ASH Clinical News ACN_4.14_Full Issue_web | Page 119

Laboratory Abnormalities
Selected laboratory abnormalities worsening from baseline Grade 0-2 to Grade 3-4 are shown in Table 6.
Table 6. Grade 3 or 4 Laboratory Abnormalities occurring in > 10% of Patients Following KYMRIAH Infusion
in Adult r/r DLBCL Patients Based on CTCAE a N = 106
Laboratory Parameter Grade 3 or 4 (%)
Hematology
Lymphopenia
Neutropenia
Leukopenia
Anemia
Thrombocytopenia 94
81
77
58
54
Biochemistry
Hypophosphatemia
Hypokalemia
Hyponatremia 24
12
11
CTCAE = Common Terminology Criteria for Adverse Events version 4.03
a
6.2 Immunogenicity
In clinical studies, humoral immunogenicity of KYMRIAH was measured by determination of anti-murine
CAR19 antibodies (anti-mCAR19) in serum pre- and post-administration. The majority of patients, 86% in
ELIANA (Study 1) and 91.4% in JULIET (Study 2) tested positive for pre-dose anti-mCAR19 antibodies prior
to KYMRIAH infusion; Treatment induced anti-mCAR19 antibodies were detected in 5% of the patients in
JULIET. However, the preexisting and treatment-induced antibodies were not associated with an impact on
clinical response and did not have an impact on the initial expansion and persistence of KYMRIAH. Persis -
tence of KYMRIAH was similar between patients with positive post-infusion anti-mCAR19 antibodies com-
pared with patients with negative post-infusion anti-mCAR19 antibodies. There is no evidence that the
presence of pre-existing 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 develop-
mental 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 repro-
ductive 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 effec-
tive 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) in the full prescribing information]
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 differences in effi-
cacy or safety were observed between the different age subgroups or in comparison to the young adults in
the trial.
The safety and efficacy of KYMRIAH in pediatric patients with relapsed or refractory DLBCL has not been
established.
8.5 Geriatric Use
The safety and effectiveness of KYMRIAH have not been established in geriatric patients with r/r B-cell ALL.
Clinical studies of KYMRIAH did not include sufficient numbers of subjects aged 65 and over to determine
whether they respond differently from younger subjects.
Distributed by:
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936
© Novartis
T2018-67