaccination of adults with solid tumors or hematologic malignancies. METHODS A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and nonrandomized studies on the efficacy and safety of vaccines used by adults with cancer or their household contacts. This review builds on a 2013 guideline by the Infectious Disease Society of America. PubMed and the Cochrane Library were searched from January 1, 2013, to February 16, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS A total of 102 publications were included in the systematic review: 24 systematic reviews, 14 RCTs, and 64 nonrandomized studies. The largest body of evidence addressed COVID-19 vaccines. RECOMMENDATIONS The goal of vaccination is to limit the severity of infection and prevent infection where feasible. Optimizing vaccination status should be considered a key element in the care of patients with cancer. This approach includes the documentation of vaccination status at the time of the first patient visit; timely provision of recommended vaccines; and appropriate revaccination after hematopoietic stem-cell transplantation, chimeric antigen receptor T-cell therapy, or B-cell–depleting therapy. Active interaction and coordination among healthcare providers, including primary care practitioners, pharmacists, and nursing team members, are needed. Vaccination of household contacts will enhance protection for patients with cancer. Some vaccination and revaccination plans for patients with cancer may be affected by the underlying immune status and the anticancer therapy received. As a result, vaccine strategies may differ from the vaccine recommendations for the general healthy adult population vaccine. Additional information is available at www.asco.org/supportive-care-guidelines .

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Predictors of impaired antibody response after SARS‐CoV‐2 mRNA vaccination in hematopoietic cell transplant recipients: A Japanese multicenter observational study

Cited by 12 publications

References 44 publications

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)

Spike-Specific Memory B Cell Response in Hematopoietic Cell Transplantation Recipients following Multiple mRNA-1273 Vaccinations: A Longitudinal Observational Study

Vaccination of Adults With Cancer: ASCO Guideline

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