iated with an impact on clinical response and did not have an impact on the initial expansion and persistence of KYMRIAH. Persistence of KYMRIAH was similar between patients with positive post-infusion anti-mCAR19 antibodies compared with patients with negative post-infusion anti-mCAR19 antibodies. There is no evidence that the presence of preexisting and treatment-induced anti-mCAR19 antibodies impact the safety or effectiveness of KYMRIAH.
T cell immunogenicity responses were not observed in adult r/r DLBCL patients.
7 DRUG INTERACTIONS
HIV and the lentivirus used to make KYMRIAH have limited, short spans of identical genetic material (RNA). Therefore, some commercial HIV nucleic acid test (NATs) tests may yield false-positive results in patients who have received KYMRIAH.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data with KYMRIAH use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with KYMRIAH to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if KYMRIAH has the potential to be transferred to the fetus. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia. Therefore, KYMRIAH is not recommended for women who are pregnant, and pregnancy after KYMRIAH administration should be discussed with the treating physician. Report pregnancies to Novartis Pharmaceuticals Corporation at 1-888-669-6682.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
8.2 Lactation
Risk Summary
There is no information regarding the presence of KYMRIAH in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for KYMRIAH and any potential adverse effects on the breastfed infant from KYMRIAH or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Pregnancy status of females with reproductive potential should be verified. Sexually-active females of reproductive potential should have a pregnancy test prior to starting treatment with KYMRIAH.
Contraception
See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy.
There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with KYMRIAH.
Infertility
There are no data on the effect of KYMRIAH on fertility.
8.4 Pediatric Use
The safety and efficacy of KYMRIAH have been established in pediatric patients with r/r B-cell ALL. Use of KYMRIAH is supported by a single-arm trial [see Clinical Studies (14.1)] that included 52 pediatric patients with r/r B-cell precursor ALL in the following age groups: 33 children (age 3 years to less than 12 years) and 19 adolescents (age 12 years to less than 17 years). No di
