Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies

Greenberger, Lee M.; Saltzman, Larry A.; Senefeld, Jonathon W.; Johnson, Patrick W.; DeGennaro, Louis J.; Nichols, Gwen

doi:10.1016/j.ccell.2021.07.012

Cited by 239 publications

(341 citation statements)

References 9 publications

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“…Compared with other studies, we report a higher rate of seroconversion in patients on active BTKi monotherapy. 4 , 5 Here, we found that 66.7% (4/6) of CLL patients and 50% (2/4) of other NHL patients did develop high‐titer IgG antibodies after mRNA vaccination. In a study by Herishanu et al 4 only 16% (8/50) of CLL patients treated with a BTKi responded to vaccination with BNT162b2.…”

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confidence: 57%

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Serologic response to mRNA COVID‐19 vaccination in lymphoma patients

et al. 2021

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confidence: 57%

“…With regard to anti‐CD20 mAbs, our results are consistent with a growing number of reports that patients on active, or with recent anti‐CD20 mAb treatment do not respond to vaccination. 4 , 5 , 6…”

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confidence: 99%

Serologic response to mRNA COVID‐19 vaccination in lymphoma patients

et al. 2021

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“…In the largest study examining patients with HM to date, including 1455 patients, seroprotective antibodies were analyzed 14 days after the second dose of mRNA vaccine. The study showed superior immune responses to both mRNA vaccines in patients with leukemia, MM, and Hodgkin's lymphoma compared to those with B-cell NHL subtypes 126 . These suboptimal response rates to mRNA-based vaccines in patients with HM are in congruence with those demonstrated previously with other non-live vaccines against a variety of illnesses 127 , 128 , 129 .…”

Section: Current State Of Sars-cov-2 Vaccine Responses In Patients With Hematologic Malignanciesmentioning

confidence: 85%

“…Interestingly, the one CD19+CAR-T patient who responded positively had relapsed CLL immediately prior to the mRNA vaccination. Also, the one BCMA+CAR-T patient who responded negatively, had his immunity analyzed 14 days after the second mRNA vaccine dose, likely due to insufficient time to generate an antibody response 126 . Considering that B-cell aplasia is a clinical surrogate marker of CAR-T persistence, the robust antibody response in patients with MM may forecast a lack of durability of BCMA+CAR-T. Longitudinal data, both related to CAR-T efficacy as well as vaccine responses in CAR-T recipients, will be awaited.…”

Section: Data On Vaccine Response In Car-t Recipients and Additional Immune Considerationsmentioning

confidence: 99%

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

Meir

Abid

2021

Transplantation and Cellular Therapy

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Chimeric antigen receptor T-cell (CAR-T) therapy has shown unprecedented response rates in patients with relapsed/refractory (R/R) hematological malignancies. While CAR-T therapy renders hope to heavily pre-treated patients, the rapid commercialization and cumulative immunosuppression predispose patients to infections for a prolonged period. CAR-T poses distinctive short- and long-term toxicities and infection risks among patients who receive CAR-T after multiple prior treatments, often including hematopoietic cell transplantation. The acute toxicities include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. The long-term B-cell depletion, hypogammaglobulinemia, and cytopenia further predispose patients to severe infections and abrogate the remission success achieved by the living drug. These on-target-off-tumor toxicities deplete B-cells across the entire lineage and further diminish immune responses to vaccines. Early observational data suggest that patients with hematologic malignancies may not mount an adequate humoral and cellular response to SARS-CoV-2 vaccines. In this review, we summarize the immune comprising factors indigenous to CAR-T recipients. We discuss the immunogenic potential of different SARS-CoV-2 vaccines based on the differences in the manufacturing platforms among CAR-T recipients. Given the lack of data related to the safety and efficacy of SARS-CoV-2 vaccines in this distinctively immunosuppressed cohort, we summarize the infection risks associated with FDA-approved CAR-T constructs and the potential determinants of vaccine responses. The review further highlights the potential need for booster vaccine dosing and the promise for heterologous prime-boosting in CAR-T recipients.

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“…Even BTK-inhibitors were associated with impaired response to COVID-19 vaccination in CLL [ 219 ]. A study of 1445 patients with hematologic malignancies immunized with either the Moderna (mRNA-1273) or Pfizer (BNT162b2) vaccine included 650 patients with CLL and 7 with HCL [ 220 ]. All 7 HCL patients achieved positive levels of antibodies, compared with only 64.2% of the patients with CLL.…”

Section: Treating Hcl In the Era Of Covid-19mentioning

confidence: 99%

Diagnosis and treatment of hairy cell leukemia as the COVID-19 pandemic continues

Kreitman

Arons

2022

Blood Reviews

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Hairy cell leukemia (HCL) is an indolent B-cell malignancy, usually driven by the BRAF V600E mutation. For 30 years, untreated and relapsed HCL was successfully treated with purine analogs, but minimal residual disease (MRD) remained in most patients, eventually causing relapse. Repeated purine analogs achieve decreasing efficacy and increasing toxicity, particularly to normal T-cells. MRD-free complete remissions (CRs) are more common using rituximab with purine analogs in both 1 st -line and relapsed settings. BRAF inhibitors and Ibrutinib can achieve remission, but due to persistence of MRD, must be used chronically to prevent relapse. BRAF inhibition combined with Rituximab can achieve high MRD-free CR rates. Anti-CD22 recombinant immunotoxin moxetumomab pasudotox is FDA-approved in the relapsed setting and is unique in achieving high MRD-free CR rates as a single-agent. Avoiding chemotherapy and rituximab may be important in ensuring both recovery from COVID-19 and successful COVID-19 vaccination, an area of continued investigation.

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Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies

Cited by 239 publications

References 9 publications

Serologic response to mRNA COVID‐19 vaccination in lymphoma patients

Serologic response to mRNA COVID‐19 vaccination in lymphoma patients

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

Diagnosis and treatment of hairy cell leukemia as the COVID-19 pandemic continues

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