Updated results from a Phase II study of minimal residual disease-guided venetoclax + obinutuzumab for the initial treatment of fit patients with chronic lymphocytic leukemia

作者：Meghan C. Thompson, Anthony R. Mato, Andrew D. Zelenetz, Jae-Hong Park, Mark B. Geyer, Andriy Derkach, David Nemirovsky, Deborah M. Stephens, Catherine C. Coombs, Prioty Islam, Christopher E. Jensen, Lorenzo Falchi, Lia Palomba, Anita Kumar, Gilles Salles, Eytan M. Stein, Jennifer Kimberly Lue, Lauren Nogan, Bejal Kikani, Ryan Sutterby, Thu Quynh Nguyen, Alexandra M. Allen, Sumathy Sudhir, Gail Panton, Victoria L. Duffy, Dianna Tyznar, Jamila Brutus, Tenzin Nyima, Anmol Shah, Dhara Soni, Michael R. Silvestrone, Monica Shah, Miranda Harris, Megha Karnam, Claire Hutzler, Kevin A. David, Aaron D. Goldberg, Stephen E. Fleming, Giovanni Diaz, Habib Hamidi, Bita Fakhri, Lindsey E. Roeker · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-3902 · 被引用次数：1 · 研究领域：Chronic Lymphocytic Leukemia Research、CAR-T cell therapy research、HER2/EGFR in Cancer Research

Abstract Background: Undetectable minimal residual disease (uMRD) at the end of first-line (1L) treatment (tx) with 12-cycles (C) of venetoclax (ven) + obinutuzumab (obin) is associated with prolonged survival for patients (pts) with chronic lymphocytic leukemia (CLL, Al Sawaf et al. Blood 2024). We hypothesized that MRD may be used to guide ven tx duration for CLL pts treated with 1L ven + obin. Methods In this ongoing phase II, multicenter investigator-initiated study, pts receive ven + obin for 1L tx of CLL/small lymphocytic lymphoma (NCT04447768). Eligible pts have a CIRS score of ≤ 6 and require 1L tx per iwCLL 2018 criteria. Pts receive 6 x 28-day C of obin and initiate ven on C1D22. Ven duration is dependent on peripheral blood (PB) MRD status measured by ClonoSeq next generation sequencing. At C7, pts undergo MRD testing. Pts uMRD6 (<10-6 sensitivity) at both C7 and C9 dc ven after 9C and enter treatment free observation (TFO). Pts with detectable MRD6 (dMRD6) at C7 undergo repeat testing at C12; if uMRD5 (<10-5) pts dc ven after 12C. Pts dMRD5 at C12 continue ven for an additional 12C (24C total) prior to TFO. The primary study endpoint is 36-month PFS; the unpromising rate is set at 82% and will be tested by a nonparametric survival estimate (Kaplan-Meier) along with Greenwood's formula. RNA sequencing (RNAseq) was performed pre-tx on patient bone marrow (or PB if inaspirable) samples. Unsupervised clustering using machine learning (ML) based on consen...