Yi Miao, Ming Liu, Shuchao Qin, Fei Li, Jin Zhang, Hongling Peng, Chunyan Ji, Luomengjia Dai, Ziyuan Zhou, Chongyang Ding, Zhen Wang, Yeqin Sha, Tonglu Qiu, Hanning Tang, Hui Jin, Lei Fan, Wei Xu, Jianyong Li, Yi Xia, Huayuan Zhu
The study meet the primary endpoint, showing the potential efficacy and acceptable safety profile of the OFCG regimen as a first-line treatment for CLL. Trial registration: NCT05322733.
BACKGROUND: This multicenter phase II trial aimed to evaluate the orelabrutinib, fludarabine, cyclophosphamide, and obinutuzumab (OFCG) regimen as first-line therapy for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma without restriction by TP53 aberrations [del(17p) and/or TP53 mutation] and IGHV status.
METHODS: Eligible patients received OFCG (orelabrutinib, orally 150 mg/day; fludarabine, intravenously 25 mg/m2/day; cyclophosphamide, intravenously 250 mg/m2/day; obinutuzumab, intravenously 1000 mg), with treatment duration and modifications based on prespecified minimal residual disease (MRD) criteria. The primary endpoint was the rate of undetectable MRD in bone marrow (BM-uMRD) after 6 cycles by flow cytometry (10-4 sensitivity). The key secondary endpoints included the rate of BM-uMRD4 at the end of cycles 3, 12, MRD in peripheral blood (PB-uMRD4) at the end of cycles 6, and complete response rate (CRR); exploratory endpoints included the rate of BM-uMRD6 (10-6 sensitivity) at the end of cycles 3, 6, and 12.
RESULTS: Among 25 enrolled patients, 23 completed 3 cycles of OFCG therapy; of these, 13 patients achieved BM-uMRD4. After 6 cycles, 76.0 % (19/25) achieved BM-uMRD4, and 80 % (20/25) of patients achieved PB-uMRD4. CRR with BM-uMRD4 was achieved by 20.0 % (5/25), 52.0 % (13/25), and 64.0 % (16/25) of patients after 3, 6, and 12 cycles, respectively. Significant differences in BM-uMRD6 at C7D0 (odds ratio [OR], 0.03 [95 % confidence interval [CI]: 0, 0.32]; P < 0.01) and C13D0 (OR, 0.16 [95 % CI: 0.03, 0.94]; P < 0.05) were observed between IGHV-mutated (n = 10) and unmutated (n = 15) patients. Notably, 20 patients discontinued all the drugs at the data cutoff date. No treatment-related deaths occurred, and the most frequent grade 3-4 adverse effects (AEs) were neutropenia (20/25, 80.0 %), thrombocytopenia (15/25, 60.0 %), and infection (7/25, 28.0 %).
CONCLUSION: The study meet the primary endpoint, showing the potential efficacy and acceptable safety profile of the OFCG regimen as a first-line treatment for CLL. Trial registration: NCT05322733.