B-227 Customized molecular tests for minimal residual disease: a tool for therapeutic decisions in follicular lymphoma patients

Abstract Background Monitoring of minimal residual disease (MRD) is based on accurate laboratory tests which can recognize a small fraction of malignant cells that survived the course of treatment. Several studies of the B-non-Hodgkin lymphoma group have been presented that MRD positivity at the end of treatment is a negative prognostic index. Follicular lymphoma (FL) is a chronic indolent malignancy, which response highly to immuno-chemotherapy followed by prolonged remissions but with inevitable relapse in most patients. The GALLIUM study showed that immuno-chemotherapy combinations, 6 cycles of bendamustine-obinutuzumab (BO), is the most efficacious treatment, but with severe side effects .In addition, 90% of patients achieved negative MRD from peripheral blood (PB) or bone marrow (BM) after only 3 BO cycles. These findings raise the possibility for MRD based treatment approach, where the duration of chemotherapy could be decided according to MRD status at mid-induction (MI). Identification of a marker in the PB and/or BM of each FL patient which will be use to the design of a sensitive RQ-PCR test for MRD detection for follow-up. Methods Qualitative PCR for translocation 14:18 and for the VDJ rearrangement sequence of the immunoglobulin heavy chain was used for marker identification. MRD monitoring was done by RQ-PCR. MRD monitoring for VDJ was designed specifically to each patients based on his VDJ sequence. MRD was assessed on PB and BM at MI. Results Marker for monitoring was identified at 11/21 patients in this study. After 3 combined therapy cycles, 7 patients were found to have MRD negativity by RQ-PCR therefore continue with immuno-therapy only. MRD positivity was assessed in BM of 3 patients (0.11%, 0.022%, and 0.133%). These 3 patients continued with the combined therapy. RQ-PCR sensitivity was 10-4-10-5. Conclusions This study will reveal the ability to use sensitive and specific MRD that has to be designed for each patient according to his marker and enable the establishment of a treatment with a high safety profile for FL patients. Correlation between MRD status and clinical and safety parameters will be assessed at the end of the study, 30 months after the first treatment, taking into account MRD status from different time point of the follow-up period.