6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling.

•: Infections [see Warnings and Precautions (5.1)]
•: Hyperglycemia [see Warnings and Precautions (5.2)]
•: Hypertension [see Warnings and Precautions (5.3)]
•: Non-infectious pneumonitis [see Warnings and Precautions (5.4)]
•: Neutropenia [see Warnings and Precautions (5.5)]
•: Severe cutaneous reactions [see Warnings and Precautions (5.6)]

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 the general patient population.

The safety data reflect exposure to ALIQOPA in 168 adults with follicular lymphoma and other hematologic malignancies treated with ALIQOPA 60 mg or 0.8 mg/kg equivalent in clinical trials. The median duration of treatment was 22 weeks (range 1 to 206 weeks).

Serious adverse reactions were reported in 44 (26%) patients. The most frequent serious adverse reactions that occurred were pneumonia (8%), pneumonitis (5%) and hyperglycemia (5%). The most common adverse reactions (≥20%) were hyperglycemia, diarrhea, decreased general strength and energy, hypertension, leukopenia, neutropenia, nausea, lower respiratory tract infections, and thrombocytopenia.

Adverse reactions resulted in dose reduction in 36 (21%) and discontinuation in 27 (16%) patients. The most common reasons for dose reduction were hyperglycemia (7%), neutropenia (5%), and hypertension (5%). The most common reasons for drug discontinuation were pneumonitis (2%) and hyperglycemia (2%).

Table 2 provides the adverse reactions occurring in at least 10% of patients receiving ALIQOPA monotherapy, and Table 3 provides the treatment-emergent laboratory abnormalities in ≥20% of patients and ≥4% of Grade ≥3 treated with ALIQOPA.

Table 2: Adverse Reactions Reported in ≥10% of Patients with Follicular Lymphoma and Other Hematological Malignancies Treated with ALIQOPA
ADVERSE REACTIONS	ALIQOPA N = 168
ADVERSE REACTIONS	Any Grade n (%)	Grade 3 n (%)	Grade 4 n (%)
Metabolism and nutrition disorders
Hyperglycemia	90 (54%)	56 (33%)	10 (6%)
Blood and lymphatic system disorders
Leukopenia	61 (36%)	20 (12%)	26 (15%)
Neutropenia (including febrile neutropenia)	53 (32%)	16 (10%)	26 (15%)
Thrombocytopenia	37 (22%)	12 (7%)	2 (1%)
General disorders and administration site conditions
Decreased general strength and energy (includes fatigue and asthenia)	61 (36%)	6 (4%)	0
Gastrointestinal disorders
Diarrhea	60 (36%)	8 (5%)	0
Nausea	43 (26%)	1 (<1%)	0
Stomatitis (includes oropharyngeal erosion and ulcer, oral pain)	24 (14%)	3 (2%)	0
Vomiting	21 (13%)	0	0
Vascular disorders
Hypertension (includes secondary hypertension)	59 (35%)	46 (27%)	0
Infections
Lower respiratory tract infections (includes pneumonia, pneumonia bacterial, pneumonia pneumococcal, pneumonia fungal, pneumonia viral, pneumocystis jiroveci pneumonia, bronchopulmonary aspergillosis and lung infection)	35 (21%)	20 (12%)	3 (2%)
Skin and subcutaneous tissue disorders
Rash (includes exfoliative skin reactions)	26 (15%)	2 (1%)	1 (<1%)

Additional adverse drug reactions reported at a frequency of <10% in patients with follicular lymphoma and other hematologic malignancies include pneumonitis (9%), mucosal inflammation (8%), and paresthesia and dysesthesia (7%).

Table 3: Treatment-emergent Laboratory Abnormalities in ≥20% of Patients and ≥4% of Grade ≥3 Treated with ALIQOPA
Laboratory Parameter	ALIQOPA N = 168*
Laboratory Parameter	Any Grade** n (%)	Grade 3** n (%)	Grade 4** n (%)
Hematology abnormalities
Decreased hemoglobin	130 (78%)	7 (4%)	0
Lymphocyte count decreased	126 (78%)	43 (27%)	4 (2%)
White blood cell decreased	118 (71%)	30 (18%)	3 (2%)
Platelet count decreased	109 (65%)	11 (7%)	3 (2%)
Neutrophil count decreased	104 (63%)	20 (12%)	25 (15%)
Serum chemistry abnormalities
Hyperglycemia	160 (95%)	72 (43%)	9 (5%)
Hypertriglyceridemia	74 (58%)	6 (5%)	0
Hypophosphatemia	72 (44%)	24 (15%)	0
Hyperuricemia	42 (25%)	40 (24%)	2 (1%)
Serum lipase increased	34 (21%)	11 (7%)	2 (1%)

*Denominator for each laboratory parameter may vary based on number of patients with specific numeric laboratory values available.

**NCI-CTCAE v4.03