Phase I study of ADI-PEG20 plus low-dose cytarabine for the treatment of acute myeloid leukemia.

Autor: Tsai HJ; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.; Department of Oncology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.; Division of Hematology/Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan., Hsiao HH; Division of Hematology/Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan., Hsu YT; Division of Hematology, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan., Liu YC; Division of Hematology/Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan., Kao HW; Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Linkou, Taiwan., Liu TC; Division of Hematology/Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.; Division of Hematology-Oncology and Cancer Center, Chang Bing Show Chwan Hospital, Changhua, Taiwan., Cho SF; Division of Hematology/Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan., Feng X; Polaris Pharmaceuticals, Inc, Polaris Group, San Diego, CA, USA., Johnston A; Polaris Pharmaceuticals, Inc, Polaris Group, San Diego, CA, USA., Bomalaski JS; Polaris Pharmaceuticals, Inc, Polaris Group, San Diego, CA, USA., Kuo MC; Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Linkou, Taiwan., Chen TY; Division of Hematology, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2021 May; Vol. 10 (9), pp. 2946-2955. Date of Electronic Publication: 2021 Mar 30.
DOI: 10.1002/cam4.3871
Abstrakt: Most acute myeloid leukemia (AML) cells are argininosuccinate synthetase-deficient. Pegylated arginine deiminase (ADI-PEG20) monotherapy depletes circulating arginine, thereby selectively inducing tumor cell death. ADI-PEG20 was shown to induce complete responses in ~10% of relapsed/refractory or poor-risk AML patients. We conducted a phase I, dose-escalation study combining ADI-PEG20 and low-dose cytarabine (LDC) in AML patients. Patients received 20 mg LDC subcutaneously twice daily for 10 days every 28 days and ADI-PEG20 at 18 or 36 mg/m 2 (dose levels 1 and 2) intramuscularly weekly. An expansion cohort for the maximal tolerated dose of ADI-PEG20 was planned to further estimate the toxicity and preliminary response of this regimen. The primary endpoints were safety and tolerability. The secondary endpoints were time on treatment, overall survival (OS), overall response rate (ORR), and biomarkers (pharmacodynamics and immunogenicity detection). Twenty-three patients were included in the study, and seventeen patients were in the expansion cohort (dose level 2). No patients developed dose-limiting toxicities. The most common grade III/IV toxicities were thrombocytopenia (61%), anemia (52%), and neutropenia (30%). One had an allergic reaction to ADI-PEG20. The ORR in 18 evaluable patients was 44.4%, with a median OS of 8.0 (4.5-not reached) months. In seven treatment-naïve patients, the ORR was 71.4% and the complete remission rate was 57.1%. The ADI-PEG20 and LDC combination was well-tolerated and resulted in an encouraging ORR. Further combination studies are warranted. (This trial was registered in ClinicalTrials.gov as a Ph1 Study of ADI-PEG20 Plus Low-Dose Cytarabine in Older Patients With AML, NCT02875093).
(© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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