Dr. Smith on Frontline Treatment Considerations in CLL

Mitchell R. Smith, MD, PhD, division director, Cancer & Blood Disorders, and professor of medicine, GW Cancer Center, discusses frontline treatment considerations in patients with chronic lymphocytic leukemia (CLL).

Fludarabine/cyclophosphamide/rituximab (Rituxan; FCR), bendamustine/rituximab, and ibrutinib (Imbruvica) monotherapy are all indicated for use in patients with newly diagnosed CLL. Therefore, the treatment decision has to be made on an individualized basis. For example, young, fit patients with IGHV mutations may do better on FCR than on ibrutinib, says Smith. Data have shown that this subpopulation of patients can reach 10 years without progression after 6 months of FCR.

Considering cost, adverse events, and toxicity, BR could also be used as frontline therapy. If after several years, patients relapse, they can turn to ibrutinib—either alone or in combination. There is no known optimal therapy because there are no head-to-head data, says Smith.

However, a lot of work is being done on resistant clones and ways to detect them early, which could potentially inform subsequent treatment decisions. The goal is to be able to personalize these treatments and come up with the best strategy for each patient, says Smith. In the future, that could include following patients and monitoring their blood to see if the clones have the mutation that makes PI3K upregulate and makes BTK resistant to ibrutinib. These are all strategies that are on the horizon, concludes Smith.