ASH Clinical News ACN_4.14_Full Issue_web | Page 116

IMPORTANT SAFETY INFORMATION (continued)
Serious Infections (continued): Febrile neutropenia
(≥ grade 3) was also observed in 37% of patients with
r/r ALL and 17% of patients with r/r DLBCL after KYMRIAH
infusion and may be concurrent with CRS. In the event of
febrile neutropenia, evaluate for infection and manage
with broad spectrum antibiotics, fluids, and other
supportive care as medically indicated.
Hepatitis B virus (HBV) reactivation, in some cases
resulting in fulminant hepatitis, hepatic failure, and
death, can occur in patients treated with drugs directed
against B cells. Perform screening for HBV, HCV, and HIV
in accordance with clinical guidelines before cell collection
for manufacturing.
Prolonged Cytopenias: Patients may exhibit cytopenias
for several weeks following lymphodepleting
chemotherapy and KYMRIAH infusion. In patients with
r/r ALL, ≥ grade 3 cytopenias not resolved by Day 28
following KYMRIAH treatment included neutropenia (40%)
and thrombocytopenia (27%) among 52 responding
patients. At 56 days following KYMRIAH, 17% and
12% of responding patients had ≥ grade 3 neutropenia or
thrombocytopenia respectively. In patients with r/r DLBCL,
grade ≥3 cytopenias not resolved by Day 28 following
KYMRIAH treatment included thrombocytopenia (40%)
and neutropenia (25%) among 106 treated patients.
Prolonged neutropenia has been associated with increased
risk of infection. Myeloid growth factors, particularly
GM-CSF, are not recommended during the first 3 weeks
after KYMRIAH infusion or until CRS has resolved.
Hypogammaglobulinemia: Hypogammaglobulinemia
and agammaglobulinemia (IgG) related to B-cell aplasia
can occur in patients with a complete remission after
KYMRIAH infusion. Hypogammaglobulinemia was reported
in 43% of patients with r/r ALL and 14% of patients with
r/r DLBCL. Monitor immunoglobulin levels after treatment
with KYMRIAH and manage using infection precautions,
antibiotic prophylaxis, and immunoglobulin replacement
standard guidelines.
The safety of immunization with live viral vaccines during
or following KYMRIAH treatment has not been studied.
Vaccination with live virus vaccines is not recommended
for at least 6 weeks prior to the start of lymphodepleting
chemotherapy, during KYMRIAH treatment, and until
immune recovery following treatment with KYMRIAH.
Pregnant women who have received KYMRIAH may have
hypogammaglobulinemia. Assess immunoglobulin levels
in newborns of mothers treated with KYMRIAH.
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936-1080
© 2018 Novartis
Secondary Malignancies: Patients treated with KYMRIAH
may develop secondary malignancies or recurrence of
their cancer. Monitor lifelong for secondary malignancies.
If a secondary malignancy occurs, call 1-844-4KYMRIAH to
obtain instructions on patient samples to collect for testing.
Effects on Ability to Drive and Use Machines: Due to the
potential for neurological events, including altered mental
status or seizures, patients receiving KYMRIAH are at risk
for altered or decreased consciousness or coordination in
the 8 weeks following infusion. Advise patients to refrain
from driving and engaging in hazardous occupations or
activities, such as operating heavy or potentially dangerous
machinery, during this initial period.
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 tests (NATs)
may yield false positive results in patients who have
received KYMRIAH.
Pregnancy, Lactation, Females and Males
of Reproductive Potential
No data are available of KYMRIAH use in pregnant or
lactating women. Therefore, KYMRIAH is not recommended
for women who are pregnant or breastfeeding. Pregnancy
after KYMRIAH administration should be discussed with
the treating physician. Pregnancy status of females of
reproductive potential should be verified with a pregnancy
test prior to starting treatment with KYMRIAH. Report
pregnancies to Novartis Pharmaceuticals Corporation at
1-888-669-6682.
Adverse Reactions
The most common adverse reactions (>20%) reported
in patients with r/r ALL were cytokine release syndrome,
hypogammaglobulinemia, infections-pathogen
unspecified, pyrexia, decreased appetite, headache,
encephalopathy, hypotension, bleeding episodes,
tachycardia, nausea, diarrhea, vomiting, viral infectious
disorders, hypoxia, fatigue, acute kidney injury, edema,
cough, and delirium.
The most common adverse reactions (>20%) reported in
patients with r/r DLBCL were cytokine release syndrome,
infections-pathogen unspecified, pyrexia, diarrhea, nausea,
fatigue, hypotension, edema, and headache.
Please see additional Important Safety Information
and Brief Summary of Prescribing Information
for KYMRIAH, including Boxed WARNING, on the
following pages.
Printed in USA
10/18
KYD-1198765