ASH 2022 | The GLOW study: MRD kinetics among patients with high-risk factors treated with Ibr+Ven versus Clb+O
Arnon Kater, MD, PhD, University of Amsterdam, Amsterdam, Netherlands, comments on the results from the GLOW study (NCT03462719) which assessed measurable residual disease (MRD) and outcomes of finite treatment with ibrutinib plus venetoclax (Ibr+Ven) and chlorambucil plus obinutuzumab (Clb+O) in high-risk patients with chronic lymphocytic leukemia (CLL). This study demonstrated that patients with unmutated IGHV in the Clb+O arm relapsed more quickly than patients in the Ibr+Ven arm, and showed a survival advantage for patients treated with Ibr+Ven. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.
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Transcript (edited for clarity)
So the GLOW study is the Phase III study, where elderly patients were randomized first-line treatment CLL against chlorambucil plus obinutuzumab standard treatment, or venetoclax and ibrutinib. And importantly, this is a finite treatment. So it’s not ibrutinib until relapse, but it is 15 cycles total, or from 12 cycles combination of venetoclax and ibrutinib. And we reported and published already the primary endpoint, which was progression-free survival, is a big difference...
So the GLOW study is the Phase III study, where elderly patients were randomized first-line treatment CLL against chlorambucil plus obinutuzumab standard treatment, or venetoclax and ibrutinib. And importantly, this is a finite treatment. So it’s not ibrutinib until relapse, but it is 15 cycles total, or from 12 cycles combination of venetoclax and ibrutinib. And we reported and published already the primary endpoint, which was progression-free survival, is a big difference.
But we now also have shown yesterday that the MRD curve, so what you see very interestingly is that different, I think, the venetoclax and obinutuzumab MRD curves are different with the combination of venetoclax in ibrutinib. Where more patients obtain undetectable MRD in unmutated cases, but also the MRD relapse is quicker in that patient. So we really have to rethink how to use MRD if you have to do it in this kind of studies.
Importantly, we also saw for the first time now an overall survival advantage in the study arm, venetoclax-ibrutinib. Which was not only due to earlier progressions, most of the patients received second line targeted agents who relapsed. But we saw actually more infections in the chlorambucil-obinutuzumab group. And we know from in vitro and mouse studies that it could be actually indeed the case that the venetoclax-ibrutinib combination is a stronger agent in overcoming the immune paralyzation that those patients have.
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Disclosures
Abbvie, Astra Zeneca, BMS, Janssen, Roche/Genentech: Research Funding; Janssen, LAVA: Patents & Royalties: Pending; Astra Zeneca, BMS, Roche/Gennetech, Janssen, Abbvie, LAVA: Membership on an entity’s Board of Directors or advisory committees; Abbvie, Astra Zeneca, Janssen: Other: Speakers fee; Amsterdam UMC, University of Amsterdam: Current Employment.
