Cytokine Release Syndrome [see Warnings and Precautions (5.1)] 

Neurological Toxicities [see Warnings and Precautions (5.2)] 

Infections and Febrile Neutropenia [see Warnings and Precautions (5.5)] 

Prolonged Cytopenias [see Warnings and Precautions (5.6)] 

Hypogammaglobulinemia [see Warnings and Precautions (5.7)] 

6.1     Clinical Trials Experience 

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described in the WARNINGS AND PRECAUTIONS and in this section reflect exposure to KYMRIAH in two non-randomized, single-arm studies in which 68 pediatric and young adult patients with relapsed/refractory (r/r) B-cell ALL (ELIANA Study) and 106 adults with r/r diffuse large B-cell lymphoma (JULIET Study) received a single dose of CAR-positive viable T cells.

Pediatric and Young Adult r/r B-cell Acute Lymphoblastic Leukemia (ALL) (up to 25 years of age) 

Based on a recommended dose which was weight-based, all 68 patients in the ELIANA study (Study 1) received a single intravenous dose of KYMRIAH [see Clinical Studies (14.1)]. The most common adverse reactions (> 20%) were cytokine release syndrome (79%), hypogammaglobulinemia (43%), infections-pathogen unspecified (41%), pyrexia (40%), decreased appetite (37%), headache (37%), encephalopathy (34%), hypotension (31%), bleeding episodes (31%), tachycardia (26%), nausea (26%), diarrhea (26%), vomiting (26%), viral infectious disorders (26%), hypoxia (24%), fatigue (25%), acute kidney injury (24%), edema (21%), cough (21%), and delirium (21%).

The adverse reactions with greater or equal to 10% incidence for any Grade are summarized in Table 2.

Table 2. Selected Adverse Reactions Anytime After Infusion (≥ 10%) Following Treatment with KYMRIAH in Pediatric and Young Adult r/r B-cell ALL (N = 68) 

aTachycardia includes tachycardia and sinus tachycardia. 

bAbdominal pain includes abdominal pain, abdominal pain upper. 

cFatigue includes fatigue and malaise. 

dEdema includes face edema, generalised edema, localised edema, edema peripheral. 

ePain includes pain and pain in the extremity.  

fHypogammaglobulinemia includes hypogammaglobulinemia, immunoglobulins decreased, blood immunoglobulin G decreased, blood immunoglobulin A decreased, blood immunoglobulin M decreased. 

gHeadache includes headache and migraine. 

hEncephalopathy includes encephalopathy, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, lethargy, mental status changes, somnolence, and automatism. 

iDelirium includes delirium, agitation, hallucination, hallucination visual, irritability, restlessness. 

jSleep disorders includes sleep disorder, insomnia and nightmare. 

kAcute kidney injury includes acute kidney injury, anuria, azotemia, renal failure, renal tubular dysfunction, renal tubular necrosis, and blood creatinine increased. 

lCough includes cough and productive cough.