Vaccine Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy
Authors: Bansal Radhika , Vergidis Paschalis , Tosh Pritish K , Wilson John , Hathcock Matthew , Khurana Arushi , Bennani N. Nora , Paludo Jonas , Villasboas Jose C. , Wang Yucai , Ansell Stephen M. , Johnston Patrick B. , Freeman Catherine , Lin Yi 
Published: November 2021

Abstract
Background: While CD19 chimeric antigen receptor T cell therapy (CAR-T) therapy does not use myeloablative chemotherapy, patients with aggressive lymphoma treated with CAR-T are immunosuppressed from lymphodepletion chemotherapy, and prolonged B cell aplasia and hypogammaglobulinemia from CAR-T. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) has not been formally studied. We report the vaccine titers of patients treated with CAR-T at Mayo Clinic, Rochester.
Methods: We conducted a retrospective chart review of patients who received CAR-T from 9/2018 to 4/2021 for treatment of aggressive lymphoma at Mayo Clinic, Rochester. Data was collected on anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 post CAR-T. Clinical assays for vaccine titers were used for patient assessment and threshold for clinical assays was used to define antibody titer as positive or negative.
Results: In our cohort of 87 CAR-T patients, 83 (94%) patients were infused with axicabtagene ciloleucel, 4 (5%) patients received brexucabtagene autoleucel and 1 (1%) received tisagenlecleucel. Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Streptococcus pneumoniae (Strep PNA). Similar trends were seen whether patients had autologous stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table 1).
At 3 months post CAR-T, overall seropositivity rates were similar when compared to pre-CAR-T levels for the prior transplant and no prior transplant group. For patients who had received intravenous immunoglobulin (IVIG) supplement prophylactically (for IVIG&lt;400 mg/dl), seropositivity rate for Strep PNA remained zero (Table 1). Among the 30 patients who received IVIG, variable rate of conversion from negative to positive titers were seen for measles (1/2, 50%), mumps (3/5, 60%), rubella (3/4, 75%), varicella-zoster (VZV, 4/4, 100%), hepatitis A (8/9, 89%) and hepatitis B (10/12, 83%).
For patients who did not receive IVIG prophylaxis after CAR-T, seropositivity rate for hepatitis A and B was low. In addition, some of these patients had a loss of seropositivity for Strep PNA (2/5, 40%) and hepatitis A (1/4, 25%).
Conclusion: The presence of protective vaccine titers is variable for patients receiving CAR-T therapy, regardless of recent ASCT. The loss of protective titers post CAR-T was low. The need for immunization post CAR-T may remain important regardless of transplant status prior to CAR-T. Prophylactic IVIG does not confer complete immunization protection. Optimal timing for immunization post CAR-T is probably unknown and may need to be considered earlier for patients not on prophylactic IVIG. Further study with longer follow-up is needed to inform the need for immunization and optimal timing post CAR-T.
Figure 1 Figure 1.

Disclosures
Bennani: Kymera: Other: Advisory Board; Vividion: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board. Paludo: Karyopharm: Research Funding. Wang: LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; Genentech: Research Funding; Novartis: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; InnoCare: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Lin: Sorrento: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Vineti: Consultancy; Juno: Consultancy; Legend: Consultancy; Gamida Cell: Consultancy; Merck: Research Funding; Bluebird Bio: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.