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SOHO 2026 | Phase II PIVOT-CLL: pirtobrutinib, venetoclax, and obinutuzumab triplet vs doublet therapy in CLL
Nitin Jain, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the Phase II PIVOT-CLL study (NCT05536349) evaluating pirtobrutinib, venetoclax, and obinutuzumab as frontline therapy for patients with chronic lymphocytic leukemia (CLL). Dr Jain explains that triplet therapy can achieve deeper measurable residual disease (MRD) remissions than doublet regimens but increases myelosuppression and infection risk, making patient selection important. This interview took place at the 14th Annual Meeting of the Society of Hematologic Oncology (SOHO 2026) in Houston, TX.
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Transcript
So, you know, in the field of CLL, obviously, we have the doublets of ibrutinib and venetoclax. We also have doublets of ven-obinutuzumab, doublets of acalabrutinib-venetoclax. They’re all approved and used quite commonly. The PIVOT-CLL study is a triplet study, and it is incorporating pirtobrutinib, which is the non-covalent BTK inhibitor, so different from the covalent BTK inhibitor, such as ibrutinib, acalabrutinib, and zanubrutinib...
So, you know, in the field of CLL, obviously, we have the doublets of ibrutinib and venetoclax. We also have doublets of ven-obinutuzumab, doublets of acalabrutinib-venetoclax. They’re all approved and used quite commonly. The PIVOT-CLL study is a triplet study, and it is incorporating pirtobrutinib, which is the non-covalent BTK inhibitor, so different from the covalent BTK inhibitor, such as ibrutinib, acalabrutinib, and zanubrutinib. It’s pirtobrutinib combined with venetoclax and obinutuzumab. It’s a time-limited approach for one year, with the possibility of continuing the second year of pirto plus venetoclax for patients who are MRD5 or higher positive in blood or bone marrow. Now, in terms of these are two different approaches, right, triplet versus doublet, we know from the results of the study so far from the PIVOT study, and also I would say from the AMPLIFY study and other triplet studies, that the triplet studies would generally lead to better or higher undetectable MRD remissions, both in blood and bone marrow, compared to in general with the doublet studies. And that’s what we saw in the context of the PIVOT-CLL study as well, that we were seeing very high rates of not just the 10 to the minus 4 sensitivity MRD negative remissions, but also at the minus 6 level remissions with the next-generation sequencing assay in both blood and bone marrow. We also know from the triplet studies in general, there is generally more myelosuppression, especially neutropenia, grade 3 or 4 neutropenia, which again we saw in the PIVOT-CLL study. And I would also say that there is some increased risk of infectious complications in the context of triplet studies as opposed to the doublet study. So I believe it’s a bit of a trade-off. You certainly get deep levels of MRD undetectable remissions with the use of triplet studies, but you have to be careful about infections and kind of patient selection if you’re going to use triplet for an individual patient.
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