Minimal residual disease (MRD) assessment can be used to guide treatment discontinuation in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), according to phase 2 results published in the Journal of Clinical Oncology.
The phase 2 CAPTIVATE trial (ClinicalTrials.gov Identifier: NCT02910583) was designed to test MRD-guided treatment discontinuation after first-line ibrutinib plus venetoclax in patients with CLL/SLL.
The study enrolled 164 previously untreated patients. Their median age was 58 years (range, 28-69 years), 16% had del(17p), 17% had del(11q), 19% had complex karyotype, 12% had TP53 mutations, and 60% had unmutated IGHV.
All patients received 3 cycles of ibrutinib to start, and 148 went on to complete 12 cycles of combination ibrutinib and venetoclax.
A majority of patients (75%) achieved a best MRD response of undetectable MRD (uMRD) in the peripheral blood, and 68% achieved uMRD in the bone marrow.
Patients with confirmed uMRD were randomly assigned to receive placebo (43 patients) or ibrutinib (43 patients). Patients without confirmed uMRD were randomly assigned to ibrutinib (31 patients) or ibrutinib plus venetoclax (32 patients).
Survival Outcomes
The median follow-up was 31.3 months. The primary endpoint was 1-year disease-free survival (DFS) with placebo vs ibrutinib among patients with uMRD.
There was no significant difference in 1-year DFS between the placebo and ibrutinib arms — 95% and 100%, respectively (P =.15). The estimated 30-month progression-free survival (PFS) rates were the same as the 1-year DFS rates — 95% and 100%, respectively.
Among patients without confirmed uMRD, the estimated 30-month PFS rate was 95% with ibrutinib and 97% with ibrutinib plus venetoclax.
Safety Results
Tumor debulking with 3 cycles of ibrutinib significantly reduced the risk of tumor lysis syndrome (TLS). After the ibrutinib lead-in, 90% of patients with a high risk of TLS at baseline shifted to medium- or low-risk categories.
The frequency of adverse events (AEs) was highest during the first 6 months of pre-randomization treatment. The most common treatment-emergent AEs during this phase were diarrhea (71%), nausea (45%), and neutropenia (43%).
In patients with confirmed uMRD, the incidence of grade 3 or higher AEs decreased before and after randomization, and a greater reduction was seen in the placebo arm.
Among patients without confirmed uMRD, grade 3 or higher AEs were more common in the ibrutinib-venetoclax arm than in the ibrutinib arm.
Disclosures: This research was supported by Pharmacyclics LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Wierda WG, Allan JN, Siddiqi T, et al. Ibrutinib plus venetoclax for first-line treatment of chronic lymphocytic Leukemia: Primary analysis results from the minimal residual disease cohort of the randomized phase 2 CAPTIVATE study. J Clin Oncol. Published online October 7, 2021. doi:10.1200/JCO.21.00807