Gazyva (Obinutuzumab) Side Effects
Gazyva (obinutuzumab) commonly causes infusion-related reactions, neutropenia, and thrombocytopenia as its most significant side effects, with infusion reactions occurring in up to 72% of patients and severe neutropenia in 35% of patients. 1
Common Side Effects
Hematologic Toxicities
- Neutropenia: Occurs in 35-53% of patients (Grade 3-4 in 35-49%) 2, 1
- Thrombocytopenia: Occurs in 11-14% of patients (Grade 3-4 in 7-11%) 2, 1
- Lymphopenia: Occurs in up to 97% of patients (Grade 3-4 in 92%) 1
- Leukopenia: Occurs in up to 84% of patients (Grade 3-4 in 47%) 1
- Anemia: Occurs in up to 39% of patients (Grade 3-4 in 10%) 1
Infusion-Related Reactions
- Incidence: 67-72% of patients (Grade 3-4 in 11-21%) 2, 1
- Timing: Most common during first infusion, typically within 90 minutes 3
- Symptoms: Throat discomfort, breathing difficulty, skin rash, chills, fever 3
- Management: Slowing or temporarily halting infusion; premedication with corticosteroids, antihistamines, and acetaminophen 4, 5
Infections
Gastrointestinal and Hepatic
- Constipation: 32% 1
- Diarrhea: 30% 1
- Nausea/vomiting: Common during infusions 1
- Liver enzyme elevations:
Other Common Side Effects
- Fatigue: 40% 1
- Cough: 31-35% 1
- Musculoskeletal pain: 28% 1
- Headache: 18% 1
- Pyrexia: 19% 1
- Arthralgia: 12-16% 1
- Rash/pruritus: 11-17% 1
- Decreased appetite: 14% 1
- Insomnia: 15% 1
Severe or Concerning Side Effects
IgM Flare
- Occurs in patients with Waldenström's macroglobulinemia
- May require plasmapheresis to prevent symptomatic hyperviscosity 6
Electrolyte Abnormalities
- Hypocalcemia: 37-39% 1
- Hyponatremia: 26% 1
- Hypokalemia: 14% 1
- Hyperkalemia: 20% 1
- Hypophosphatemia: 41% 1
Rare but Serious Adverse Events
- Febrile neutropenia: 6% 1
- Cardiac events: Higher risk compared to rituximab 7
- Progressive multifocal leukoencephalopathy (PML): Rare but potentially fatal
Risk Factors and Monitoring
High-Risk Patients
- Elderly patients
- Patients with significant comorbidities
- Patients with high tumor burden
- Patients with high baseline IgM levels
Monitoring Recommendations
- Complete blood counts: Regular monitoring before each treatment cycle 2
- Liver function tests: Before and during treatment 1
- Electrolytes: Regular monitoring during treatment 1
- Infection surveillance: Throughout treatment and follow-up period 2
Management of Side Effects
Infusion Reactions
Premedication:
- Corticosteroids (methylprednisolone 125 mg has shown better results than 80 mg) 5
- Antihistamines
- Acetaminophen
During infusion:
- Slow or temporarily halt infusion if reactions occur
- Resume at lower rate when symptoms resolve
- Severe reactions may require permanent discontinuation
Neutropenia and Infections
- Prophylactic antibiotics for high-risk patients
- Growth factor support may be considered
- Dose modifications or delays based on neutrophil counts
Thrombocytopenia
- Monitor platelet counts before each treatment cycle
- Dose modifications or delays for severe thrombocytopenia
Comparison with Other Anti-CD20 Antibodies
Obinutuzumab has shown higher efficacy but also increased toxicity compared to rituximab:
- Higher rates of Grade 3-4 adverse events (RR 1.15) 7
- Significantly higher rates of thrombocytopenia (RR 2.8) 7
- Significantly higher rates of infusion-related reactions (RR 2.8) 7
- Higher rates of cardiac events (RR 1.65) 7
Clinical Considerations
When initiating Gazyva therapy, careful attention to premedication and close monitoring during the first infusion are essential to manage the high risk of infusion reactions. Regular blood count monitoring is crucial throughout treatment to detect and manage hematologic toxicities early.