ABSTRACT Measurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL) patients treated with venetoclax is a predictive factor of outcome in clinical trials. This multicenter prospective study was aimed to show the feasibility of MRD assessment in the real‐life setting and to confirm the results of clinical trials. Forty‐four patients were enrolled: 43% had 17p deleted and/or TP53 mutated (del17p/TP53mut), 62% had complex karyotype, and 65% of patients were previously treated with B‐cell receptor inhibitor (BCRi). MRD was evaluated by 8‐color flow cytometry (FC) on peripheral blood (PB) every 3 months from therapy start and samples with 10 −4 CLL cells were considered as undetectable (uMRD). PB‐uMRD patients were evaluated on bone marrow (BM). In 23 patients venetoclax was combined with Rituximab (VR). Median follow‐up was 39.47 months (range 31.02–43.32). Median number of PB samples for each patients was 5 (IQR 4–7). Undetectable MRD on PB at any timepoint was obtained in 34/40 patients (85%): 82% in venetoclax monotherapy (Vmono) and 86.9% in VR group. Concordance of PB/BM samples was 92% at 24 months. No significant difference in uMRD rates was detected based on del17p/TP53mut and number of previous therapies. Three‐year progression‐free survival (PFS) for Vmono and VR was 53.5% and 55%. Median PFS in del17pl/TP53mut was 29.8 and 34 months in Vmono and VR respectively. Landmark analysis based on 9‐month MRD showed a trend towards a better PFS in uMRD patients. Median PFS was 21.7 and 13.04 months in 24‐month uMRD and detectable MRD patients after VR, respectively (log rank p = 0.0309). In conclusion, in these high‐risk relapsed/refractory CLL patients who were MRD‐monitored in the context of a real‐life study the results were similar compared to published data in more selected patients.
Farina et al. (2026) studied this question.