Gazyva (obinutuzumab) for Follicular Lymphoma

Team discussing test results and next steps.

Gazyva (Obinutuzumab) is a medicine that is similar to Rituxan (rituximab) and is being investigated across various types of blood cancers, including multiple clinical studies in non-Hodgkin’s lymphoma (NHL). Like Rituxan, Gazyva is used in combination with chemotherapy for the treatment of certain blood cancers. Drugmakers Genentech and Roche note that there are multiple ongoing studies comparing obinutuzumab with rituximab in indolent non-Hodgkin's lymphoma and for diffuse large B-cell lymphoma.

Gazyva is now FDA-approved for use in certain patients with follicular lymphoma, in addition to it's established use in chronic lymphocytic leukemia, or CLL. For CLL, Gazyva is combined with chlorambucil; for follicular lymphoma, Gazyva is combined with bendamustine.

About Follicular Lymphoma

Though not the most common lymphoma, follicular lymphoma does rank among the most commonly diagnosed lymphoma types. The two basic categories of lymphoma are Hodgkin’s and non-Hodgkin’s lymphoma. Follicular lymphoma is a non-Hodgkin's type and is the most common of the indolent, or slow-growing, non-Hodgkin’s lymphomas (NHL).

Although it's slow growing, it remains incurable cancer that becomes more difficult to treat each time it comes back. Follicular lymphoma accounts for about one in five cases of NHL in the United States, where it was estimated that more than 14,000 new cases would be diagnosed in 2015. As more patients successfully keep the malignancy at bay, new treatments are especially welcome.

Gazyva for Follicular Lymphoma

“People with follicular lymphoma whose disease returns or worsens despite treatment with a Rituxan-containing regimen need more options because the disease becomes more difficult to treat each time it comes back,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Gazyva plus bendamustine provides a new treatment option that can be used after relapse to significantly reduce the risk of progression or death.”

The FDA approval of Gazyva was based on results from the Phase III GADOLIN study, which showed that, in people with follicular lymphoma whose disease progressed during or within six months of prior Rituxan-based therapy, Gazyva plus bendamustine followed by Gazyva alone demonstrated a 52 percent reduction in the risk of disease worsening or death (progression-free survival, PFS), compared to bendamustine alone.

How Gazyva Works

Gazyva, like Rituxan, is a monoclonal antibody. That is, it's a special kind of antibody engineered by scientists and produced by manufacturers. The final product is hung in a bag as a liquid and given via intravenous infusion.

Like Rituxan, Gazyva targets the CD20 antigen. The CD20 antigen is like an identifying tag -- it's a protein complex that is present on the surface of certain cells, including the white blood cells known as B-lymphocytes, or B cells. Immature B cells, called pre-B cells, also have this CD20 antigen.

When obinutuzumab binds to CD20, this leads to the death and spilling open of B cells. It does so by recruiting other immune cells to do the job, by directly activating death signals and/or activating something called the complement cascade – a series of chemical reactions your immune system uses, signaling the need to seek and destroy.

How does Gazyva differ from Rituxan? Well, according to the drug makers, Gazyva is thought to have an increased ability to induce direct cell death -- something called antibody-dependent cellular cytotoxicity (ADCC) -- and it induces greater activity in how it recruits the body’s immune system to attack B-cells when compared to rituximab. In fact, in preclinical studies, Gazyva delivered up to a 35-fold increase in ADCC compared to Rituxan. Gazyva also activated death signals within the B cells in preclinical studies.

Side Effects

The safety of Gazyva was evaluated based on 392 patients with indolent NHL, of whom 81 percent had follicular lymphoma. In patients with follicular lymphoma, the most common side effects that were seen were consistent with the overall population who had indolent NHL.

The most common side effects of Gazyva are infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness, and urinary tract infection.

Rare but life-threatening side effects are reported in doctors' prescribing information, sometimes taking the form of a "boxed warning." For Gazyva, this boxed warning includes information about two viral infections: Hepatitis B Virus (HBV) reactivation in some cases resulting in severe liver damage and death; and JC virus infection Progressive Multifocal Leukoencephalopathy (PML) resulting in death.

For the complete safety and efficacy profile of Gazyva in follicular lymphoma, please see the Gazyva Prescribing Information.

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Article Sources
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