Each year over eighteen thousand people in the United States are diagnosed with diffuse large B-cell lymphoma (DLBCL) a common type of non-Hodgkin lymphoma.
A recent FDA news release announced its accelerated approval of Polivy (polatuzumab vedotin-piiq) in combination with Bendamustine and Rituxan (BR) to treat adult DLBCL patients. The drugs have been developed to treat cases where the disease has progressed and also when the patient has relapsed after receiving two previous therapies.
Accelerated approval allows the FDA to acknowledge drugs designed to treat serious conditions that do not currently have appropriate treatment. The drugs must also have the potential of clinically benefiting patients. Additional clinical trials must be conducted to verify that benefit.
A New Class of Drugs
Polivy is one of the antibody-drug conjugates (ADCs) that are classified as targeting immunotherapies to treat cancer. ADCs are a new class of drugs that have gained attention from pharmaceutical companies. Unlike traditional chemotherapy, ADCs target specific cells. The ADCs consist of a cytotoxic drug, an mAb and a linker.
- Cytotoxic drugs eradicate cancers cells
- An mAb is an antibody (fights foreign substances; e.g. antigens)
- A linker connects the cytotoxic drug to the antibody
Polivy binds to a protein called (CD79b) found on B cells. The cytotoxic drug is then released into the B cells.
About Bendamustine Hydrochloride
Bendamustine was granted approval to treat slow-growing B-cell non-Hodgkin lymphoma that had worsened when treated with single agent rituximab or during the six month period following treatment.
Rituxan, a Monoclonal Antibody
Antibodies are grouped according to their function and structure.
Rituxan is classified as a monoclonal antibody (mAb). This is a type of immunotherapy that utilizes man-made antibodies in their attack on cancer.
Note that Bendamustine and Rituxan combined are referred to as “BR”.
About the CD20 Antigen
Some non-Hodgkin lymphoma cells carry markers that distinguish them from other cells. The CD20 antigen is such a marker. It adheres to certain immune cells called B-lymphocytes or B cells, a form of white blood cells. The B cells can become cancerous in certain types of non-Hodgkin lymphoma.
Rituxan recognizes the surface markers and as an “artificial antibody” it adheres to the C20 antigen on the cancerous B cells. Its mechanisms are activated and the cancer cells are destroyed.
High Rate of Relapse
Non-Hodgkin Lymphoma can be cured. However, about thirty to forty percent of patients relapse. This fast-growing cancer is found in the bone marrow, lymph nodes, liver, spleen, and other organs. Symptoms include weight loss, fever, and swollen lymph nodes.
The side effects of Polivy combined with BR are common to many drugs. Patients most often experience low levels of white blood cells, platelets, and red blood cells. Other side effects include nerve damage, fatigue, diarrhea, fever, pneumonia, and loss of appetite.
Eighty Evaluable Patients
Eighty patients with DLBCL who had either relapsed or whose disease was resistant to treatment (refractory) were included in a study to determine the efficacy of the drugs.
The patients randomly received either Polivy with BR or BR as a single agent. Efficacy was determined by a patient’s complete response and the time that the disease remained in remission.
The end results of the trial were favorable. Forty percent of patients treated with Polivy plus BR showed a complete rate of response. This compares to eighteen percent treated with BR.
Sixteen, or sixty-four percent of the patients who received a response to Polivy combined with BR remained in remission for a minimum of six months. Twelve patients, or forty-eight percent, were reported to have remained in remission for at least twelve months.
Advice from the FDA
Patients must be monitored closely for reactions related to infusions, low blood counts and severe infections. One severe reaction is called tumor lysis syndrome (TLS). The number of TLS occurrences has fallen dramatically as a result of diligent monitoring. However, the threat still exists and physicians are warned to be on the alert.
TLS is treatment-related and can be fatal. It occurs when uric acid and other substances are released as a result of the breakdown of tumor cells. Kidney failure may occur as a result of the buildup of uric acid.
Other adverse events include liver damage and multifocal leukoencephalopathy, an infection of the brain. Women should not take Polivy during pregnancy as it may harm the fetus.
Polivy has been granted the following designations for drugs that are being developed to treat serious diseases:
- Breakthrough Therapy designation that expedites development and review of drugs
- Priority Review designation whereby the FDA intends to take action within six months
- Orphan Drug designation that gives incentives to encourage the development of drugs for rare diseases
- Accelerated Approval that uses a surrogate endpoint as a measure to predict clinical benefit
The above-noted FDA approvals of Polivy were granted to Genentech.