key: cord-0890559-4dfd79mk
authors: Dhakal, Binod; Abedin, Sameem; Fenske, Timothy; Chhabra, Saurabh; Ledeboer, Nathan; Hari, Parameswaran; Hamadani, Mehdi
title: Response to SARS-CoV-2 vaccinationin patients after hematopoietic cell transplantation and CAR T-cell therapy
date: 2021-08-04
journal: Blood
DOI: 10.1182/blood.2021012769
sha: 54ee6cd93c709d3e6a7148f3602c28bafee50793
doc_id: 890559
cord_uid: 4dfd79mk

nan

Coronavirus disease (COVID-19) caused by SARS-CoV-2 infection has affected tens of millions of people globally 1 Additionally, other vaccines using different platforms have shown efficacy ranging from 66% to 92% 3, 5 . Although vaccines are effective, the actual benefit to patients with hematological malignancies remain to be determined as several reports suggest inadequate immune response in these patients [6] [7] [8] [9] . Given the variable degree of immunosuppression associated with hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy, patients are often recommended to receive these vaccines approximately 6 months after the procedure, to hopefully allow for adequate immune recovery. However, data are lacking for immune response to SARS-CoV-2 vaccination in patients after HCT and CAR-T therapy.

Hence, we sought to assess the immune responses to COVID-19 vaccinations after received HCT and CAR-T therapy.

In the US, Pfizer, Moderna and Johnson and Johnson (J& J) vaccines have been approved by Food and Drug Administration (FDA) to be used in adults ≥18 years of age (≥12 years for Pfizer). Both Pfizer and Moderna are given 2 doses 3-4 weeks apart, while only one dose is given for J&J. We retrospectively assessed serological response following completed COVID-19 vaccination in patients after HCT and cellular therapy for hematological malignancies at our institution. Patients who were at least 2 weeks after vaccination scheme fully completed and had SARS-CoV-2 antibody checked were eligible. The blood samples were tested using enzyme immunoassay (EUROIMMUN) that tests for antibodies to the S1 domain of the SARS-CoV-2 spike protein 8, 10 . The sensitivity and specificity of the EUROIMMUN assay is 87.1% and 98.9% respectively for detection of the anti-spike humoral response to SARS-CoV-2 infection 10 .

This semiquantitative assay has consistently correlated with neutralizing immunity 10, 11 . Patient-, disease-and treatment characteristics were compared by vaccine response using t-test for continuous variable and chi-square test for the categorical variables. Statistical significance was determined at α<0.05, and all tests were two-sided. Data collection and analysis was approved Recent evidence points to inadequate immune response to COVID-19 vaccinations in patients with cancers including hematological malignancies 6, 9, 15, 16 and solid organ transplants 8, 17 . The seropositivity rates vary across these studies and this is attributed to different patient populations and variability in laboratory tests. It is important to note that CAR-T patients had low seroconversion rates in our study, but the small sample size precludes definite conclusions.

Whether this is due to underlying immune suppression, disease characteristic or preceding cytokine release syndrome needs to be evaluated.

Limitations of our study include lack of concurrent control group without HCT and CAR-T, lack of serial measurements after vaccination and assessment of humoral response only with no information on B cell numbers. 

BD collected data. BD and MH analyzed the data. BD wrote the first draft of manuscript, and all authors provided the critical input

Incyte Corporation; ADC Therapeutics; Cellerant Therapeutics

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