Impact of Anti-CD19 CAR-T Axicabtagene Ciloleucel on Vaccine Titers of DTaP and MMR

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed/refractory B-cell lymphoid malignancies. Axicabtagene ciloleucel (axi-cel), an anti-CD19 CAR-T not only targets the malignant B-cell, but can potentially also target and eliminate normal B-cells. This can interfere with the normal B-cell repertoire, compromising host humoral immunity such as decreased titers of common vaccines (DTaP, MMR). To assess if this was a clinically significant problem, we evaluated all recipients of axi-cel at our center between 6/2018 through 7/2019.

Patients and methods: For patients who received commercial axi-cel, humoral immunity was evaluated both quantitatively [absolute lymphocyte count (ALC)] as well as qualitatively by serology titers [IgG antibodies (Abs)] for diphtheria, tetanus, pertussis, measles, mumps, and rubella, and total Immunoglobulin G (IgG) levels. Data was collected within 30 days prior to CAR-T infusion, then at day +30 and between days +60 and +100 after CAR-T infusion.

Results: We identified 10 patients (males = 5, 50%), with a median age of 49.9 years (range 30-65) who received commercial axi-cel during the study period. Patient characteristics and indications for CAR-T therapy are shown in Table 1; the cohort represented a heavily pre-treated aggressive B-cell lymphoma patient population. Baseline information on antibody (Ab) titers was available in 8 patients. At baseline, all patients had positive tetanus IgG Abs (≥0.01 IU/mL), 7 had positive diphtheria IgG Abs (≥0.01 IU/mL), 6 had positive measles IgG Abs (≥ 1.1 AI), 5 had positive rubella IgG Abs (≥ 1.0 AI), 3 had positive mumps IgG Abs (≥ 1.1 AI). None of the patients had a positive pertussis IgG Abs (≥100 IU/mL). At follow-up, all patients with positive Ab at baseline maintained titers in the positive range at day +30 and between days +60 and +100 (Figure 1). None of the patients demonstrated a clinically meaningful decrease in Abs titers, despite a drop in ALC and IgG levels (table 2).

Conclusions: Albeit a small sample size, IgG Ab titers for diphtheria, tetanus, measles, mumps, and rubella did not appear to be affected by axi-cel at a short interval follow-up after infusion (up to day +100). We plan to extend this analysis in a larger cohort with a longer-term prospective follow-up to validate our findings, especially in light of dropping absolute lymphocyte counts and IgG levels.

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