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ASH 2021 | GLOW: Assessing ibrutinib plus venetoclax in CLL

Carsten Niemann, MD, PhD, Copenhagen University Hospital, Copenhagen, Denmark, discusses findings in the Phase III GLOW trial (NCT03462719), which assessed first-line ibrutinib plus venetoclax versus chlorambucil with obinutuzumab in patients with chronic lymphocytic leukemia (CLL). Patients receiving ibrutinib and venetoclax reported lower rates of relapse, and Dr Niemann suggests intermediate minimal residual disease (MRD) as an acceptable endpoint for certain patients. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Transcript (edited for clarity)

The GLOW study is testing in the front-line setting. We’re combining the two targeted agents, the BCL-2 inhibitor venetoclax and the BTK inhibitor ibrutinib. If it could outperform chlorambucil and obinutuzumab for frail patients. We saw the first analysis of these data at the EHA in 2021, and now it ASH 2021, what we are seeing is following these patients in terms of minimal residual disease...

The GLOW study is testing in the front-line setting. We’re combining the two targeted agents, the BCL-2 inhibitor venetoclax and the BTK inhibitor ibrutinib. If it could outperform chlorambucil and obinutuzumab for frail patients. We saw the first analysis of these data at the EHA in 2021, and now it ASH 2021, what we are seeing is following these patients in terms of minimal residual disease. And what is really interesting here is to see that patients treated with ibrutinib-venetoclax, whether they achieve undetectable MRD, and even 10-5 or 10-6 levels tested by NGS, or if they have intermediate MRD levels, they actually continue at a, more or less, stable level, at least for 12 months after starting therapy. And this is different from what we saw in the chlorambucil-obinutuzumab arm.

Thus, it seems that targeting the CLL disease by two different agents, where we know they have different mechanisms of action and that they also target the different compartments, the lymph nodes, the bone marrow, and the peripheral blood of the disease differently, may actually have a prolonged effect in terms of keeping the disease, even if it’s visible like the intermediate MRD levels, keeping the disease maybe as a premalignant monoclonal B lymphocytosis and BL states. It might not be that we just need to aim for the undetectable MRD levels, it might be actually for some patients good enough to get into intermediate MRD levels because they’ll stay stable for long periods of time after stopping therapy. Thus, this is the next step to towards targeted time-limited therapy and CLL, I believe.

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