Research presented at the 2021 ASH Annual Meeting suggests that patients with relapsed/refractory chronic lymphocytic leukemia (CLL) suggests that measurable residual disease (MRD)–guided, time-limited treatment with ibrutinib and venetoclax demonstrates a favorable benefit-risk profile. This is according to a study by Carsten Utoft Niemann, MD, PhD, from Copenhagen University Hospital in Denmark, and colleagues.
The researchers added that no new safety signals were detected in the trial, and no patients had disease progression after treatment cessation. Patients who became MRD-positive were able to successfully reinitiate therapy, the authors added, “thus proving MRD-guided cessation and re-initiation of targeted therapy feasible in CLL.”
Dr. Niemann and colleagues evaluated progression-free survival (PFS) in 225 patients with relapsed/refractory CLL at 12 months after MRD-guided treatment cessation of venetoclax plus ibrutinib treatment, with the option to reinitiate the combination on MRD reappearance.
Patients who were BTK inhibitor-naïve received ibrutinib lead-in at a dose of 420 mg daily for two 28-day cycles. Venetoclax ramp-up was initiated during cycle 3, reaching 400 mg daily at cycle 4 with continued venetoclax plus ibrutinib during cycles 4 through 15. At cycle 15, 36% of patients achieved undetectable MRD in peripheral blood or bone marrow. The overall response rate was 86%, which included a rate of complete response with incomplete hematologic recovery of 64%.
Next, patients reaching at least partial remission (PR) and undetectable MRD at day 15 of cycle 15 were randomized 1:2 to receive ibrutinib maintenance (arm A) or treatment cessation (arm B). Patients in arm B who did not achieve undetectable MRD continued ibrutinib maintenance without randomization.
The researchers concluded that the primary endpoint of the trial was met, with 98% of patients in arm B achieving PFS at 12 months after randomization. They added that no difference in undetectable MRD at cycle 15 was seen between TP53 aberrated/wild-type patients or IGHV unmutated/mutated patients. The most frequent adverse event was infections (30%). Atrial fibrillation was reported for 29 patients (13%) during the first 15 cycles, while no patients under observation in arm B