Dr Ghia on Long-Term Benefits of Fixed-Duration Ibrutinib/Venetoclax in CLL

Paolo Ghia, MD, PhD, deputy director of the Division of Experimental Oncology at San Raffaele Scientific Institute in Milan, Italy; full professor of medical oncology; a group leader in the B-cell Neoplasia Unit; and the head of the Strategic Research Program on CLL at the Università Vita Salute San Raffaele, discusses the main takeaways from the final analysis of the phase 2 CAPTIVATE study (NCT02910583) which were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

CAPTIVATE demonstrated the long-term efficacy and safety of fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) when used for patients with previously untreated chronic lymphocytic leukemia (CLL). With long-term follow-up, the combination elicited durable progression-free survival rates and overall survival rates in patients with CLL, including patients with high-risk genomic features.

According to findings from the final analysis, 73% (95% CI, 66.0%–79.0%) of patients remained treatment-free 5.5 years after completing just 15 months of therapy, and the regimen was well tolerated, with no new safety signals observed. Patients with mutated IGHV had the most durable responses, but even high-risk patients, including those with TP53 abnormalities, showed meaningful benefit. Further, retreatment safety profiles were consistent with prior data.

“The ibrutinib plus venetoclax is safe. No safety signals have been seen, even with the retreatment of the patient. Second, the responses are durable. We have a median progression-free survival that has not been reached after 5.5 years, and a time to next treatment which is much longer,” explains Ghia, in an interview with Targeted Oncology^.

Additionally, minimal residual disease (MRD) status at the end of treatment was the strongest predictor of long-term outcomes, reinforcing the value of full-course therapy before making clinical decisions.

“MRD is predictive of long-term durable responses only if assessed at the end of treatment,” adds Ghia.

REFERENCE:

Ghia P, Barr PM, Allan JN, et al. Final analysis of fixed-duration ibrutinib + venetoclax for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in the phase 2 CAPTIVATE study. J Clin Oncol. 2025;43(suppl 16):7036-7036. doi: 10.1200/JCO.2025.43.16_suppl.7036