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638 Cellular Immune Responses to BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia

Program: Oral and Poster Abstracts
Type: Oral
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological II
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, Biological, CLL, Clinically Relevant, Immunodeficiency, Diseases, Immune Disorders, SARS-CoV-2/COVID-19, Infectious Diseases, Therapies, Lymphoid Malignancies, Vaccines
Monday, December 13, 2021: 10:45 AM

Gilad Itchaki, MD1,2*, Lior Rokach, PhD3*, Ohad Benjamini, MD4,5*, Osnat Bairey, MD6,7*, Adi Sabag8*, Helly Vernitsky9*, Hila Cohen10*, Shahar Rotem10*, Uri Elia10*, Pia Raanani, MD11,12, Erez Bar-Haim, PhD10* and Tamar Tadmor, MD8,13*

1Hematology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel
2Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv, Israel
3Ben-Gurion University of the Negev, Beer-Sheva, ISR
4Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel
5Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
6Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;, Tel Aviv, Israel
7Davidoff Cancer Center, Rabin Medical Center Beilinson Hospital,, Rabin Medical Center Beilinson Campus, Petah Tikva, Israel
8Hematology Unit, Bnai Zion Medical Center, Haifa, Israel
9Sheba Medical Center, Tel Hashomer, ISR
10Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
11Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah –Tikva, Israel
12Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
13The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

Background: Patients with chronic lymphocytic leukemia (CLL) are known to have a suboptimal immune response of both humoral and cellular arms. Recently, a BNT162b2 mRNA COVID-19 vaccine was introduced with a high efficacy of 95% in immunocompetent individuals. Approximately half of the patients with CLL fail to mount a humoral response to the vaccine, as detected by anti-spike antibodies. Currently, there is no data available regarding T-cell immune responses following the vaccine of these patients.

Aim of the study: To investigate T-cell response determined by interferon gamma (IFNγ) secretion in patients with CLL following BNT162b mRNA Covid-19 vaccine, in comparison with serologic response.

Methods: CLL patients from 3 medical centers in Israel were included in the study. All patients received two 30-μg doses of BNT162b2 vaccine (Pfizer), administered intramuscularly 3 weeks apart. For evaluation of SARS-CoV-2 Spike-specific T-cell responses, blood samples were stimulated ex-vivo with Spike protein and secreted IFNγ was quantified (ELISA DuoSet, R&D Systems, Minneapolis, Minnesota, USA). T-cell immune response was considered to be positive for values above 25 pg/ml of Spike-specific response. T-cell subpopulations were characterized by flow cytometry (CD3, CD4, CD8). Anti-spike antibody tests were performed using the Architect AdviseDx SARS-CoV-2 IgG II (Abbot, Lake Forest, Illinois, USA). Statistical analysis was performed using Mann–Whitney test for continuous variables while the Wald Chi-square test was used for comparing categorical variables.

Results: 83 patients with CLL were tested for T-cell response. Blood samples were collected after a median time of 139 days post administration of the second dose of vaccine (IQ range 134-152). Out of 83 patients, 68 were eligible for the analysis (with positive internal control). Median age of the cohort was 68 years (56-72); and 44 (65%) were males. 19 (28%) patients were treatment-naïve, most of whom were Binet stage A or B. 31 (46%) patients were on therapy: 17 with a BTK-inhibitor, and 13 with a venetoclax-based regimen. 29 (42%) patients were previously treated with anti-CD20, 13 of whom in the 12 months period prior to vaccination.

T cell immune response to the vaccine was evident in 22 (32%) patients. CIRS Score>6 and specifically hypertension were statistically significantly associated with a lower T-cell response (univariate analysis, p-value<0.05). Variables that were associated with the development of T-cell response were presence of del(13q), IgM ≥ 40 mg/dL, and IgA ≥ 80 mg/dL (p-value 0.05-0.1). There was no significant difference with regards to age, gender, other CLL-specific prognostic markers, treatment, and T-cell subpopulation distribution according to flow cytometry (Table 1).

The presence of T-cell response highly correlated with both the detection of anti-spike IgG antibodies following the second dose (p=0.0239) and at the time of T-cell testing (n=66, p=0.048, Table 2). While 50% of patients who tested positive for anti-spike IgG antibodies also developed positive T-cell response, only 17% of patients who did not develop T-cell response, tested positive for anti-spike antibodies. Importantly, 24% of the patients who tested negative for anti-spike IgG antibodies, developed positive T cell response. Moreover, the level of the T-cell response (log transformed) correlated linearly with (log transformed) anti-spike IgG titer (adjusted r=0.26 and p =0.026 according to Pearson correlation, Figure 1).

Conclusion: We show that cellular immune response to the BNT162b2 mRNA COVID-19 vaccine, is blunted in most CLL patients and that there is a correlation between T-cell response and serologic response to the vaccine. These results need to be validated in a larger cohort.

Disclosures: Itchaki: AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Benjamini: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tadmor: AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding.

*signifies non-member of ASH