Initial results of a multicenter phase 2 study of venetoclax in combination with R‐CHOP (VR‐CHOP) for patients with Richter Syndrome

作者：Matthew Steven Davids, Kathleen A. Rogers, Nitin Jain, Svitlana Tyekucheva, Yi Lin Ren, Chris Carey, Josie S. Montegaard, Michelle Hajdenberg, Christine E. Ryan, R. Merryman, Alexander V. Kim, Jennifer Leigh Crombie, Caron Alyce Jacobson, Ann Steward LaCasce, David Christopher Fisher, Inhye E. Ahn, Erin Michelle Parry, Jennifer R. Brown, Philip A. Thompson · 发表于：Hematological Oncology · 年份：2023 · DOI：10.1002/hon.3164_343 · 被引用次数：24 · 研究领域：Chronic Lymphocytic Leukemia Research、Calcium signaling and nucleotide metabolism、PI3K/AKT/mTOR signaling in cancer

Introduction: We previously reported promising efficacy for venetoclax (V) plus da-R-EPOCH (VR-EPOCH) for 26 patients (pts) with CLL who developed Richter Syndrome (RS), with a CR rate of 50% and median OS of 19.6 mo.; however, hematologic and infectious complications were common (Davids et al., Blood, 2022). We hypothesized that de-intensifying the chemoimmunotherapy backbone while keeping the venetoclax could potentially preserve efficacy while mitigating the toxicities observed with this approach. Here, we report for the first time on an ongoing study of VR-CHOP in RS. Methods: This is a single-arm, phase 2, investigator sponsored trial of VR-CHOP for RS (NCT03054896) open at 3 US sites. We treated pts with CLL and biopsy-confirmed DLBCL with R-CHOP for 1 cycle, then after count recovery with accelerated inpatient daily V ramp-up (20/50/100/200/400 mg), then VR-CHOP outpatient for up to 5 additional 21d cycles (V 400 mg qd, d1–10 of each cycle) with mandatory G-CSF support. Responders could then receive daily V 400 mg qd maintenance in 28d cycles or elect to come off study for alloHCT. Response was by Lugano criteria with PET/CT, toxicity by CTCAE v4.03. Results: As of 24 Feb 2023, 27 pts have started study treatment. Median age: 72 yrs (range 42–80), 37% had del(17p) or TP53 mut, 26% had NOTCH1 mut. Median # prior CLL treatments was 1 (range 1–9), including 44% post-BTKi and 17% post-V; 4 pts (15%) had prior treatment for RS. Median # of VR-CHOP cycles to date in this ong...