Front-line Combinations with New Agents Evolve Chronic Lymphocytic Leukemia Landscape

While novel agents continue to evolve in the treatment landscape for chronic lymphocytic leukemia (CLL), many may start to be combined in the front-line setting as well, according to Matthew S. Davids, M.D., MMSc.

“The field is going to continue to evolve very quickly over the next several years,” he added in an interview with CURE’s sister publication, OncLive. “We're going to continue to have more and more treatment options for our patients.”

Historically, chemoimmunotherapy-based regimens have served as the first line therapy for newly diagnosed patients, especially in younger, lower-risk patients with IGHV-mutated disease, explained Davids, who is associate director of the CLL Center at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School. In addition, newer drugs such as Imbruvica (ibrutinib) and Venclexta (venetoclax) have also become an option in the front-line setting.

Davids added that the use of FISH testing or next-generation sequencing panels, which account for important markers such as TP53, 17p deletion, and IGHV, can help clarify whether a patient is best suited for a novel combination or standard chemoimmunotherapy.

“First, we tend to think about whether patients have 17p deletion or not. If they have this high-risk marker, then we gravitate toward an ibrutinib- or novel agent-based strategy,” he explained. “If they have lower-risk disease, particularly if they have the mutated IGHV gene, then we tend to think more about chemoimmunotherapy. Particularly for younger patients, fludarabine, cyclophosphamide and Rituxan (rituximab; FCR) may have curative potential. Then you have a middle group of patients in whom you can consider chemoimmunotherapy. However, we’re increasingly using a (Venclexta)- or (Imbruvica)-based strategy for those patients.”

Meanwhile, novel regimens have been evaluated such as the combination use of Venclexta and Gazyva (obinutuzumab) in patients with treatment-naïve CLL who have coexisting medical conditions. In a phase 3 study, topline findings have demonstrated the experimental combination significantly reduced the risk of disease progression or death compared with a chemoimmunotherapy regimen.

“Soon, we're going to see data from the (Venclexta)/(Gazyva) trial, CLL14, and those results will lead to a new standard of care for frontline CLL treatment,” said Davids. "We'll also see data maturing on the (Imbruvica)/(Venclexta) combinations. Many of those are going into phase 3 trials now. Those studies could potentially change the standard of care.”

This article was adapted from an article that originally appeared on OncLive, titled “Novel Regimens Take Precedence in Newly Diagnosed CLL.”