Imbruvica-Venclexta Combination Demonstrates Benefits in Untreated CLL

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Results from a four-year follow-up of a phase 3 trial determined that the combination of Imbruvica and Venclexta provided benefits for untreated patients with CLL.

The treatment combination of Imbruvica (ibrutinib) and Venclexta (venetoclax) has demonstrated beneficial results regarding progression-free survival (PFS; length of time during and after treatment when a patient lives with disease, but it does not worsen) when compared with the chemotherapy chlorambucil plus the immunotherapy Gazyva (obinutuzumab) in previously untreated patients with chronic lymphocytic leukemia (CLL), according to a study.

Imbruvica is a type of targeted therapy in the form of an oral pill that is commonly used to treat patients with CLL. This drug blocks a protein called BTK, which can help prevent the growth of cancer cells, according to the National Cancer Institute.

Venclexta is another targeted therapy in the form of an oral pill that is used to treat people with CLL. This drug binds to a protein called BCL2, which makes it more vulnerable to anti-cancer cells and helps destroy the cancer cells, as defined by National Cancer Institute.

A study from The Lancet Oncology included 211 patients in a four-year follow-up of the phase 3 GLOW trial. Patients were randomly assigned across two groups: the Imbruvica-Venclexta combination group or the chlorambucil-Gazyva combination group. There were 106 patients in the Imbruvica-Venclexta group and 105 patients in the chlorambucil-Gazyva group.

“Both (chlorambucil and Gazyva are) pretty well-tolerated agents before the targeted therapy. So, this is why (the researchers from the GLOW trial) chose this as a control arm, and in general, they are pretty well-tolerated,” said Dr. Jing-Zhou Hou, a clinical hematological oncologist for Mario Lemieux Center for Blood Cancers at UPMC Hillman Cancer Center, said during an interview with CURE®.

“However, chlorambucil is chemotherapy,” Hou added. “When we give people chemotherapy, we always worry about short-term toxicity, as well as long-term toxicities, such as a secondary malignancy, including leukemia or MDS (myelodysplastic syndromes), and also, the combination is a historical control.”

The study from The Lancet Oncology aimed to evaluate how beneficial fixed-duration treatment would be for patients with CLL who were not previously treated, demonstrating positive results.

“I think this is the beauty of this trial, you can (have) fixed duration with two powerful drugs and after one year (of) therapy, you can stop the treatment,” said Hou. “After you stop the treatment, you monitor the patient, just in case a number of years later, if the disease comes back and you need to treat again … the drug will still work for this patient.”

Treatments that are fixed duration, Hou noted, are “a relief” for patients, as they don’t need to be continuously treated.

The researchers from the study established that at 46 months of follow-up, the progression-free survival for the Imbruvica-Venclexta group was superior to the chlorambucil-Gazyva group.

According to the study, the 42-month PFS for the Imbruvica-Venclexta group was 74.6%, whereas the PFS for the chlorambucil-Gazyva group was 24.8%, which Hou noted was “quite impressive for these new agents.”

There were 15 deaths in the Imbruvica-Venclexta group, in which one death was from disease progression and seven other patients died from treatment-emergent side effects. Of these seven deaths from treatment-related side effects, six occurred during remission and one occurred during subsequent therapy. The researchers also found that four deaths were caused by infection, including COVID-19.

In the chlorambucil-Gazyva group, the study researchers reported 30 total deaths. Two deaths were from treatment-emergent side effects including one, from pneumonia, that was determined to be treatment-related. Of the remaining 27 deaths in this group, six occurred during remission, 13 occurred after their disease progressed and eight occurred while receiving subsequent therapy.

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