Vaccine titers in lymphoma patients receiving chimeric antigen receptor T-cell therapy.

Abstract

7555 Background: While CAR-T therapy is not myelo-ablative, patients with aggressive lymphoma treated with CD19 chimeric antigen receptor T cell therapy (CAR-T) are lymphodepleted and have prolonged B cell aplasia. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) is not known. We report the vaccine titers of patients treated with axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Methods: Retrospective chart review of adult lymphoma patients who received axi-cel from 9/2018 to 9/2020 for anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 (MO3) post CAR-T. Results: Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Strep pneumoniae (Strep PNA) (Table). Similar trends were seen whether patients had stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table). Compared to patients who had ASCT, those who did not had higher rate of positive titer for Strep PNA and lower rate for hepatitis B, Mumps, and VZV. The same trend for sero-positive rate were observed at MO3 post CAR-T. Patients with IgG<400 mg/dl received IVIG supplement for prophylaxis. Among the 23 patients who received IVIG, variable rate of conversion from negative to positive titers were seen for measles (1/2, 50%), mumps (2/3, 67%), rubella (2/3, 67%), varicella-zoster (VZV, 3/3, 100%), hepatitis A (6/6, 100%), hepatitis B (6/7, 86%) and Strep PNA (0/10, 0%). For patients who did not receive IVIG prophylaxis, there was one loss of seropositivity for Strep PNA (1/4, 25%). Conclusions: The presence of protective vaccine titers is variable for patients receiving CAR-T, regardless of recent ASCT. The loss of protective titers post CART was low. IVIG variably impacted vaccine titer status. Immunization remains important for patients with ASCT prior to CART, without completion of post ASCT immunization protocol. Further study is needed to inform the need for immunization and optimal timing post CART.[Table: see text]

Vaccine schedule recommendations and updates for patients with hematologic malignancy post‐hematopoietic cell transplant or CAR T‐cell therapy

“…Studies demonstrate a high rate of circulating IgG specific to tetanus (100% of patients) prior to CAR‐T infusion that was maintained, or comparable to healthy controls, at 3–20 months post‐infusion in 90%–100% of sampled patients 108,110,111,116,119,120 . Similarly, diphtheria antibodies were detected in 88%–95% of patients pre‐infusion, with similar seroprevalence maintained at post‐infusion follow‐up (median 3–20 months) 110,112 .…”

“…Available seroprevalence data is often adjunctive and exploratory; for example, comparing the prevalence of existing antibodies to vaccine‐preventable infections between CAR‐T treated patients and healthy controls to explore reasons for poor humoral response following SARS‐CoV‐2 vaccination 108,109 . Studies specifically aiming to characterize the effect of CAR‐T therapy on circulating pathogen‐specific IgGs are summarized in Table 2 110–115 . Studies differ in the timing of antibody measurement post‐CAR‐T, the exclusion or inclusion of patients receiving Ig replacement, and data are aggregated across mixed populations of leukemia, lymphoma, and myeloma patients 110–116 .…”

“…Within the limitations of a single study with pre‐infusion results, a high proportion of CAR‐T treated patients had demonstrable antibodies against VZV (82%) 111 . Post‐infusion serosurveys have demonstrated similar seroprevalence (87%–96%) 114,115 .…”

“… 108 , 109 Studies specifically aiming to characterize the effect of CAR‐T therapy on circulating pathogen‐specific IgGs are summarized in Table 2 . 110 , 111 , 112 , 113 , 114 , 115 Studies differ in the timing of antibody measurement post‐CAR‐T, the exclusion or inclusion of patients receiving Ig replacement, and data are aggregated across mixed populations of leukemia, lymphoma, and myeloma patients. 110 , 111 , 112 , 113 , 114 , 115 , 116 Data regarding seroprevalence in patients treated with bispecific or non‐CD19+ directed CAR‐T (e.g., B‐cell maturation antigen [BCMA]) therapies are lacking.…”

“… 110 , 111 , 112 , 113 , 114 , 115 Studies differ in the timing of antibody measurement post‐CAR‐T, the exclusion or inclusion of patients receiving Ig replacement, and data are aggregated across mixed populations of leukemia, lymphoma, and myeloma patients. 110 , 111 , 112 , 113 , 114 , 115 , 116 Data regarding seroprevalence in patients treated with bispecific or non‐CD19+ directed CAR‐T (e.g., B‐cell maturation antigen [BCMA]) therapies are lacking. 117 …”