General disorders and administration site conditions: multiple organ dysfunction syndrome (3%)  

Immune system disorders: graft versus host disease (1%)  

Investigations: activated partial thromboplastin time prolonged (6%)  

Nervous System: tremor (9%), dizziness (6%), seizure (3%), speech disordera (3%), motor dysfunctionb (1%)  

Respiratory, thoracic, and mediastinal disorders: respiratory distress (6%), respiratory failure (6%), acute respiratory distress syndrome (4%), oropharyngeal pain (6%)  

Metabolism and nutrition disorders: tumor lysis syndrome (6%)  

Vascular disorders: capillary leak syndrome (3%), thrombosis (3%)  

Eye disorders: Visual impairment (3%)  

Laboratory Abnormalities 

Selected laboratory abnormalities worsening from baseline Grade 0-2 to Grade 3-4 are shown in Table 3. 

Table 3. Selected Other Laboratory Abnormalities Worsening (> 10%) from Baseline Grade 0-2 to Grade 3-4 Following Treatment with KYMRIAH in Pediatric and Young Adult r/r B-cell ALL based on CTCAEa (N = 68) 

aCTCAE = Common Terminology Criteria for Adverse Events version 4.03 

Laboratory Abnormality Grade 3 or 4 (%) 

Increased Aspartate Aminotransferase 28 

Hypokalemia 27 

Increased Alanine Aminotransferase  21 

Increased bilirubin  21 

Hypophosphatemia 19 

All patients experienced neutropenia, anemia and thrombocytopenia. See Table 4 for the incidences of ≥ Grade 3 prolonged thrombocytopenia and prolonged neutropenia in responding patients. 

Table 4. Prolonged Cytopenias Following Treatment with KYMRIAH in Pediatric and Young Adult r/r B-cell ALL  

a ≥ Grade 3 observed within 14 days after Day 28 or Day 56 in responding patients 

Prolonged Cytopenia N = 52 (%) N = 52 (%) 

 Day 28 Day 56 

Prolonged neutropeniaa 40 17 

Prolonged thrombocytopeniaa 27 12 

Adult r/r Diffuse Large B-cell Lymphoma (DLBCL) 

In the JULIET study (Study 2) 106 adults with r/r DLBCL received a single intravenous dose of KYMRIAH [see Clinical Studies (14.2)]. The most common adverse reactions (incidence > 20%) were cytokine release syndrome, infections-pathogen unspecified, diarrhea, nausea, pyrexia, fatigue, hypotension, edema and headache.

The study population characteristics were: median age of 56 years (range: 22 to 76 years), 79% DLBCL; a median of 3 prior lines of therapy (range: 1-6), 49% had a prior autologous hematopoietic stem cell transplantation, and 33% had received prior radiation therapy. Ninety-nine patients (93%) received lymphodepleting chemotherapy prior to KYMRIAH, that included fludarabine (n = 77) or bendamustine (n = 22).

The adverse reactions with greater than or equal to 10% incidence for any Grade are summarized in Table 5 below.

Table 5. Selected Adverse Reactions Anytime After Infusion Reported in ≥ 10% Following Treatment with KYMRIAH in Adult r/r DLBCL (N = 106) 

aTachycardia includes tachycardia and sinus tachycardia. 

bFatigue includes fatigue and malaise. 

cEdema includes face edema, generalised edema, localized edema, edema peripheral, peripheral swelling.