威尼斯人
伊布替尼
医学
内科学
中性粒细胞减少症
肿瘤科
胃肠病学
作者
Lydia Scarfo,Silvia Heltai,Elisa Albi,Eloise Scarano,Luana Schiattone,Lucia Farina,Riccardo Moia,Marina Deodato,Andrea Ferrario,Marina Motta,Gianluigi Reda,Rosaria Sancetta,Marta Coscia,Paolo Rivela,Luca Laurenti,Marzia Varettoni,Eleonora Perotta,Antonella Capasso,Pamela Ranghetti,Maria Colia,Paolo Ghia
出处
期刊:Blood
[American Society of Hematology]
日期:2022-08-03
标识
DOI:10.1182/blood.2022016901
摘要
Undetectable MRD (uMRD) is achievable in patients with CLL with the BCL2-inhibitor venetoclax alone or combined with the BTK-inhibitor ibrutinib. This phase 2 multicenter MRD-driven study was designed to discontinue treatment upon reaching uMRD4(<10-4) in patients with relapsed/refractory CLL receiving venetoclax monotherapy or after the addition of ibrutinib. Primary endpoint of the study was proportion of uMRD4 with venetoclax+/-ibrutinib. Secondary endpoints were ORR, PR, CR, PFS, DOR, OS, and safety of venetoclax+/-ibrutinib. Patients with uMRD4 at Cycle12Day1 discontinued venetoclax. MRD+ patients added ibrutinib and continued both drugs up to Cycle24Day28/uMRD4/progression/toxicity. After Cycle24Day28, MRD+ patients continued ibrutinib. Thirty-eight patients (29% with TP53-aberrations; 79% unmutated IGHV) started venetoclax. ORR with venetoclax was 36/38(95%) (20 complete; 16 partial response). Seventeen patients (45%) with uMRD4 at Cycle12Day1 discontinued venetoclax. Nineteen (55%) MRD+ subjects added ibrutinib. After a median of 7 months (range 3-10) of combined treatment, 16/19 (84%) achieved uMRD4, thus stopping both drugs. Two MRD+ patients at Cycle 24 Day 28 continued ibrutinib until progression/toxicity. After a median follow-up of 36.5 months, median PFS was not reached; 10 patients progressed (4 restarted venetoclax, 3 without treatment need, 2 developed Richter transformation, 1 dropped-out). 7/32 patients (22%) remain uMRD4 after 3 years of follow-up. Neutropenia was the most frequent G3-4 adverse event, no grade 5 events occurred on study. This sequential MRD-guided approach led to uMRD4 in 33/38 patients (87%) with venetoclax monotherapy or combined with ibrutinib., delivering treatment combination only in a fraction, and ultimately identifying the few patients benefiting from continuous therapy. Clinical trial number: NCT04754035
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