GAZYVA

What it is

Gazyva contains obinutuzumab . Each vial of 40 mL concentrate contains 1000 mg obinutuzumab, corresponding to a concentration before dilution of 25 mg/mL . It is presented as a clear, colourless to slightly brownish concentrate for solution for infusion .

Approved indications

— Treatment of patients with previously untreated chronic lymphocytic leukaemia in combination with chlorambucil . — Treatment of patients with previously untreated advanced follicular lymphoma in combination with chemotherapy followed by Gazyva maintenance . — Treatment of patients with follicular lymphoma who did not respond to, or who progressed during or up to 6 months after treatment with rituximab or a rituximab-containing regimen, in combination with bendamustine followed by Gazyva maintenance . — Pre-treatment to reduce the risk of cytokine release syndrome induced by glofitamab .

Dosing overview

For chronic lymphocytic leukaemia, the recommended dosage is 1000 mg administered over Day 1 and 2, and on Day 8 and Day 15 of the first 28-day treatment cycle, given as two infusions of 100 mg and 900 mg. If the 100 mg dose is completed without modifications or interruptions, the 900 mg dose can be administered on the same day; otherwise it must be given the following day. For cycles 2–6, the recommended dosage is 1000 mg administered on Day 1 for each 28-day treatment cycle . For follicular lymphoma, the recommended dosage is 1000 mg administered intravenously. Previously untreated patients should receive six 28-day cycles in combination with bendamustine, or six 21-day cycles in combination with CHOP, followed by 2 additional cycles of Gazyva alone, or eight 21-day cycles in combination with CVP . Previously untreated patients who achieve a complete or partial response should continue to receive Gazyva 1000 mg alone as maintenance therapy once every 2 months until disease progression or for up to 2 years . For relapsed or refractory follicular lymphoma, Gazyva should be administered in six 28-day cycles in combination with bendamustine . Relapsed or refractory patients who achieve complete or partial response or have stable disease should continue to receive Gazyva 1000 mg alone as maintenance therapy once every 2 months until disease progression or for up to 2 years . As a pre-treatment to reduce the risk of cytokine release syndrome induced by glofitamab, the recommended dose is a single 1000 mg dose of Gazyva administered intravenously 7 days prior to initiation of glofitamab .

Key safety warnings

Progressive Multifocal Leukoencephalopathy including fatal cases can occur in patients receiving Gazyva. Patients must be monitored for any new or worsening neurological symptoms or signs suggestive of PML. If such symptoms occur, further administration of Gazyva should be immediately suspended until a diagnosis of PML has been excluded. If a diagnosis of PML is confirmed, Gazyva must be permanently discontinued . Infusion-related reactions are the most frequently observed adverse drug reactions and occur predominantly during infusion of the first 1000 mg. In patients who received combined prevention measures including corticosteroid premedication, oral analgesic, antihistamine, and omission of antihypertensive medication, a decreased incidence of infusion-related reactions of all grades was observed . In the majority of patients, infusion-related reactions were mild to moderate and could be managed by slowing or temporarily halting the first infusion, but severe and life-threatening reactions requiring symptomatic treatment have also been reported . Tumour lysis syndrome has been reported with Gazyva. Patients considered to be at risk, such as those with high tumour burden and/or high circulating lymphocyte count (greater than 25 × 10⁹/L) and/or renal impairment (creatinine clearance less than 70 mL/min), should receive prophylaxis consisting of adequate hydration and administration of uricostatics such as allopurinol, or a urate oxidase such as rasburicase, prior to infusion of Gazyva . Severe and life-threatening neutropenia including febrile neutropenia has been reported during treatment with Gazyva. Patients who experience neutropenia should be closely monitored with regular laboratory tests until resolution. Concomitant infection should be treated as appropriate, and dose delays should be considered in case of severe or life-threatening neutropenia . Severe and life-threatening thrombocytopenia including acute thrombocytopenia occurring within 24 hours after infusion has been observed during treatment with Gazyva. Fatal haemorrhagic events have also been reported in Cycle 1. Patients should be closely monitored for thrombocytopenia, especially during the first cycle, with regular laboratory tests until the event resolves and dose delays considered in case of severe or life-threatening thrombocytopenia . Gazyva should not be administered in the presence of an active infection and caution should be exercised when considering its use in patients with a history of recurring or chronic infections. Serious bacterial, fungal, and new or reactivated viral infections can occur during and following completion of Gazyva therapy. Fatal infections have been reported . Hepatitis B virus reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with Gazyva. Screen all patients for hepatitis B infection by measuring hepatitis B surface antigen and hepatitis B core antibody before initiating treatment. For patients who show evidence of hepatitis B infection, consult physicians with expertise in managing hepatitis B regarding monitoring and consideration for antiviral therapy. Monitor patients with evidence of current or prior hepatitis B infection for clinical and laboratory signs of hepatitis or reactivation during and for at least 12 months following treatment with Gazyva .

Contraindications

Gazyva is contraindicated in patients with a known hypersensitivity to obinutuzumab, murine proteins or to any of the excipients .

PBS listing

The solution for intravenous infusion 1000 mg in 40 mL has 16 PBS items with streamlined and authority-required restrictions, with an ex-manufacturer price of A$4299.24 .

Regulatory history

Gazyva was first listed on the ARTG on 2014-05-15 . In April 2018, the PBAC recommended extending PBS listing for previously untreated advanced follicular lymphoma and rituximab-refractory follicular lymphoma, and also recommended extending bendamustine listing for rituximab-refractory follicular lymphoma in combination with obinutuzumab . In July 2018, the PBAC recommended changing the chronic lymphocytic leukaemia listing from Authority Required (Written) to Authority Required (STREAMLINED), based on lower than predicted utilisation and recent listings of other drugs for chronic lymphocytic leukaemia . On 2023-05-03, the TGA approved an extension of indication for Gazyva as a pre-treatment to reduce the risk of glofitamab-induced cytokine release syndrome .