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ASH 2024 | Atezolizumab combined with venetoclax and obinutuzumab for frontline CLL
Nitin Jain, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on the potential of combining atezolizumab, a humanized monoclonal anti–PD-L1 antibody, with venetoclax and obinutuzumab for frontline treatment of chronic lymphocytic leukemia (CLL). This regimen has shown high measurable residual disease (MRD)-negative remission rates in a Phase II study of 37 patients (NCT02846623), with some expected immune toxicity observed. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
So currently the frontline CLL therapy landscape for the time-limited approach is venetoclax plus obinutuzumab. But we also know that checkpoint inhibitors, such as previously our group has worked on nivolumab plus ibrutinib for Richter’s transformation and others have also looked at pembrolizumab. But atezolizumab is a PD-L1 antibody which we argued could be synergistic with venetoclax and obinutuzumab in a time-limited fashion for newly diagnosed patients...
So currently the frontline CLL therapy landscape for the time-limited approach is venetoclax plus obinutuzumab. But we also know that checkpoint inhibitors, such as previously our group has worked on nivolumab plus ibrutinib for Richter’s transformation and others have also looked at pembrolizumab. But atezolizumab is a PD-L1 antibody which we argued could be synergistic with venetoclax and obinutuzumab in a time-limited fashion for newly diagnosed patients. In this study, we have treated 37 patients at our institution. We are seeing high rates of MRD-negative remission in the bone marrow assessed by flow cytometry. However, we also saw some toxicity in terms of immune toxicity, which is not unexpected because of the immune checkpoint we are using.
Also in this analysis, which will be presented by my colleague, Dr. Patrick Ravel, we also did single cell RNA sequencing and we were able to show that there were immune subsets of patients who have higher certain subsets of CD8 T-cells they were likely to respond better compared to the others. Again this is an ongoing study we are continuing to follow patients long term and eventually we’ll have to see how this pans out compared to other targeted therapy combinations which me and others are exploring.
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Disclosures
Newave: Research Funding; TG Therapeutics: Consultancy, Honoraria, Other: Travel Support; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Dialectic Therapeutics: Research Funding; TransThera Sciences: Research Funding; Fate Therapeutics: Research Funding; Servier: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Aprea Therapeutics: Research Funding; Precision Biosciences: Consultancy, Honoraria, Other: Travel Support, Research Funding; NovalGen: Research Funding; ADC Therapeutics: Research Funding; Ipsen: Consultancy, Honoraria, Other: Travel Support; MEI Pharma: Consultancy, Honoraria, Other: Travel Support; Pharmacyclics: Consultancy, Honoraria, Other: Travel Support, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel Support; Genentech: Consultancy, Honoraria, Other: Travel Support, Research Funding; Cellectis: Consultancy, Honoraria, Other: Travel Support, Research Funding; CareDx: Consultancy, Honoraria, Other: Travel Support; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel Support, Research Funding; BeiGene: Consultancy, Honoraria, Other: Travel Support; AstraZeneca: Consultancy, Honoraria, Other: Travel Support, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Other: Travel Support, Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel Support, Research Funding; Incyte: Research Funding; Loxo Oncology: Research Funding; Medisix: Research Funding; MingSight: Honoraria, Research Funding.
