•Cytokine Release Syndrome [see Warnings and Precautions (5.1)]
•Neurological Toxicities [see Warnings and Precautions (5.2)]
•Infections [see Warnings and Precautions (5.3)]
•Tumor Lysis Syndrome [see Warnings and Precautions (5.4)]
•Neutropenia and Febrile Neutropenia [see Warnings and Precautions (5.5)]
•Effects on Ability to Drive and Use Machines [see Warnings and Precautions (5.6)]
•Elevated Liver Enzymes [see Warnings and Precautions (5.7)]
•Leukoencephalopathy [see Warnings and Precautions (5.8)]
•Preparation and Administration Errors [see Warnings and Precautions (5.9)]

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 this section reflect exposure to BLINCYTO in clinical trials in which 212 patients with relapsed or refractory ALL received up to 28 mcg/day. All patients received at least one dose of BLINCYTO. The median age of the study population was 37 years (range: 18 to 79 years), 63% were male, 79% were White, 3% were Asian, and 3% were Black or African American.

The most common adverse reactions (≥ 20%) were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), and constipation (20%).

Serious adverse reactions were reported in 65% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, pneumonia, sepsis, neutropenia, device-related infection, tremor, encephalopathy, infection, overdose, confusion, Staphylococcal bacteremia, and headache.

Adverse reactions of Grade 3 or higher were reported in 80% of patients. Discontinuation of therapy due to adverse reactions occurred in 18% of patients treated with BLINCYTO. The adverse reactions reported most frequently as the reason for discontinuation of treatment included encephalopathy and sepsis. Fatal adverse events occurred in 15% of patients. The majority of these events were infections. No fatal adverse events occurred on treatment among patients in remission.

The adverse reactions with ≥ 10% incidence for any grade or ≥ 5% incidence for Grade 3 or higher are summarized in Table 2.

Table 2. Adverse Reactions With ≥ 10% Incidence for Any Grade or ≥ 5% Incidence for Grade 3 or Higher (N = 212)  Adverse Reaction
 Any Grade*
(%)
 Grade 3 or
Higher*
(%)
 
*
Grading based on NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

†
Diarrhea includes the following terms: colitis, diarrhea, enteritis, and neutropenic colitis.

‡
Tremor includes the following terms: resting tremor and tremor.
§
Dyspnea includes the following terms: acute respiratory failure, bronchial hyperactivity, bronchospasm, dyspnea, dyspnea exertional, respiratory distress, respiratory failure, and wheezing.

¶
Rash includes the following terms: erythema, rash, erythematous rash, generalized rash, macular r