1. Single-center phase 2 study of PD-1 inhibitor combined with DNA hypomethylation agent + CAG regimen in patients with relapsed/refractory acute myeloid leukemia.
- Author
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Gao, Xiao-Ning, Su, Yong-Feng, Li, Meng-yue, Jing, Yu, Wang, Jun, Xu, Lei, Zhang, Lin-Lin, Wang, An, Wang, Yi-Zhi, Zheng, Xuan, Li, Yan-Fen, and Liu, Dai-Hong
- Subjects
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DECITABINE , *ACUTE myeloid leukemia , *DRUG side effects , *PROGRAMMED cell death 1 receptors , *LUNG infections , *DNA , *T cells - Abstract
Anti-PD-1 monotherapy had limited clinical efficacy in relapsed/refractory (r/r) AML patients with higher PD-1 and PD-L1 expression. Hence, we investigated the efficacy and safety of PD-1 inhibitor with DNA hypomethylating agent (HMA) + CAG regimen in patients who had failed prior AML therapy. In this phase 2, single-arm study, r/r AML patients received azacitidine or decitabine plus CAG regimen with tislelizumab. Primary endpoints were efficacy (objective response rate [ORR]) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). Statistical analyses were performed using Stata 14.0 and SPSS 20.0 software where P < 0.05 denoted significance. Twenty-seven patients were enrolled patients and completed 1 cycle, and 14 (51.9%) and 4 (14.8%) patients completed 2 and 3 cycles, respectively. ORR was 63% (14: complete remission [CR]/CR with incomplete hematologic recovery [CRi], 3: partial remission (PR), 10: no response [NR]). Median OS (mOS) and EFS were 9.7 and 9.2 months, respectively. With a median follow-up of 8.2 months (1.1–26.9), the mOS was not reached in responders (CR/CRi/PR) while it was 2.4 months (0.0–5.4) in nonresponders (P = 0.002). Grade 2–3 immune-related adverse events (irAEs) were observed in 4 (14.8%) patients and 3 nonresponders died of lung infection after treatment. Tislelizumab + HMA + CAG regimen showed improved outcomes in r/r AML patients with lower pretherapy leukemia burden. irAEs were mild and low-grade and higher pretherapy bone marrow CD4+ CD127+ PD-1+ T cells might serve as a predictor of treatment response. ClinicalTrials.gov identifier NCT04541277. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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