Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation.

Autor: Gill H; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China., Yim R; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China., Pang HH; School of Public Health, The University of Hong Kong, Hong Kong SAR, China., Lee P; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China., Chan TSY; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China., Hwang YY; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China., Leung GMK; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China., Ip HW; Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China., Leung RYY; Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China., Yip SF; Department of Medicine, Tuen Mun Hospital, Hong Kong SAR, China., Kho B; Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China., Lee HKK; Department of Medicine, Princess Margaret Hospital, Hong Kong SAR, China., Mak V; Department of Medicine, Princess Margaret Hospital, Hong Kong SAR, China., Chan CC; Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China., Lau JSM; Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China., Lau CK; Department of Medicine, Tseung Kwan O Hospital, Hong Kong SAR, China., Lin SY; Department of Medicine, United Christian Hospital, Hong Kong SAR, China., Wong RSM; Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China., Li W; Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong SAR, China., Ma ESK; Department of Pathology, Hong Kong Sanatorium and Hospital, Hong Kong SAR, China., Li J; Department of Infectious Diseases and Public Health, The City University of Hong Kong, Hong Kong SAR, China.; School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, China., Panagiotou G; School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, China.; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.; Department of Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany., Sim JPY; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China., Lie AKW; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China., Kwong YL; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2020 May; Vol. 9 (10), pp. 3371-3382. Date of Electronic Publication: 2020 Mar 18.
DOI: 10.1002/cam4.2865
Abstrakt: Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18- to 65-year-old AML patients refractory to first-line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high-dose cytarabine consolidation, with clofarabine (30 mg/m 2 /d, Days 1-5), cytarabine (750 mg/m 2 /d, Days 1-5), and mitoxantrone (12 mg/m 2 /d, Days 3-5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mutational profile of a 69-gene panel was evaluated. Twenty-six men and 26 women at a median age of 46 (22-65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty-two CR/CRi patients underwent allo-HSCT. The 2-year overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo-HSCT (P = .005), and superior RFS and EFS were associated with allo-HSCT (P < .001). Remarkably, CR after CLAM and allo-HSCT resulted in 2-year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment-related mortality and the performance of allo-HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).
(© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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