Immune Responses to SARS-CoV-2 Vaccination in Young Patients with Anti-CD19 Chimeric Antigen Receptor T Cell-Induced B Cell Aplasia

Jarisch, Andrea; Wiercinska, Eliza; Huenecke, Sabine; Bremm, Melanie; Cappel, Claudia; Hauler, Julian; Rettinger, Eva; Soerensen, Jan; Hellstern, Helen; Klusmann, Jan‐Henning; Ciesek, Sandra; Bönig, Halvard; Bader, Peter

doi:10.1016/j.jtct.2022.04.017

Cited by 14 publications

(7 citation statements)

References 24 publications

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“…Multivariate analysis also suggested an association between the anti-S titers of 0.8 U/ml and CD19. This has also been shown in studies where CD19 is associated with antibody acquisition at the time of COVID-19 vaccination in CAR-T therapy, in which the actual amount of CD19 is extremely reduced (16,17). The importance of CD19 in COVID-19 vaccination is demonstrated in the present study.…”

Section: Discussionsupporting

confidence: 86%

COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma

Tsutsumi,

Ito,

Horikita

et al. 2023

Mol Clin Oncol

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Most hematologic diseases are immunosuppressed, either by the disease itself or by treatment. As such, the implementation of vaccination is largely at the discretion of the attending physician. In this context, an objective measure is needed, therefore the index of vaccination against coronavirus disease 2019 (COVID-19) in B-cell lymphomas treated with antibody therapy against CD20 (including after the completion of therapy) was examined. A total of 40 patients with B-cell lymphoma during or after antibody therapy against CD20 were vaccinated twice with the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer, Inc. and BioNTech SE.) at 3-week intervals and then again six months later with the same vaccine or mRNA-1273 (Moderna, Inc.). Antibody testing was conducted ~1 month after the third vaccination. Analysis was performed using the antibody titers to the anti-spike immunoglobulin assay, with a titer of 0.8 U/ml or higher (considered positive) and a titer of 264 U/ml or higher (considered the value at which the efficacy of the vaccine can be fully expected). Significant factors of antibody acquisition were identified when i) antibody titers were 0.8 U/ml or higher (CD4 ≥400/µl), ii) no anti-CD20 antibody maintenance therapy was undertaken (CD19 ≥100/µl), iii) patients were not on treatment (CD4 ≥400/µl), or 4) at least six months had passed since treatment ended (CD19 ≥100/µl). When antibody titers were 264 U/ml or higher, the treatment method, the stage of the primary disease and other factors related to the condition treatment method of the patient were relevant. When these were analyzed by multivariate analysis, the significant factor when antibody titers were set to 0.8 U/ml was CD19 ≥100/µl. In contrast, when setting them to 264 U/ml or higher, CD4 ≥400/µl was not significant, but there was a tendency for it to be related. The findings of the present study on vaccine-induced antibody acquisition in patients with B-cell lymphoma indicated that it is desirable to have a CD19 titer of at least 100/µl and a CD4 titer of at least 400/µl (both conditions should be met), and that no maintenance therapy with anti-CD20 antibody should be administered for at least six months after the last treatment or completion of the treatment. Interestingly, when the criteria for antibody titers were compared between 0.8 U/ml, where antibody titer is detected, and 264 U/ml, where vaccine efficacy is expected, several key factors were different. It is possible that these key factors may change depending on the antibody titer used as a criterion.

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Section: Discussionsupporting

confidence: 86%

COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma

Tsutsumi,

Ito,

Horikita

et al. 2023

Mol Clin Oncol

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“…Contrarily to the general (healthy) population, cellular responses to SARS-CoV-2 have been found to be reduced in vulnerable populations, such as patients with primary immunodeficiencies or those secondarily immunocompromised ( 8 – 25 ), including those with autoimmune diseases ( 9 , 26 – 32 ). Most immunosuppressive agents, including glucocorticoids, mycophenolate, methotrexate, tumor necrosis factor (TNF) inhibitors, tocilizumab, abatacept, and rituximab have been associated with poor humoral responses in patients with autoimmune diseases after SARS-CoV-2 vaccination ( 26 – 28 , 32 ), and the highest risk has been identified with the use of rituximab ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, a proportion of patients with immune-debilitating diseases have been described to lack complete humoral and/or cellular responses to SARS-CoV-2 vaccination, mainly to messenger RNA (mRNA) vaccines. These conditions include primary immunodeficiencies ( 8 – 10 ), neoplastic diseases ( 9 , 11 – 13 ), HIV infection and low CD4 lymphocyte counts ( 14 ), and liver cirrhosis ( 15 ), as well as patients on hemodialysis ( 16 , 17 ), recipients of solid organ transplants ( 9 , 16 , 18 – 20 ), stem cell transplantation ( 21 – 24 ), or CAR T-cell therapy ( 22 , 24 , 25 ), and patients with autoimmune diseases, such as rheumatoid arthritis (RA), spondyloarthropathies, systemic lupus erythematosus (SLE), mixed connective tissue disease, multiple sclerosis, autoimmune hepatitis, and different types of vasculitis, which are in turn treated with a wide variety of immunosuppressive agents ( 9 , 26 – 32 ).…”

Section: Introductionmentioning

confidence: 99%

Cellular and humoral responses after second and third SARS-CoV-2 vaccinations in patients with autoimmune diseases treated with rituximab: specific T cell immunity remains longer and plays a protective role against SARS-CoV-2 reinfections

et al. 2023

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BackgroundHumoral and cellular immune responses are known to be crucial for patients to recover from COVID-19 and to protect them against SARS-CoV-2 reinfection once infected or vaccinated.ObjectivesThis study aimed to investigate humoral and T cell responses to SARS-CoV-2 vaccination in patients with autoimmune diseases after the second and third vaccine doses while on rituximab and their potential protective role against reinfection.MethodsTen COVID-19-naïve patients were included. Three time points were used for monitoring cellular and humoral responses: pre-vaccine to exclude virus exposure (time point 1) and post-second and post-third vaccine (time points 2 and 3). Specific IgG antibodies were monitored by Luminex and T cells against SARS-CoV-2 spike-protein by ELISpot and CoVITEST. All episodes of symptomatic COVID-19 were recorded.ResultsNine patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and one with an undifferentiated autoimmune disease were included. Nine patients received mRNA vaccines. The last rituximab infusion was administered for a mean (SD) of 15 (10) weeks before the first vaccine and six patients were CD19-B cell-depleted. After a mean (SD) of 19 (10) and 16 (2) days from the second and third vaccine dose, IgG anti-SARS-CoV-2 antibodies were detected in six (60%) and eight (80%) patients, respectively. All patients developed specific T cell responses by ELISpot and CoVITEST in time points 2 and 3. Previous B cell depletion correlated with anti-SARS-CoV-2 IgG levels. Nine (90%) patients developed mild COVID-19 after a median of 7 months of the third dose.ConclusionRituximab in patients with autoimmune diseases reduces humoral responses but does not avoid the development of T cell responses to SARS-CoV-2 vaccination, which remain present after a booster dose. A steady cellular immunity appears to be protective against subsequent reinfections.

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“…However, in another study, Tamari et al reported that 77% of patients achieved positive neutralization activity 3 months after COVID-19 vaccination [109]. Jarisch et al also demonstrated a robust T cell response, especially in CD4 lymphocyte subset, in eight lymphoma patients who received CD19 CAR T-cells [110]. Moreover, Parvathaneni et al showed that despite lower humoral response to SAR-CoV2 vaccines, spikespecific T-cell response to mRNA-based vaccines (BNT162b2 and mRNA-1273) in 12 patients treated with CD19 CAR T-cells was comparable to healthy control [111].…”

Section: Killed/inactivatedmentioning

confidence: 99%

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Wudhikarn

Perales

2022

Bone Marrow Transplant

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CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.

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Immune Responses to SARS-CoV-2 Vaccination in Young Patients with Anti-CD19 Chimeric Antigen Receptor T Cell-Induced B Cell Aplasia

Cited by 14 publications

References 24 publications

COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma

COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma

Cellular and humoral responses after second and third SARS-CoV-2 vaccinations in patients with autoimmune diseases treated with rituximab: specific T cell immunity remains longer and plays a protective role against SARS-CoV-2 reinfections

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

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