Research Offers Insight into Evolving Clinical Practice

SAN ANTONIO—The massive VA health database revealed unique insights into the treatment of chronic lymphocytic leukemia in actual clinical practice to a team of researchers based at the South Texas Veterans Health Care System in San Antonio. It also revealed significant differences between the use of the drugs and modifications needed in typical CLL patients compared to those in the clinical trials for novel agents approved for this form of leukemia.

The findings of their research, the largest real world study conducted on CLL, were presented at the 61st American Society of Hematology Annual Meeting in December by Zohra Nooruddin, MD, a staff hematologist at the VA.

CLL is the most common type of leukemia, affecting about 20,000 individuals in the U.S. each year. The disease typically affects the elderly, with an average age at diagnosis of 70 years. Men have a somewhat greater risk of developing CLL than women.

Since 1993, nearly 27,000 veterans have received care for CLL through the VA. Because veterans treated by the VA tend to be older and male, they already have two risk factors for the disease. In addition, CLL is considered a presumptive condition for veterans exposed to Agent Orange or certain other herbicides during the Vietnam War.

CLL may progress very slowly and patients with this indolent form can often go years with just watchful waiting to monitor the disease. Patients who have higher levels of two proteins, ZAP-70 and CD38, tend to have a more aggressive form of CLL that will require active treatment to keep it at bay, according to the American Cancer Society.

New targeted therapies and immunotherapy agents have received approval from the U.S. Food and Drug Administration over the last decade, rapidly expanding the options for treatment as they joined chemotherapy, radiation therapy, and watchful waiting, which had been the previous alternatives.

Ofatumumab and obinutuzumab gained approval as monoclonal antibodies that target CD20, a protein on the surface of B lymphocytes. Like rituximab, the first in this class, they are typically used with chemotherapy or a targeted drug to treat CLL. Ibrutinib, acalabrutinib, idelalisib and duvelisib are all kinase inhibitors that act on either Bruton’s tyrosine kinase or the P13K protein. Venetoclax targets BCL-2, a protein that extends the life span of CLL cells.

“Usage of novel agents has increased drastically since they were first approved in 2014,” Nooruddin told U.S. Medicine. “The number of patients treated with the drugs doubled in recent years and continues to increase, consistent with national practices and society guidelines. As indications are changing, novel agents are being used more upfront and VA is adopting those practices.”

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