Dr Ghia on Potential Future Roles for Ibrutinib Plus Venetoclax in CLL

“We will hopefully study this combination in the retreatment of patients who have already been treated with routine ibrutinib plus venetoclax. This is something that we have to explore in the future, because the key to a fixed-duration treatment is the possibility of retreating the patient with exactly the same treatment.”

Paolo Ghia, MD, PhD, full professor, medical oncology, Università Vita-Salute San Raffaele; head, Laboratory of B-Cell Neoplasia, director, Strategic Research Program on CLL, ORCCS Ospedale San Raffaele, discusses future research directions and potential roles for first-line, fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) in patients with chronic lymphocytic leukemia (CLL) and other hematologic malignancies.

A pooled analysis of the phase 3 GLOW trial (NCT03462719) and the fixed-duration cohort of the phase 2 CAPTIVATE study (CAPTIVATE-FD; NCT02910583) evaluated overall survival (OS) outcomes for 265 patients (GLOW, n = 106; CAPTIVATE-FD, n = 159) with CLL treated with fixed-duration ibrutinib plus venetoclax. Findings presented at the 2024 ASH Annual Meeting demonstrated that overall survival estimates in this patient population were comparable with those of an age-matched general European population across various age groups and regardless of immunoglobulin gene mutation status.

The combination of ibrutinib and venetoclax has shown significant efficacy in CLL, prompting interest in its potential applications in other malignancies, Ghia begins. For instance, studies in mantle cell lymphoma, a more aggressive disease, indicate that understanding the sequence or value of the combination in this context remains critical, he notes. Conversely, investigations in Waldenström macroglobulinemia have yielded mixed results, emphasizing the need for further studies with larger patient cohorts to clarify the combination’s role in this setting, Ghia adds.

Future research may also focus on retreatment with ibrutinib plus venetoclax in patients previously treated with these agents, Ghia continues. Exploring the efficacy and safety of this fixed-duration approach in relapsed settings is key to optimizing treatment strategies and extending the benefits observed in CLL to other disease contexts, he concludes.