Expert Point of View: Kostas Stamatopoulos, MD, PhD

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In the phase III GLOW trial, the all-oral regimen of fixed-duration ibrutinib plus venetoclax as first-line treatment for older or unfit patients with chronic lymphocytic leukemia (CLL) showed superior efficacy compared with chlorambucil and obinutuzumab.1Kostas Stamatopoulos, MD, PhD, of the Centre for Research and Technology Hellas in Thessaloniki, Greece, discussed the relevance of these findings for The ASCO Post.

“Obviously, this is a very promising development in view of a chemotherapy-free future for patients with CLL requiring treatment. However, a few issues merit comment, particularly concerning the comparator arm,” Dr. Stamatopoulos pointed out.

“The combination of chlorambucil and obinutuzumab would not be considered optimal anymore for patients with an adverse biologic background (ie, those with unmutated IGHV genes and/or deletion of chromosome 11q),” he said. “Along these lines, it is relevant to mention that chlorambucil/obinutuzumab has already been found to be inferior to the combination of venetoclax and obinutuzumab, another fixed-duration regimen for patients with CLL and coexisting conditions, in the CLL14 trial of the German CLL Study Group.”2

“A note of concern is also warranted regarding the incidence of serious adverse events with combined ibrutinib and venetoclax, which was higher than that observed in the comparator arm,” Dr. Stamatopoulos continued. However, he added, despite this finding, the overall safety profiles of the two regimens were not significantly different.

“These concerns notwithstanding, GLOW definitely expands the knowledge base on how to treat patients with CLL in the first-line setting using combinations of novel agents toward more effective disease control,” Dr. Stamatopoulos concluded. “More generally, such knowledge will pave the way to a novel therapeutic paradigm for CLL that would be time-limited, rather than fixed-duration, tailored to individual patients also on the basis of the quality of attained responses (ie, the status of minimal residual disease).” 

DISCLOSURE: Dr. Stamatopoulos reported relationships with AbbVie, AstraZeneca, Janssen, and Roche/Genentech.


1. Kater A, Owen C, Moreno C, et al: Fixed duration ibrutinib and venetoclax versus chlorambucil plus obinutuzumab for first-line chronic lymphocytic leukemia: Primary analysis of the phase 3 GLOW study. European Hematology Association 2021 Virtual Congress. Abstract LB1902. Presented June 12, 2021.

2. Fischer K, Al-Sawaf O, Bahlo J, et al: Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med 380:2225-2236, 2019.

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Fixed-duration ibrutinib and venetoclax as a first-line treatment yielded superior outcomes compared with chlorambucil plus obinutuzumab in patients with chronic lymphocytic leukemia (CLL), based on the primary analysis of the phase III GLOW trial presented during the European Hematology...