Obinutuzumab (Gazyva) and rituximab (Rituxan) are monoclonal antibody medications used to treat specific blood cancers, such as chronic lymphocytic leukemia (CLL) and follicular lymphoma. While both target cancerous B-cells, they differ in how they work, their effectiveness, and patient experience. This article compares these therapies.
Mechanism of Action
Both obinutuzumab and rituximab target the CD20 protein on B-cells, including cancerous ones, to help eliminate malignant cells.
Rituximab is a Type I anti-CD20 antibody. It primarily eliminates B-cells by activating the complement system, leading to Complement-Dependent Cytotoxicity (CDC). Rituximab also flags B-cells for destruction by other immune cells, a process called Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC). Additionally, it can directly trigger programmed cell death, or apoptosis.
Obinutuzumab is a glycoengineered Type II anti-CD20 antibody. Glycoengineering modifies the antibody’s sugar molecules, enhancing its binding to FcγRIIIa receptors on immune effector cells like natural killer (NK) cells. This stronger binding leads to enhanced ADCC, making it more effective at recruiting immune cells to destroy cancerous B-cells. Obinutuzumab is also more potent at inducing direct cell death than rituximab, while having reduced capacity to activate the complement system.
Clinical Efficacy and Approved Uses
The CLL11 study compared obinutuzumab plus chlorambucil to rituximab plus chlorambucil in previously untreated CLL patients with co-existing medical conditions. Obinutuzumab improved progression-free survival (PFS), with a median PFS of 28.9 months compared to 15.7 months for rituximab.
The CLL11 trial also showed obinutuzumab extended overall survival (OS) in these patients, with the median OS not reached in the obinutuzumab arm versus 73.1 months for rituximab. Time to next treatment was also longer with obinutuzumab. These results established obinutuzumab as a preferred first-line treatment for this patient group.
In follicular lymphoma (FL), the GALLIUM trial compared obinutuzumab-based immunochemotherapy with rituximab-based immunochemotherapy in previously untreated patients. Obinutuzumab prolonged PFS, showing a 7-year PFS rate of approximately 62.9% compared to 51.8% for rituximab. Despite the PFS benefit, overall survival was similar between the two treatment arms.
Rituximab is approved for non-Hodgkin lymphoma (NHL), including relapsed or refractory low-grade or follicular CD20-positive B-cell NHL, and previously untreated and treated CD20-positive CLL in combination with chemotherapy.
Obinutuzumab is approved for previously untreated CLL in combination with chlorambucil. It is also used for previously untreated bulky stage II, III, or IV follicular lymphoma in combination with chemotherapy, followed by obinutuzumab monotherapy, and for relapsed or refractory follicular lymphoma in combination with bendamustine, followed by obinutuzumab monotherapy.
Comparing Safety and Side Effect Profiles
Both obinutuzumab and rituximab can cause side effects, with differences in their safety profiles.
Infusion-related reactions (IRRs) are common with both, typically occurring during or shortly after infusion. Obinutuzumab has a higher incidence and severity of IRRs, particularly during the first infusion. Any-grade IRRs can occur in over 60% of patients with obinutuzumab compared to around 50% for rituximab, and severe (Grade 3 or higher) IRRs are more frequent with obinutuzumab.
These reactions often manifest as fever, chills, nausea, vomiting, or breathing difficulties, and are usually manageable with pre-medications like acetaminophen, antihistamines, and corticosteroids. Patients with pre-existing heart or lung conditions may experience more severe reactions and require closer monitoring.
Hematologic side effects are also observed with both drugs. Obinutuzumab is linked to a higher rate of Grade 3-4 neutropenia and a higher risk of Grade 3-4 thrombocytopenia. Neutropenia can increase the risk of serious infections, while thrombocytopenia may lead to bleeding events.
The risk of infection is higher with obinutuzumab due to its more potent B-cell depletion. Patients with existing chronic infections or compromised kidney function may be at increased risk. Regular blood tests monitor these counts and manage complications.
Administration and Patient Experience
Both obinutuzumab and rituximab are administered intravenously in a clinic or infusion center setting.
For obinutuzumab, the first dose in Cycle 1 is often split to help manage infusion-related reactions, with a smaller portion given on Day 1 and the remainder on Day 2. This initial infusion typically starts at a slower rate and is gradually increased, making it a longer session.
Subsequent infusions for obinutuzumab are usually given once every 28 days for six cycles, lasting approximately three to five hours. For eligible patients, a shorter 90-minute infusion may be possible from Cycle 2 onward if the initial infusion was well-tolerated. Following initial cycles, obinutuzumab may be continued as monotherapy for up to two years for certain conditions like follicular lymphoma.
Rituximab’s first infusion typically takes longer, often four to six hours or more, to monitor for potential reactions. Subsequent infusions usually take less time, generally three to four hours.
In some cases, for conditions like previously untreated follicular lymphoma, a rapid 90-minute infusion may be an option from the second treatment cycle if the first infusion was tolerated without serious reactions. Treatment schedules for rituximab vary by indication; for example, in CLL, it is often given in six 28-day cycles.
Pre-medications, including acetaminophen, an antihistamine, and often a corticosteroid, are given before each infusion of both drugs to help prevent or reduce infusion-related side effects.