Susan M. O’Brien, MD, hematologist/oncologist at University of California, Irvine Health, discusses combination venetoclax (Venclexta) in the treatment of patients with chronic lymphocytic leukemia (CLL).

In June 2018, the FDA granted a full approval of venetoclax for the treatment of patients with CLL regardless of 17p deletion, and following at least 1 prior therapy. The BCL-2 inhibitor is now also approved for use in combination with rituximab (Rituxan) in the same patient population.

The approval of the combination was based off the phase III MURANO trial, which showed that median follow-up was not reached with venetoclax plus rituximab compared with 18.1 months (95% CI, 15.8-22.3) with bendamustine plus rituximab (HR, 0.19; 95% CI, 0.13-0.28; 

<.0001). Overall response rate for venetoclax plus rituximab was 92% compared with 72% for bendamustine plus rituximab.

O’Brien says that now clinicians have the option of treating their patients with single-agent venetoclax, or the combination of venetoclax plus rituximab for 2 years.

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Susan M. O’Brien, MD, hematologist/oncologist at University of California, Irvine Health, discusses combination venetoclax (Venclexta) in the treatment of patients with chronic lymphocytic leukemia.

Dr. O'Brien Discusses Combination Venetoclax in CLL

Susan M. O’Brien, MD, hematologist/oncologist at University of California, Irvine Health, discusses sequencing small molecule inhibitors in chronic lymphocytic leukemia (CLL).

Ibrutinib (Imbruvica) is currently the only small molecule inhibitor with a frontline label, so that tends to be the preferred frontline agent. Although, there is a role for chemotherapy, explains O’Brien. Many physicians will use duvelisib and fludarabine-cyclophosphamide-rituximab (FCR) who have a mutated 

 gene, as many studies have shown a plateau on the progression-free survival curve in patients with a mutation in 

. However, where physicians do not want to use FCR, ibrutinib will be used, says O’Brien. This decision is often based on mutation status as well as 17p deletion status, as chemotherapy is ineffective in patients with 17p deletion.

If the patient is intolerant to ibrutinib, idelalisib (Zydelig) plus rituximab (Rituxan) or venetoclax (Venclexta) can easily be adopted, explains O’Brien. However, patients who are refractory to ibrutinib may not experience lasting response with idelalisib. Whereas, venetoclax in the setting of ibrutinib resistance can induce durable responses alongside minimal residual disease negativity, says O’Brien.

Susan M. O'Brien

Articles

Dr. O'Brien Discusses Combination Venetoclax in CLL

Dr. O'Brien on Sequencing Small Molecule Inhibitors in CLL