Longitudinal Monitoring of Measurable Residual Disease in Chronic Lymphocytic Leukemia Patients Treated With Venetoclax: Results of a Prospective Multicenter Real‐Life Study

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.