Jose Leis, MD
Standard treatment approaches for patients with chronic lymphocytic leukemia (CLL) will continue to include fludarabine, cyclophosphamide, and rituximab (FCR) and allogeneic stem cell transplantation.
In an interview, Leis, a professor of Medicine and head of the Chronic Lymphocytic Leukemia Program at Mayo Clinic, spoke on the current state of the disease and pivotal clinical trial findings in CLL to be presented at the 2016 ASH Annual Meeting. Additionally, he provided insight into the potential of chimeric antigen receptor (CAR) T-cell therapies in CLL and how the treatment paradigm will look in the coming years.
OncLive: How have we seen the field of CLL evolve?
: The world of CLL therapy has just really dramatically changed in the last 20 years. I got interested in CLL because my father-in-law called while I was a young faculty member at Harvard and told me he had been diagnosed with CLL. In 1995, we didn’t know about prognostic factors; we didn’t really know anything about the clinical course of aggressive CLL. Unfortunately, within 3 years, he passed from his disease.
The second thing that really happened in the late 2000s was the understanding that the B-cell–receptor pathway plays a major role. Once that became known, then targeted therapies could be developed. We went from chlorambucil as single therapy, lymphoma-type regimens with fludarabine and purine analogs, and then combination therapy. In the 2010s, the era has become that of targeted therapies.
What is the state of the disease now?
It is depending on each individual patient. The University of Texas MD Anderson Cancer Center group and the Germans who collaborated on this mutational status study are playing a major role. Twenty percent to 40% and more of patients treated with FCR who had the mutated subtype immunoglobulin genes had favorable cytogenetics. At a 13-year follow-up, they don’t have any evidence of disease.
Therefore, MRD status is playing a role here. However, the important thing is that, potentially, chemoimmunotherapy can cure some patients. That is really very different than we used to think—that nobody could be cured. For favorable-risk patients who are young and fit, FCR may cure a subset of those patients.
For the high-risk patients, you need targeted therapies, which have been nothing but phenomenal. The response rates seen with single agents have been at more than 80%. Results with ibrutinib have been dramatic in the high-risk 17p deletion patients. It looks like upfront therapy with ibrutinib is better than in the relapsed/refractory setting; we know that patients with 17p deletion who have had other therapies will relapse at a median of 28 months. However, that has been much better with upfront therapy.
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