Dr Ghia on the Efficacy of Fixed-Duration Ibrutinib Plus Venetoclax in CLL/SLL

“What we have shown in the fixed-duration cohort is that after 5.5 years, the PFS was 60%. We [have] not yet reached the median PFS [with up to 7 years of follow up].”

Paolo Ghia, MD, PhD, a full professor in medical oncology at Università Vita-Salute San Raffaele, director of the Strategic Research Program on CLL, and head of the Laboratory of B-Cell Neoplasia at the IRCCS Ospedale San Raffaele, discussed the efficacy of fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) for the treatment of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The final analysis of the phase 2 CAPTIVATE trial (NCT02910583) evaluated outcomes with fixed-duration ibrutinib plus venetoclax in the fixed-duration cohort and the placebo arm in the minimal residual disease (MRD) arm with up to 7 years of follow up. Of note, the final analysis focused on the fixed-duration cohort, as this modality has become standard globally, Ghia began. He noted that after 5.5 years in the fixed-duration cohort, the progression-free survival (PFS) rate was 60% (95% CI, 52%-68%), and the overall survival rate was 96% (95% CI, 91%-98%).

In the fixed-duration cohort, patients received 3 cycles of ibrutinib as lead-in therapy and subsequently were treated with 12 cycles of ibrutinib plus venetoclax. After follow-up and upon disease progression, patients could reinitiate ibrutinib-based therapy. Furthermore, patients in the MRD cohort were also treated with 3 cycles of ibrutinib as lead-in therapy and 12 cycles of ibrutinib plus venetoclax before MRD-guided randomization. Patients were then stratified based on whether they had confirmed undetectable MRD (uMRD) or unconfirmed uMRD. Those with confirmed uMRD were randomly assigned 1:1 to receive placebo or ibrutinib; those with unconfirmed uMRD were randomly assigned 1:1 to receive ibrutinib or ibrutinib plus venetoclax.

Notably, patients with CLL/SLL typically experience disease progression with most current therapies, Ghia emphasized. However, the data show that approximately one-third of patients were progression-free for more than 5 years after only receiving therapy for 15 months. In the future, it may be necessary to determine which patient subgroups will benefit most from receiving fixed-duration ibrutinib plus venetoclax compared with continuous ibrutinib, he concluded.