Dose-modified, fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) generated responses in patients with previously untreated chronic lymphocytic leukemia (CLL) and met the primary end point of the phase 2 TAILOR study (NCT05963074), data from which were presented at the
In the reactive dose-adjustment cohort (cohort 1A; n = 86), treatment elicited an overall response rate (ORR) of 94.2% (95% CI, 87%-98%); in the proactive dose-adjustment cohort (cohort 1B; n = 85), the ORR was 89.4% (95% CI, 81%-95%). Both cohorts met their primary end point with a statistically significant improvement in ORR vs a prespecified benchmark of greater than 75%. The 12-month progression-free survival (PFS) and overall survival (OS) rates were both 98.8% in cohort 1A, and were 97.6% and 98.8%, respectively, in Cohort 1B; 1 patient in each cohort experienced progressive disease.
“When treated both per dose adjustment guidance [per prescribing information] and with proactive dose reductions, patients had manageable adverse effect [AE] profiles, including low rates of atrial fibrillation and no cardiac deaths,” lead study author Paolo Ghia, MD, PhD, of the medical school at Universita Vita-Salute San Raffaele in Milan, Italy, and colleagues wrote in a poster presentation of the data. “Results from TAILOR further strengthen the clinical profile and dosing flexibility of ibrutinib plus venetoclax in previously untreated CLL.”
TAILOR is the first study to prospectively evaluate two clinical strategies intended to improve the tolerability of fixed-duration ibrutinib plus venetoclax: reactive dose adjustment per label and proactive dose adjustment.
Dose-reduction guidance has been incorporated into ibrutinib prescribing information, and the clinical interest in tolerability-driven approaches reflects the substantial treatment burden documented in this population, particularly among older patients.²
The study included patients with previously untreated CLL, and they were evaluated for TP53 status at screening.1 Patients were not allowed to have significant cadiovascular history, uncontrolled hypertension, or an ECOG performance status higher than 2.
After physicians determined that patients were appropriate to receive ibrutinib plus venetoclax, patients were randomly assigned 1:1 to the reactive (cohort 1A) and proactive (cohort 1B) dose-adjustment regimens. Patients were dosed per the approved label for 12 cycles of fixed-duration therapy following a 3-cycle lead-in with ibrutinib at 420 mg daily. Venetoclax step-up and dosing followed the label. In Cohort 1B, the ibrutinib dose was proactively reduced to 280 mg daily after the lead-in.
The primary end point was ORR, tested individually for each cohort against the greater-than-75% benchmark. Secondary end points included PFS, OS, and safety.
As of November 2025, 95.3% of patients in Cohort 1A and 94.1% in Cohort 1B remained on study, while 1.2% in each cohort had completed treatment.
Both cohorts demonstrated consistent treatment benefit in ORR across patient subgroups, including patients with del(17p)/TP53 aberrations.
In cohort 1A, any-grade and grade 3 or higher treatment-emergent AEs (TEAEs) were reported in 95.3% and 48.2% of patients, respectively; after the ibrutinib lead-in, these respective rates were 91.8% and 41.2%. AEs led to ibrutinib discontinuation in 4.7% of patients and ibrutinib dose reduction in 20.0%. One death, due to intracranial hemorrhage, was deemed related to ibrutinib. AEs of interest included infections and infestations (51.0%), arthralgia (21.2%), hypertension (10.6%), and atrial fibrillation (4.7%).
In cohort 1B, any-grade and grade 3 or higher TEAEs were reported in 94.1% and 50.6% of patients, respectively; after the ibrutinib lead-in, these respective rates were 83.5% and 42.4%. AEs led to ibrutinib discontinuation in 11.8% of patients and ibrutinib dose reduction in 11.8%. One death, due to pneumonia during the lead-in, was reported. AEs of interest included infections and infestations (31.8%), arthralgia (17.6%), hypertension (16.5%), and atrial fibrillation (8.2%).
