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254 Antibody Response after One and/or Two Doses of BNT162b2 Anti- Sars-Cov-2 mRNA Vaccine in Patients Treated By CAR T-Cells Therapy

Program: Oral and Poster Abstracts
Type: Oral
Session: 704. Cellular Immunotherapies: Cellular Therapies-Immune Interactions, Lineage Switching and CNS targets
Hematology Disease Topics & Pathways:
Biological, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinically Relevant, Therapies, Vaccines
Saturday, December 11, 2021: 2:15 PM

Thomas Gastinne, MD1*, Amandine Le Bourgeois, MD2*, Marianne Coste-Burel, MD, PhD3*, Thierry Guillaume, MD, PhD4*, Pierre Peterlin5*, Alice Garnier, MD2*, Berthe-Marie Imbert6*, Thomas Drumel, PharmD3*, Béatrice Mahé, MD7*, Viviane Dubruille, MD2*, Nicolas Blin, MD2*, Anne Lok, MD2*, Cyrille Touzeau, MD, PhD8*, Benoit Tessoulin, MD, PhD9*, Maxime Jullien, MD2*, Sophie Vantyghem, MD2*, Marie C Bene, PharmSci, PhD10*, Philippe Moreau, MD, PhD11*, Steven Le Gouill12 and Patrice Chevallier, MD13

1Clinical Hematology, University Hospital of Nantes,, Nantes Cedex 1, France
2Clinical Hematology, Nantes University Hospital, Nantes, France
3Virology, Nantes University Hospital, Nantes, France
4CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France
5Clinical Hematology, HOPITAL HOTEL DIEU ET HME, NANTES CEDEX 1, France
6Virology, Nantes University Hospital, NANTES, France
7Centre Hospitalier Universitaire de Nantes, Nantes, France
8Hématologie, CHU de Nantes, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Nantes, France
9Université de Nantes, CNRS, INSERM, CRCINA, Nantes, France, Nantes, France
10Nantes University Hospital, Hematology Biology, Nantes, France
11Université de Nantes, INSERM UMR 892, CNRS UMR 6299, Nantes, France
12Service d’hématologie clinique du CHU de Nantes, INSERM CRCINA Nantes-Angers, NeXT Université de Nantes, Nantes, France
13D'Hematologie, Nantes University Hospital, Nantes, France

Introduction: Data regarding the efficacy of anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) messenger RNA vaccines in immunocompromised hosts are scarce and no data yet appear to be available for patients with hematological malignancies who also received chimeric antigen receptor-T (CAR-T) cells therapy.

Methods: The efficacy and safety of one and/or two injections of the BNT162b2 (Pfizer-BioNTech) vaccine was evaluated retrospectively in 23 CAR-T recipients in our Hematology Department, compared to a cohort of 25 healthy caregivers, vaccinated concomitantly between January 28 and May 31, 2021. None of these individuals had a previous clinical history of COVID-19.

Results: Overall, the patients (14 males and 9 females) had a median age of 62 years old (range: 21-79) and had received CAR-T for high-grade lymphoma (n= 20) or acute lymphoblastic leukemia (n= 3). Eight and 3 had been respectively previously autografted or allografted and two were allografted after CAR-T. All patients were pretreated for lymphodepletion by fludarabine + cyclophosphamide before CAR-T infusion. The CAR-T provided were axicabtagene ciloleucel (Yescarta, Kite/Gilead, n=16, tisagenlecleucel (Kymriah, Novartis Pharma, n=5 and brexucabtagene autoleucel (KTE-X19, Tecartus, Kite/Gilead, n=1). One additional patient received allogeneic UCART19 (Servier). The median delay between CAR-T administration and the first vaccine (V1) was 401 days (d; range: 113-819). All patients but 2 were in complete remission at V1 and 3 were still on therapy (revlimid n=1, tafasitamab n=1, chemotherapy n=1).

After V1, antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested by the Roche Elecsys® assay at a median time of 29 d (range: 16-32) in 19 patients and 23 d (range:18-32) in controls. At that time, only 4/23 patients (21%) but all controls (100%) had a positive anti-spike antibody response (p<0.001). Among seropositive cases, median IgG titers were higher in controls (35.1 U/mL, range 2.2->250) than in patients (5.9 U/mL range 4.1-41.6, p=0.06). The highest IgG titer (>250) was obtained in 2 controls.

The median delay between V1 and the second vaccine (V2) was 28 d (range: 14-46) for patients and 23 d (range: 18-32) for controls. Among the 20 patients tested after V2, 17 had also been tested after V1 while 3 were tested only after V2. All controls were tested after V2. The second serology assay was performed at a median interval from V2 of 52 d (range: 21-99) for patients and 58 d (range: 32-71) for controls. This serology assay was positive in 6 patients (30%), while all controls (100%, p<0.001) had again a positive response. Three out of these 6 patients (15% of all patients) achieved the highest IgG titer according to the serology assay used. Among the 4 patients with positive antibody titers after V1, 3 remained positive including one reaching the highest IgG titer. The fourth patient has not yet received V2. Median IgG titers could not be compared with controls because various methods of detection were used after V2. However, all controls tested again by Roche Elecsys® displayed the highest IgG titer (>250) after V2. The two patients in relapse and treated by chemotherapy or tafasitamab did not develop antibodies after V2 conversely to the patient under maintenance by revlimid.

The delay between CAR-T infusion and vaccine did not influence the antibody response nor did the rate of lymphopenia as almost all patients remained under a lymphocyte threshold of 1x109/L.

Finally, with a median follow up from V1 of 77 d (range: 49-127) in patients and 81 d (range: 62-95) in controls, no COVID-19 infection has been documented in any of these participants.

Conclusion: This study shows that the administration of two doses of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine provides a low rate of seroconversion (30%) in recipients of CAR-T therapy. This is likely related to the profound B-cell depletion induced by this treatment precisely targeting CD19+ cells. Investigation of the development of specific T-cell responses in these individuals could provide more information about the efficacy of vaccination in this context.

Disclosures: Gastinne: Gilead/kyte: Honoraria; Takeda: Honoraria. Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Oncopeptides: Honoraria.

*signifies non-member of ASH