Extended Ibrutinib-Venetoclax Schedule Achieves 53% Undetectable MRD in Relapsed CLL
The SAKK 34/17 phase 2 trial evaluated a modified ibrutinib-venetoclax regimen in 30 relapsed/refractory CLL patients, extending ibrutinib lead-in to 6 months and combination treatment to at least 24 months. This schedule achieved undetectable MRD (10-4) in both bone marrow and peripheral blood in 53.3% of patients by intention-to-treat, with a 30-month PFS rate of 89.9%, supporting prolonged fixed-duration targeted therapy guided by MRD endpoints.
The original study
Ibrutinib lead-in followed by venetoclax plus ibrutinib for relapsed/refractory chronic lymphocytic leukemia: the SAKK 34/17 trial.
- Authors
- Condoluci A, Romano I, Dietrich D, Pini K, Stüssi G, Müller G, et al.
- Journal
- Blood
- Type
- Journal Article, Clinical Trial, Phase II, Multicenter Study
- PMID
- 40009495
Original abstract
The combination of ibrutinib plus venetoclax (IV) in chronic lymphocytic leukemia (CLL) treatment leverages their complementary mechanisms of action. Studies investigating IV typically begin with a short initial course of ibrutinib, followed by venetoclax introduction for a limited duration, typically 12 months. The Swiss Group for Clinical Cancer Research (SAKK) 34/17 study is a single-arm, multicenter, phase 2 trial evaluating the effectiveness of a modified IV schedule in patients with relapsed/refractory (R/R) CLL. No prior exposure to BTK or BCL2 inhibitors was allowed. The lead-in phase with ibrutinib was extended to 6 months to reduce the tumor burden and related tumor lysis syndrome (TLS) risk. Additionally, the treatment phase with IV is prolonged to a minimum of 24 months to enhance the undetectable minimal residual disease (uMRD; 10-4) rate. The primary end point was the rate of complete response or complete response with incomplete bone marrow recovery (CR/CRi) with uMRD in both bone marrow (BM) and peripheral blood (PB). Secondary end points included assessing the proportion of patients transitioning to a low-risk category for TLS after receiving ibrutinib lead-in. Of the 30 enrolled patients with R/R CLL, 40.0% achieved uMRD CR/CRi by intention-to-treat analysis, and 53.3% showed uMRD in the BM and PB. After the lead-in period with ibrutinib, 57.1% of patients achieved a low risk of TLS. At cycle 31, the progression-free survival rate was 89.9%. These results contribute to the increasing body of evidence supporting the idea that a longer IV duration is beneficial for enhancing therapeutic effectiveness. This trial was registered at www.clinicaltrials.gov as #NCT03708003.