ASH 2021: Minimal Residual Disease Kinetics Identified as a Predictor of Zanubrutinib-Obinutuzumab-Venetoclax Treatment Response in CLL

Minimal residual disease (MRD) kinetics were found to be predictive of achievement and durability of undetectable MRD with zanubrutinib-obinutuzumab-venetoclax (BOVen) treatment in patients with chronic lymphocytic leukemia (CLL), according to trial results presented by LRF grantee Jacob D. Soumerai, MD of Massachusetts General Hospital Cancer Center.

In a multicenter, phase 2 trial funded in part by LRF and led by LRF Scientific Advisory Board (SAB) Immediate Past-Chair and current member Andrew D. Zelenetz, MD, PhD of Memorial Sloan Kettering Cancer Center, patients with previously untreated CLL received BOVen in 28-day cycles for eight to 24 cycles, until undetectable MRD in peripheral blood and bone marrow was achieved.

At a median 26 months of follow up, 33 out of 37 patients achieved undetectable MRD in peripheral blood. Undetectable MRD in bone marrow was observed in 33 patients at a median eight months, all of which discontinued treatment after a median 10 months. These results demonstrated a frequent and durable achievement of undetectable MRD in patients with CLL with BOVen treatment.

Additionally, a ≥400-fold reduction in peripheral blood MRD was found to be highly predictive of undetectable MRD in bone marrow within eight months. The median duration of treatment was consequently shorter in patients who achieved this metric (eight months vs 13 months for those who did not). However, researchers found that despite a shorter treatment duration, these patients experienced longer MRD failure-free survival.
The researchers suggested that further studies are needed to determine the utility of MRD kinetics as a biomarker to predict BOVen treatment duration.

This study also included contributions from LRF grantees Connie Batlevi, MD, PhD, and Anita Kumar, MD and Lia Palomba, MD of Memorial Sloan Kettering Cancer Center; LRF grantee P. Conner Johnson, MD of Massachusetts General Hospital Center; New England Lymphoma Rounds Steering Committee members Jeremy Abramson, MD and Jeffrey Barnes, MD, PhD of Massachusetts General Hospital Cancer Center; and New York Lymphoma Rounds Steering Committee member Anthony Mato, MD of Memorial Sloan Kettering Cancer Center.