ASH 2021 | The future of fixed-duration therapy in CLL
Paolo Ghia, MD, Università Vita-Salute San Raffaele, Milan, Italy, comments on the efficacy of fixed-duration treatment in chronic lymphocytic leukemia (CLL). Numerous trials including the Phase III GAIA/CLL13 trial (NCT02950051), which assessed standard chemoimmunotherapy versus a combination of ibrutinib, obinutuzumab, rituximab, and venetoclax, and the Phase III CLL14 trial (NCT02242942), which investigated venetoclax and obinutuzumab, have shown fixed-duration treatment to result in undetectable MRD (uMRD) in a majority of patients. Data from the Phase II CAPTIVATE trial (NCT02910583) of ibrutinib and venetoclax additionally demonstrated that a long-term durable response is achievable even if patients do not achieve uMRD. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
There are a number of studies that explore fixed duration treatment in CLL. The first one being, of course, venetoclax plus obinutuzumab compared to chlorambucil plus obinutuzumab in the CLL14 study. There’s been a number of studies investigating the combination of ibrutinib plus venetoclax or other BTK inhibitors plus venetoclax. At ASH this year, we also saw the initial results of the GAIA study, where chemotherapy was compared to venetoclax plus rituximab or obinutuzumab, or the triplet combination of venetoclax plus ibrutinib plus obinutuzumab...
There are a number of studies that explore fixed duration treatment in CLL. The first one being, of course, venetoclax plus obinutuzumab compared to chlorambucil plus obinutuzumab in the CLL14 study. There’s been a number of studies investigating the combination of ibrutinib plus venetoclax or other BTK inhibitors plus venetoclax. At ASH this year, we also saw the initial results of the GAIA study, where chemotherapy was compared to venetoclax plus rituximab or obinutuzumab, or the triplet combination of venetoclax plus ibrutinib plus obinutuzumab. The data is very interesting because already with the doublet, but also with the triplet, we can achieve undetectable MRD in the vast majority of patients. In the GAIA study, the most recent data really approaches 90% of the patients being undetectable in bone marrow. It still remains to be assessed and validated in the long run how this translates in longer progression-free survival.
The initial data of the CAPTIVATE study where indeed patients were treated with ibrutinib plus venetoclax and there is now a follow-up up to two or three years, it shows that even patients who do not achieve undetectable MRD may obtain durable responses with time. This, again, probably questioning the real use and need of achieving undetectable MRD when patients are treated with the right combination of two or three drugs. But of course, for the clinical application, we have to wait still a little bit and probably the approval of ibrutinib plus venetoclax in fixed duration will be soon available at least in the western countries.
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