Dr Ghia on the Role of Fixed-Duration Ibrutinib Plus Venetoclax in CLL and Beyond

“This is a very interesting combination that is very beneficial in CLL, so it has attracted a lot of attention in other [hematologic malignancies] where it is being explored.”

Paolo Ghia, MD, PhD, full professor of medical oncology at Università Vita-Salute San Raffaele and director of the Strategic Research Program on CLL at IRCCS Ospedale San Raffaele, discussed ongoing and future directions for the clinical investigation of fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) in chronic lymphocytic leukemia (CLL) and other hematologic malignancies.

The ibrutinib/venetoclax combination has shown substantial clinical benefit in patients with treatment-naive CLL and is now being evaluated for broader applicability, including in mantle cell lymphoma (MCL), Ghia emphasized. He explained that although the regimen is highly active in CLL, its role in other lymphoid malignancies—particularly MCL—requires further study given the disease’s distinct biological behavior and therapeutic goals. Investigators are currently examining how the combination or sequencing of these agents may be optimized in other disease settings. He noted that evaluations have explored the use of combination in patients Waldenström macroglobulinemia, although mixed results to this point have prompted the need for additional work in that space.

Looking ahead, retreatment with ibrutinib and venetoclax following disease progression after fixed-duration therapy represents a key area of interest. Ghia noted that this retreatment strategy is central to the appeal of time-limited regimens and will be evaluated in future studies. The ability to reintroduce ibrutinib and venetoclax without significant cross-resistance or cumulative toxicity could allow for re-use of the regimen as an effective salvage approach in select patients with relapsed disease.

Ghia concluded that although fixed-duration ibrutinib plus venetoclax continues to establish itself as a standard first-line option in CLL, prospective evaluation is needed to define its role in other B-cell malignancies and in the context of retreatment. These analyses will provide essential data on long-term durability, sequencing strategies, and the feasibility of re-treatment with this doublet.