"The U.S. Food and Drug Administration today approved Gazyva (obinutuzumab) for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).
CLL is a blood and bone ma"...
The following adverse reactions are discussed in greater detail in other sections of the label:
- Hepatitis B reactivation [see WARNINGS AND PRECAUTIONS]
- Progressive multifocal leukoencephalopathy [see WARNINGS AND PRECAUTIONS]
- Infusion reactions [see WARNINGS AND PRECAUTIONS]
- Tumor lysis syndrome [see WARNINGS AND PRECAUTIONS]
- Infections [see WARNINGS AND PRECAUTIONS]
- Neutropenia [see WARNINGS AND PRECAUTIONS]
- Thrombocytopenia [see WARNINGS AND PRECAUTIONS]
The most common adverse reactions (incidence ≥ 10%) were: infusion reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, and musculoskeletal disorders.
Clinical Trial 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 data described in Tables 3 and 4 below are based on a total of 356 previously untreated patients with CLL during treatment with GAZYVA in combination with chlorambucil or with chlorambucil alone. Patients received three 1000 mg doses of GAZYVA on the first cycle and a single dose of 1000 mg once every 28 days for 5 additional cycles in combination with chlorambucil (6 cycles of 28 days each in total). In the last 45 patients enrolled, the first dose of GAZYVA was split between day 1 (100 mg) and day 2 (900 mg) [see DOSAGE AND ADMINISTRATION]. In total, 81% of patients received all 6 cycles (of 28 days each) of GAZYVA based therapy.
Table 3 : Summary of Adverse Reactions Reported
with ≥ 5% Incidence and ≥ 2% Greater in the GAZYVA Treated
|Adverse Reactions (MedDRAa)
System Organ Class
|GAZYVA + Chlorambucil
n = 240
n = 116
|All Grades %||Grades 3-4b %||All Grades %||Grades 3-4b %|
|Injury, Poisoning and Procedural Complications|
|Infusion related reactions||69||21||0||0|
|Blood and lymphatic system disordersc|
|General disorders and administration site conditions|
|Respiratory, thoracic and mediastinal disorders|
|aMedDRA coded adverse reactions as reported by
b No Grade 5 adverse reactions have been observed with a difference of ≥ 2% between the treatment arms.
c Adverse events reported under 'Blood and lymphatic system disorders' reflect those reported by investigator as clinically significant.
Table 4 : Post-Baseline Laboratory Abnormalities by
CTCAE Grade with ≥ 5% Incidence and ≥ 2 % Greater in
the GAZYVA Treated Arm
|Investigations||GAZYVA + Chlorambucil
n = 240
n = 116
|All Grades %||Grades 3-4 %||All Grades %||Grades 3-4 %|
|AST (SGOT increased)||28||< 1||12||0|
|Creatinine increased||28||< 1||18||< 1|
|ALT (SGPT increased)||25||< 1||14||0|
|Hypoalbuminemia||22||< 1||14||< 1|
|Alkaline Phosphatase increased||16||0||11||0|
The incidence of infusion reactions was 69% with the first infusion of GAZYVA. The incidence of Grade 3 or 4 infusion reactions was 21% with 8% of patients discontinuing therapy. The incidence of reactions with subsequent infusions was 3% with the second 1000 mg and < 1% thereafter. No Grade 3 or 4 infusion reactions were reported beyond the first 1000 mg infused.
Of the first 53 patients receiving GAZYVA on the trial, 47 (89%) experienced an infusion reaction. After this experience, study protocol modifications were made to require premedication with a corticosteroid, anti-histamine, and acetaminophen. The first dose was also divided into two infusions (100 mg on day 1 and 900 mg on day 2). For the 45 patients for whom these mitigation measures were implemented, 21 patients (47%) experienced a reaction with the first 1000 mg and < 2% thereafter [see DOSAGE AND ADMINISTRATION].
The incidence of neutropenia reported as an adverse reaction was 40% in the GAZYVA treated arm and 18% in the chlorambucil alone arm with the incidence of serious adverse events being 1% and 0%, respectively (Table 3). Cases of late onset neutropenia (occurring 28 days after completion of treatment or later) were 16% in the GAZYVA treated arm and 12% in the chlorambucil alone arm.
The incidence of infections was similar between arms. Thirty-eight percent of patients in the GAZYVA treated arm experienced an infection, 9% were Grade 3–4 and none were fatal.
The incidence of thrombocytopenia reported as an adverse reaction was 15% in the GAZYVA treated arm and 7% in the chlorambucil alone arm (Table 3). Five percent of patients in the GAZYVA treated arm experienced acute thrombocytopenia (occurring within 24 hours after the GAZYVA infusion). The number of fatal hemorrhagic events was similar between the treatment arms, with 4 in the GAZYVA treated arm. However, all fatal hemorrhagic events in patients treated with GAZYVA occurred in Cycle 1.
Tumor Lysis Syndrome
The incidence of Grade 3 or 4 tumor lysis syndrome was 2% in the GAZYVA treated arm versus 0% in the chlorambucil arm.
Adverse events related to musculoskeletal disorders, including pain (System Organ Class) have been reported with GAZYVA with higher incidence than in the comparator arm (17% vs. 13%).
Serum samples from patients with previously untreated CLL were tested during and after treatment for antibodies to GAZYVA. Approximately 13% (9/70) of GAZYVA treated patients tested positive for anti-GAZYVA antibodies at one or more time points during the 12 month follow-up period. Neutralizing activity of anti-GAZYVA antibodies has not been assessed.
Immunogenicity data are highly dependent on the sensitivity and specificity of the test methods used. Additionally, the observed incidence of a positive result in a test method may be influenced by several factors, including sample handling, timing of sample collection, drug interference, concomitant medication and the underlying disease. Therefore, comparison of the incidence of antibodies to GAZYVA with the incidence of antibodies to other products may be misleading. Clinical significance of anti-GAZYVA antibodies is not known.
Additional Clinical Trial Experience
Worsening of pre-existing cardiac conditions: Fatal cardiac events have been reported in patients treated with GAZYVA.
Hepatitis B reactivation: Hepatitis B virus reactivation has been reported with GAZYVA [see WARNINGS AND PRECAUTIONS].
Read the Gazyva (obinutuzumab injection) Side Effects Center for a complete guide to possible side effects
No formal drug interaction studies have been conducted with GAZYVA.
Last reviewed on RxList: 7/14/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Gazyva Information
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