On September 2, 2020 AbbVie (NYSE: ABBV ) reported the publication of the results of a three-year follow-up analysis of the CLL14 clinical study, which demonstrated that after a period of at least 24 months from the end of treatment, patients with chronic lymphocytic leukemia (CLL) without previous treatment, when submitted to a fixed duration treatment of VENCLEXTA (venetoclax) plus obinutuzumanbe, maintained higher rates of Disease Progression-Free Survival, when in comparison to the group of patients who received chlorambucil in combination with obinutuzumab (median not achieved vs. 35.6 months; Risk Rate [HR] = 0.31 [95 percent CI 0.22-.44]) 1 (Press release, AbbVie, SEP 2, 2020, View Source [SID1234564362]). SLP is the period between the start of treatment until the progression of the disease or death of the patient.
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The data set for this analysis was published in the September issue of the scientific journal The Lancet Oncology . 1
"AbbVie is committed to helping raise the standard of care for cancer patients, and while there is still a lot to be done, the results of the CLL14 study are promising for a difficult-to-treat patient population," said Marco Paschoalim, Director AbbVie doctor. "We are encouraged by the progress we have seen in treating blood cancers that are quite challenging, such as LLC. And AbbVie remains committed to expanding the discovery and development of new treatments to help more cancer patients."
In three years, with an average follow-up of approximately 40 months, the estimated progression-free survival rate was 81.9% in the study arm treated with venetoclax-obinutuzumab and 49.5% in the arm treated with chlorambucil-obinutuzumab. This result was consistent across all risk groups, clinical and biological, including patients with mutation / deletion of the TP53 gene and non-mutated IGHV1.
The analysis also noted that patients who received venetoclax-obinutuzumab maintained higher rates of undetectable DRM in peripheral blood, than patients who received chlorambucil-obinutuzumab, at 18 months after completion of treatment (47.2 percent vs. 7, 4 percent, respectively). The overall survival factors (SG) were similar in both groups, with the death of 27 patients (12.5%) in each arm of the study. Median SG was not achieved in any of the treatment groups. At the three-year follow-up mark, 88 percent and 88.9 percent, respectively, of the patients, the chlorambucil-obinutuzumab and venetoclax-obinutuzumab arms were alive. 1
The purpose of this analysis was to evaluate the effectiveness and durability of a first-line, fixed-term treatment for CLL with an emphasis on DRM in three years of follow-up, after the completion of 12 months of treatment with the combined venetoclax and obinutuzumab regimen. The observed safety profile of the combined therapeutic regimen was, in general, consistent with the known safety profiles of the two drugs alone.
"We have to establish a fixed-term treatment regimen, which achieves higher rates of minimal undetectable residual disease, for patients with previously untreated CLL, as they are generally elderly and have difficulty following a continuous chemotherapy program," said Dr. Othman. Al-Sawaf, Department of Internal Medicine, Center for Integrated Oncology Aachen, Bonn, Cologne, is a member of the German LLC Study Group and lead author of The Lancet Oncology article . "Given the advanced average age of patients in this study, a considerable fraction of patients treated with the venetoclax-obinutuzumab combination can be subjected to only this treatment regimen, allowing them to enjoy their daily activities."
The most frequent serious adverse reactions (> 2 percent) in patients who received venetoclax in combination with obinutuzumab or rituximab were pneumonia, sepsis, febrile neutropenia and SLT (tumor lysis syndrome). Common adverse reactions (> 20 percent) of any degree in patients who received venetoclax in the combined studies were neutropenia, diarrhea and upper respiratory tract infection .1
LLC is a slow-progressing cancer of the blood and bone marrow, in which some white blood cells, called B lymphocytes, become cancerous and multiply abnormally. LLC is the most common form of leukemia in the West, accounting for approximately one third of new leukemia cases 2,3. In Brazil, according to information from INCA 2018, there are 10,800 new cases of leukemia in the year.
About the CLL14 Study
The CLL14 Phase 3 study (prospective, randomized, multicenter, active, controlled), conducted in collaboration with the German LLC Study Group (DCLLSG), assessed the efficacy and safety of venetoclax and obinutuzumab (n = 216) , in comparison with obinutuzumab and chlorambucil (n = 216) in patients without previous treatment of the disease and with coexisting medical conditions. The therapies were administered over a fixed period of 12 cycles of venetoclax in combination with six cycles of obinutuzumab. The cycles comprised 28 days.
About VENCLEXTA (venetoclax)
VENCLEXTA (venetoclax) first in a new class of drugs that selectively inhibits the Bcl-2 protein. In some types of blood cancer and other tumors, BCL-2 prevents the natural process of cancer cell death, or a process of self-destruction called apoptosis. VENCLEXTA targets this protein, BCL-2, and acts to restore the apoptosis process. Venetoclax has been developed by AbbVie and Roche. It is marketed jointly by AbbVie and Genentech, a member of the Roche Group , in the USA; and AbbVie outside the US.