DP078 | DISEASE MONITORING BY 8-COLOR FLOW CYTOMETRY ON PERIPHERAL BLOOD AT DIAGNOSIS OF MANTLE CELL LYMPHOMA IN THE PROSPECTIVE FIL VR-BAC STUDY

Assessment of minimal residual disease (MRD) in peripheral blood (PB) at the time of diagnosis may be clinically informative in patients with mantle cell lymphoma (MCL). Flow cytometry (FC) has been widely used for differential diagnosis, but its clinical role remains undefined, as its applicability for MRD evaluation compared to real-time quantitative polymerase chain reaction (RQ-PCR). In this FIL prospective study, we performed FC on PB of 128 consecutive treatment-naive patients with MCL enrolled in the VR-BAC trial, and compared results with those obtained by RQ-PCR. Two 8-color panels were used to characterize MCL clones (CD20/CD23/CD5/CD19/CD200/CD62L/CD3/CD45; kappa/lambda/CD5/CD19/CD305/CD11a/CD3/CD45) at diagnosis and in four further time-points. Patients were treated upfront with 4-6 R-BAC500 cycles, and patients with high-risk disease (HR) were consolidated with venetoclax monotherapy. Overall, 108 patients (84%) had a detectable clone by FC on PB at lymphoma diagnosis. The presence of a detectable clone did not correlate with any clinical variable, nor with HR features, such as histological variant, TP53 mutation or deletion, or proliferation index, but was associated with positive bone marrow biopsy (p<0.0001), as expected. With 20% cut-off, most patients were negative for CD200 (92%), CD23 (78%), and CD11a (86%), while 43% were CD305 positive. A significant association was found between the presence of CD19+ cells (p=0.03), or CD19+/CD5+ (p=0.04) in the PB at lymphoma diagnosis and inferior progression-free survival (PFS). This association was more pronounced in low-risk patients, defined as Ki67<30%, classical morphology, or TP53 wild-type. A total of 59 PB samples were investigated at diagnosis for MRD in parallel by FC and RQ-PCR. Only four samples (7%) had a positive RQ-PCR signal, but were negative by FC, with a positive predictive value for FC of 98%, and a true-positive-rate of 93%. Achieving a negative MRD by FC both after induction (14% still positive samples, p=0.0002) and after consolidation with venetoclax (11% still positive samples, p=0.03), was strongly associated with longer PFS. Accordingly, patients with a positive FC MRD sample at any of the four time points along study protocol had significantly inferior PFS (p<0.0001), irrespective of TP53 mutations or any of the HR features. In conclusion, FC MRD detection in MCL is a complementary tool to RQ-PCR, and a promising approach for therapeutic management and predicting outcomes.