Thread by @Othman_Al_Sawaf

Delighted to share our latest paper in #JCO, in which we suggest an MRD growth model of CLL, including new data from the CLL14 study (Ven-Obi vs Clb-Obi). #leusm #GCLLSG @ASCO_pubs

bit.ly/2ZyAVEZ

Some results in a quick 🧵 1/n

1.) We used NGS-based MRD quantification of >2,000 PB samples to devise a non-linear mixed effects model for outlining MRD growth after tx. There was wide heterogeneity in MRD growth trajectories that was dependent on various clinical, serological and genetic characteristics.

2.) Notably, one of the most important determinant of MRD growth was actually the choice of therapy: Patients who received Ven-Obi had a signif longer MRD doubling time and time to MRD conversion than pts who received chemo with Clb-Obi.

3.) This translated into a signif longer PFS for Ven-Obi treated pts - at 4 years, 74% of pts in the Ven-Obi arm were still in remission.

4.) Using this method, we are able to identify factors associated with quicker growth - these included high-risk genomics like TP53 aberrations or unmutated IGHV. This was also associated with PFS.

5.) Clinically, the FD approach with BCL2 inhibitor venetoclax and CD20 antibody obinutuzumab is therefore feasible and effective in pts with treatment-naive CLL, particularly when considering the TTNT, with the majority of pts remaining treatment-free ≥3 after study treatment.

6.) Question reg contin vs FD tx for high-risk needs randomisation (->#CLL17). For now, the fact that mPFS is 4-5 years indicates that the FD approach is feasible also in high-risk dis. Pts can potentially be retreated (-> #ReVenG), so that they can also benefit from tx-free yrs.

7.) CLL14 is a huge team effort. Thank you to the pts & families, investigators, nurses & site staff who continue to support the study with such enthusiasm.

8.) Big thanks to the whole CLL14 team, especially Can Zhang, Tong Lu, Mike Liao, Yanwen Jiang, Michael Hallek and Kirsten Fischer for the fantastic work.

9.) Thank you to the funders and teams from Roche/Genentech, AbbVie and @dfg_public. Last but not least, thanks to the reviewers, @DrJFriedberg and the editorial team @ASCO_pubs for a very constructive and streamlined revision process!