Early in the 1990s, anti-CD20 antibody therapy marked a significant improvement in the outcomes for patients with B-cell cancers. B-cell lymphoma is a type of cancer that originates in white blood cells known as lymphocytes.
However, the development of disease resistance, subsequent relapses, and a decline in the efficacy of ongoing therapies have led to the immune system mounting a response against CD20. This has paved the way for the exploration of alternatives to anti-CD20-related treatments.
CD20-Based Antibody Therapies
The National Cancer Institute identifies the CD20 antigen as a protein found on B-cells. An antigen is any substance that triggers the immune system to produce antibodies, whether in response to a real or perceived threat.
About Hairy-Cell Leukemia (HCL)
As recently reported in MedPage Today, HCL is characterized as a slow-acting (indolent) B-cell cancer, with the BRAF V600E mutation being one of the most common subtypes. The term “V600” describes the nature of the mutation, and the letters “V” and “E” specify the building blocks of the protein.
The combination of the BRAF inhibitor vemurafenib (Zelboraf) and Obinutuzumab (Gazyva) has shown high rates of complete remission (CR) when used to treat HCL patients in a small Phase II trial.
Of the two types of lymphocytes, the B-cells are the ones influencing the development of the disorder. B-cells are responsible for producing antibodies that aid in combating pathogens like viruses and bacteria.
Lymphocytes travel through the body and collect in various glands, including those in the groin, armpits, and neck. Lymphoma tends to develop in areas with abundant lymph tissue, including the thymus, stomach, adenoids, spleen, and bone marrow.
B-cell lymphoma arises when the body produces an excess of abnormal B cells that are ineffective in fighting infections. There are two main types of lymphoma, with non-Hodgkin’s lymphoma being the most common. The exact cause of B-cell lymphoma remains unknown.
In a healthy body, new lymphocytes are produced as needed. However, in individuals with B-cell lymphoma, lymphocytes accumulate unchecked.
About the Study
The study enrolled thirty evaluable patients, of whom twenty-seven achieved complete remission. Dr. Jae Park at New York’s MSK Cancer Center noted that three patients discontinued their treatment shortly after the study began due to adverse events that were reportedly unrelated to the treatment.
Expert Consensus
Obinutuzumab is a biopharmaceutical product obtained from biological sources, unlike completely synthesized pharmaceuticals such as whole blood or vaccines. It targets both normal and cancerous B-cells for destruction.
The combination of the BRAF inhibitor Zelboraf (vemurafenib) with Gazyva (Obinutuzumab) resulted in complete remission for twenty-seven evaluable patients with hairy cell leukemia, as reported in NEJM. Moreover, twenty-six participants achieved MRD negativity, which is considered the lowest detectable level of HCL cells.
Follow-up assessments were conducted at 34.9 months from the first vemurafenib dose and again at 36 months. At both time points, the progression-free survival rate was estimated at 97%. All participants were alive and without relapse as the study was published.
Conclusion
Dr. Park suggested that the data supports further investigation of Obinutuzumab plus vemurafenib. He also emphasized that while purine analogs have been in use for over twenty years and have achieved significant rates of complete remission, the disorder remains incurable, and the majority of patients will eventually experience relapses.
