obinutuzumab

Instructions for Obinutuzumab

Common name: Obinutuzumab
Trade name: Gazyva
All names: Obinutuzumab, Obinutuzumab, Gazyva

Indications:
GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody indicated:
(1) In combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia.
(2) GAZYVA monotherapy in combination with bendamustine for the treatment of patients with follicular lymphoma who have relapsed or been refractory to rituximab.
(3) In combination with chemotherapy followed by GAZYVA monotherapy to achieve at least partial response, for the treatment of adult patients with previously untreated stage II bulky, III or IV follicular lymphoma.

Usage and dosage:
(1) Dilute and administer as intravenous infusion. Do not give as an intravenous push or bolus injection.
(2) Chronic lymphocytic leukemia dose: 100mg on day 1, 900mg on day 2 of cycle 1, 1000mg on days 8 and 15 of cycle 1, and 1000mg on day 1 of weeks 2-6.
(3) Follicular lymphoma dose: 1000 mg on days 1, 8 and 15 of cycle 1, 1000 mg on day 1 of cycles 2-6 or weeks 2-8, then 1000 mg every 2 months for up to 2 years.

Adverse reactions:
The most common adverse reactions (incidence ≥10%): infusion reactions, neutropenia, thrombocytopenia, anemia, fever, cough, musculoskeletal disorders.

Contraindications:
GAZYVA is contraindicated in patients with known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or any excipient, including serum reactions to prior use of obinutuzumab.

Notes:
Infusion reactions: Patient was premedicated with corticosteroids, acetaminophen, and antihistamines. Monitor closely during the infusion and interrupt or terminate the infusion for reactions.
Tumor Lysis Syndrome: Expect tumor lysis syndrome; premedicate with antihyperuricemic agents and adequately hydrate especially in patients with high tumor burden and/or high circulating lymphocyte count. Correct electrolyte abnormalities, provide supportive care, and monitor renal function and fluid balance.
Neutropenia: Surveillance for infection.
Thrombocytopenia: Monitor blood counts and bleeding. Management of bleeding may require blood product support.
Immunizations: Do not give live virus vaccine before or during administration of GAZYVA.

Storage:
Stable at 2°C to 8°C (36°F to 46°F). Do not use beyond the expiry date marked on the carton. GAZYVA vials should be protected from light. Do not freeze. Don't shake.

Mechanism of action:
Obinutuzumab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B lymphocytes. Upon binding to CD20, obinutuzumab mediates B cell lysis through (1) binding of immune effector cells, (2) through direct activation of intracellular death signaling pathways (direct cell death), and/or (3) activation of the complement cascade. Immune effector cell mechanisms include antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis. As an antibody with reduced fucose content, obinutuzumab induces higher ADCC activity in vitro using human cancer cell lines. Obinutuzumab also showed increased potency to induce direct cell death compared to rituximab. Obinutuzumab binds to FcγRIII using a purified protein with higher affinity than rituximab. Obinutuzumab and rituximab bind with similar affinity to overlapping epitopes on CD20.

Safety and efficacy:
In November 2013, Gazyva (obinutuzumab), the second-generation anti-CD20 monoclonal antibody developed by Genentech, was approved by the FDA in combination with chlorambucil for the treatment of chronic lymphocytic leukemia. The survival period is better than that of the first-generation rituximab.
In CLL-11, GAZYVA demonstrated superior PFS (progression-free survival) to the rituximab product in combination with first-line drugs for the treatment of first-line patients. Through the planned 6 courses, GAZYVA (obinutuzumab) significantly improved the median PFS (26.7 months vs. 14.9 months) compared with the rituximab product in first-line CLL.
GAZYVA + Clb reduced the risk of CLL progression or death by 58% compared with rituximab + Clb (HR = 0.42; 95% CI; 0.33-0.54; P < 0.0001). GAZYVA has a higher response rate compared to rituximab products.