Dr Ghia on the Implications of Data From CAPTIVATE for Fixed-Duration Ibrutinib Plus Venetoclax in CLL/SLL

"At the end of the day, we designed the CAPTIVATE study…to aim at a fixed-duration treatment because we think it [provides] an advantage for…everyone involved. Still…we are not curing the patient; we are [providing] a shorter [treatment] period so that the patient can benefit [from] a longer off-therapy period, [but will] then need to retreat them."

Paolo Ghia, MD, a full professor of medical oncology at the Università Vita Salute San Raffaele and director of the Strategic Research Program in CLL at IRCCS Ospedale San Raffaele, discussed the implications of data from the final analysis of the phase 2 CAPTIVATE study (NCT02910583), which evaluated pirtobrutinib (Jaypirca) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had previously received a covalent BTK inhibitor, for treatment sequencing and the use of retreatment strategies in clinical practice.

In the overall patient population (n = 202) of the CAPTIVATE study, the progression-free survival (PFS) rate at 5.5 years was 66% (95% CI, 58%-72%), and the overall survival rate reached 97% (95% CI, 93%-99%). Ghia emphasized that these updated data reinforce the long-term PFS benefit of a fixed-duration, all-oral combination of ibrutinib plus venetoclax for the frontline treatment of patients with CLL/SLL.

These robust results contributed to the European Commission's approval of this fixed-duration regimen for frontline CLL treatment in August 2022, which was also supported by data from the phase 3 GLOW trial (NCT03462719).

Ghia underscored that fixed-duration treatment offers substantial advantages for patients, payers, and physicians by providing a structured period of therapy followed by an extended off-therapy interval, enhancing patient quality of life and managing healthcare costs. He clarified that while fixed-duration approaches are highly beneficial, they are not curative, as patients are expected to eventually relapse. A critical component of this strategy is the ability to preserve subsequent therapeutic options for when relapse eventually occurs, Ghia explained.

However, Ghia highlighted a significant challenge in clinical practice: in many countries, the necessary retreatment with these agents is not approved or reimbursed. This lack of access or reimbursement, "weakens the whole idea of the fixed-duration treatment" by limiting a clinician's ability to offer sustained benefit to patients and manage their disease progression effectively, he stressed.