P074 | Innovative MRD detection and immune profiling in relapsed CLL treated with rituximab-venetoclax: insights from the “Dedalus” protocol

Abstract

Introduction. Fixed-duration Rituximab (R) and Venetoclax (Ven) therapy has improved outcomes in chronic lymphocytic leukemia (CLL), achieving a 7-year overall survival of 69.6% and effective MRD eradication. Accurate minimal residual disease (MRD) assessment is essential to monitor treatment response. The “Dedalus” protocol compared MRD detection by flow cytometry (MFC) and next-generation sequencing (NGS) in relapsed/refractory CLL patients treated with R-Ven and explored correlations with clinical outcomes and immune changes.
Methods. Twenty-two patients underwent MRD assessment using ERIC-compliant MFC and Lymphotrack NGS (sensitivity 10−5). Advanced ultrasound monitored treatment response. MRD and immunological parameters were evaluated at 1, 6, 12, and 18 months or upon treatment discontinuation.
Results. Twenty patients achieved complete remission (CR), with MRD undetectable in 15 at first assessment by both methods. In two partial response cases, NGS detected residual IgH clonality (3–45 clonal cells per 10⁶) missed by MFC (Figure 1). Detection thresholds were 10^-4 (MFC) and 10^-5 (NGS). Venetoclax caused sustained B cell depletion and reduced CD4+ T cells, altering the CD4/CD8 ratio in 25% of patients. NGS results correlated more closely with clinical outcomes, especially in low-level residual disease.
Conclusions. R-Ven is highly effective in achieving durable remissions in relapsed CLL. While MFC is accessible and cost-effective, NGS offers superior sensitivity and better correlation with outcomes. Future studies should evaluate digital PCR for IgH rearrangements as a non-invasive MRD biomarker and further investigate Venetoclax’s immunomodulatory effects.