Project description:In chronic lymphocytic leukemia, measurable residual disease (MRD) depth following fixed-duration treatment is associated with progression-free survival (PFS). Often, MRD is reported as a static parameter, but successive MRD measurements may more accurately capture MRD dynamics and reveal valuable prognostic information. We used our recently developed IGHV leader-based NGS assay to measure MRD at four timepoints in 60 patients treated in the HOVON-139/GIVE trial, in which previously untreated patients received one year induction treatment with obinutuzumab and venetoclax, followed by randomization to consolidation treatment with venetoclax or MRD-conditional consolidation. Induction treatment resulted in MRD undetectability (<10-5) in 93% of assessed patients, with 85% and 74% of patients retaining MRD undetectability at six and twelve months after randomization. Uniquely, we measured MRD at a very early timepoint, during the fourth week of venetoclax ramp-up after obinutuzumab pre-induction. Here, MRD levels showed large interindividual variation, and, importantly, were associated with the probability of achieving MRD undetectability after induction treatment, MRD conversion after randomization and PFS. Additionally, the IGHV leader-based NGS assay allows characterization of the healthy background IGHV repertoire. Of note, venetoclax consolidation treatment, compared to no consolidation treatment, significantly impaired polyclonal IGHV repertoire reconstitution after induction treatment with venetoclax and obinituzumab.

2024-03-01 | GSE225043 | GEO

Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy.

Project description: Not available

| S-EPMC5279834 | biostudies-literature

The expanding role of venetoclax in chronic lymphocytic leukemia and small lymphocytic lymphoma.

Project description: Not available

| S-EPMC6859801 | biostudies-literature

New developments in the treatment of chronic lymphocytic leukemia: role of obinutuzumab.

Project description: Not available

| S-EPMC4524526 | biostudies-literature

Acalabrutinib plus Obinutuzumab in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia.

Project description: Not available