Final CAPTIVATE Results Highlight Long-Term Outcomes in CLL

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, final results from the CAPTIVATE trial (NCT02910583) provided a comprehensive view of long-term outcomes for previously untreated patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treated with fixed-duration ibrutinib (Imbruvica) and venetoclax (Venclexta). The data not only reinforce earlier findings of durable benefit but also offer new insights into subgroup outcomes, retreatment efficacy, and minimal residual disease (MRD) dynamics.

In an interview with Targeted Oncology™, 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 implications of these long-term findings.

“The final analysis is, on one side, confirming with longer follow-up the very good data that we already showed before, with the benefit in terms of progression-free survival [PFS] and overall survival [OS] of our patients. In particular, what we now show very clearly is the subgrouping of the patient. So, we analyzed the progression-free survival and overall survival in patients based on the mutational status of the immunoglobulin,” says Ghia.

A key highlight of the final analysis was the stratification of PFS and OS based on immunoglobulin heavy-chain variable region mutational status and TP53 aberrations.

“Patients with mutated immunoglobulin genes had the highest benefit, with 80% of the patients still not progressing after 5.5 years. Then, patients with unmutated immunoglobulin genes did not reach a median progression-free survival after 5.5 years, though here only 53% of the patients will not need treatment, or will not progress, after 5.5 years,” adds Ghia.

He also notes that TP53-aberrant patients, a high-risk group defined by del(17p) or TP53 mutations, had the shortest benefit duration, with a median PFS already reached and only 30% progression-free at 5.5 years.

Importantly, the trial also provided evidence for the effectiveness of retreatment, and safety data continued to show no new signals with extended follow-up. Secondary malignancies remained infrequent, with non-melanoma skin cancers being the most common.

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