Jose Leis, MD, associate professor of Medicine, Mayo Clinic, discusses combination regimens that seem promising and are under investigation in the treatment landscape of chronic lymphocytic leukemia (CLL).

Targeting different pathways simultaneously will definitely increase the potential for responses, explains Leis. However, researchers should be cautious and continue to do clinical trials, as researchers are not always able to accurately predict the results, he says. However, targeting BCL-2—which is overexpressed in almost all patients with CLL&mdash;while targeting other pathways will likely lead to very intriguing results. Such a combination being explored is venetoclax (Venclexta) plus ibrutinib (Imbruvica).

These data are not yet mature, but Leis says that early findings are showing encouraging response rates. In the trial of venetoclax plus ibrutinib, Leis admits he would have predicted a higher response rate of the 2 drugs. Though there is great promise, he adds that venetoclax is an exciting therapy that, in combination, will improve over time.

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Jose Leis, MD, associate professor of Medicine, Mayo Clinic, discusses combination regimens that seem promising and are under investigation in the treatment landscape of chronic lymphocytic leukemia.

Dr. Leis on Promising Combo Regimens Being Explored in CLL

Jose Leis, MD, associate professor of Medicine, Mayo Clinic, discusses treatment-related advances in the field of chronic lymphocytic leukemia (CLL) over the last several decades in an interview during the 2016 

 State of the Science Summit on Hematologic Malignancies.

The biggest advances in the field started with the regimen of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), which was developed by Michael Keating at The University of Texas MD Anderson Cancer Center in the early 2000s. This combination regimen led to improved remission rates and responses in patients with CLL, Leis explains.

Secondly, there was an understanding developed that the B-cell receptor pathway plays a major role in treatment of the disease. Once this was realized, then researchers were able to develop therapies to target that receptor and pathway.

In the 1970s, practitioners used single-agent therapy with chlorambucil, as well as lymphoma-type regimens of fludarabine and purine analogues, followed by combination therapy in the 1980s. The last decade, he adds, has been primarily focused on targeted agents, which included ibrutinib (Imbruvica), idelalisib (Zydelig), and venetoclax (Venclexta).

The current status of disease depends on every individual patient and understanding their specific disease. Mutational status also is a major factor in the disease, Leis explains. Twenty to 40% of patients treated with FCR and had a mutated subtype of immunoglobulin genes and favorable cytogenetics are still without evidence of disease at 13-year follow-up.

Additionally, minimal-residual disease status is also important. However, it is important to note that chemoimmunotherapy can potentially cure some patients.

Jose Leis, MD, associate professor of Medicine, Mayo Clinic, discusses treatment-related advances in the field of chronic lymphocytic leukemia (CLL) over the last several decades in an interview during the 2016 OncLive State of the Science Summit on Hematologic Malignancies.

Jose Leis, MD

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