Pregnancy and infant outcomes post–CD19-directed CAR-T therapy: Tisagenlecleucel (tisa-cel) and/or huCAR19 (CTL119).

7029 Background: Data on pregnancy post–CD19-directed CAR-T therapy for B-cell malignancies are limited (Ligon et al). There is a theoretical risk of cross-placental transmission of CAR-T cells in female patients (pts) during pregnancy. The impact of CAR-T on fertility, conception or pregnancy in pts is uncertain. High-dose chemotherapy/radiation has a high infertility risk (Lowe et al). Early use of CAR-T may increase the chance of fertility preservation. Methods: In this retrospective cohort analysis, a cumulative search in the Novartis Global Safety database for all CAR-T products, up to Jan 2025 was conducted using the Standard MedDRA Query: Pregnancy and neonatal topics (narrow). Transgene levels were monitored in clinical trial pts for all indications. Ongoing B-cell aplasia (BCA)/deficiency or intravenous immunoglobulin (IVIG) utilization was used as a surrogate marker for persistence of tisa-cel in pts with acute lymphoblastic leukemia (ALL). Pregnancy outcomes were collected via pregnancy and infant forms at birth and 3 and 12 month (mo), subject to reporter and/or patient consent. Results: Sixteen events of tisa-cel or CTL119 exposure during pregnancy were reported. Elective termination of pregnancy was noted in 2 cases. Pathology review of placental/fetal parts in one of these cases was unremarkable. One case did not have consent for follow-up (FU) and another one did not have newborn status. One pregnancy was ongoing with normal pregnancy to date and delivery expected in Q2 2025 (commercial tisa-cel). Eleven pregnancies resulted in live birth of 12 healthy infants (1 pregnancy with twins). Further details on these 11 pregnancies are provided in Table 1. Persistent CAR transgene levels in the clinical trial pts with ALL have shown concordance with the use of IVIG/ongoing BCA/deficiency (data not shown). One infant was enrolled to long-term FU and tested negative for huCAR19 transgene on day 7, though the number of B cells (80 cells/µL) and IgG levels were slightly low at birth. Among 3 commercial tisa-cel pts with reported pregnancies, 2 had ongoing IVIG during pregnancy and 1 at the time of delivery. Conclusions: Pregnancy and delivery of a healthy infant after CAR-T therapy is possible. The use of CAR-T therapy may improve chances of healthy pregnancy by avoiding the risks for infertility associated with high-dose chemotherapy and/or radiation. Capturing data on all pregnancies post CAR-T remains an important goal. Pregnancy and infant status post CAR-T. Pts 1 * 2* 3 4 5 6 7 8 9 10 11 Indication ALL ALL B-NHL FL Product Tisa-cel* CTL119 CTL019 Approx. age at conception (y), sex 22F 25M 20F 30M 29F 39M 25M 35M 28F 31F M Approx. time from CAR-T to conception 1y 3y 3y 6.5y 8y 1.5y 7mo 2.5y 6y 9mo 1y 7mo 1y 3mo Latest FU of healthy infant(s) 2y 4mo 22mo 18mo Birth 1y 21mo Birth (twins) Birth Birth 1y *Commercial tisa-cel. B-NHL, B-cell non-Hodgkin's lymphoma; FL, follicular lymphoma; y, years.