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All-trans-retinoic Acid, Idarubicin, and IV Arsenic Trioxide as Initial Therapy in Acute Promyelocytic Leukemia (APML4)

All-trans-retinoic Acid, Idarubicin, and IV Arsenic Trioxide as Initial Therapy in Acute Promyelocytic Leukemia (APML4)

Harry J Iland, Ken Bradstock, Shane G Supple, Alberto Catalano, Marnie Collins, Mark Hertzberg, Peter Browett, Andrew Grigg, Frank Firkin, Amanda Hugman, John Reynolds, Juliana Di Iulio, Campbell Tiley, etc.

Blood. 2012 Aug 23;120(8):1570-80; quiz 1752.

PMID: 22715121

Abstract:

The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of all-trans-retinoic acid (ATRA), anthracycline-based chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome. Consolidation comprised 2 cycles of ATRA and ATO without chemotherapy, followed by 2 years of maintenance with ATRA, oral methotrexate, and 6-mercaptopurine. Of 124 evaluable patients, there were 4 (3.2%) early deaths, 118 (95%) hematologic complete remissions, and all 112 patients who commenced consolidation attained molecular complete remission. The 2-year rate for freedom from relapse is 97.5%, failure-free survival 88.1%, and overall survival 93.2%. These outcomes were not influenced by FLT3 mutation status, whereas failure-free survival was correlated with Sanz risk stratification (P[trend] = .03). Compared with our previously reported ATRA/idarubicin-based protocol (APML3), APML4 patients had statistically significantly improved freedom from relapse (P = .006) and failure-free survival (P = .01). In conclusion, the use of ATO in both induction and consolidation achieved excellent outcomes despite a substantial reduction in anthracycline exposure. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12605000070639.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP57852570-A	Idarubicin		57852-57-0	Price

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