TY - JOUR
T1 - All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4)
AU - Iland, Harry J.
AU - Bradstock, Ken
AU - Supple, Shane G.
AU - Catalano, Alberto
AU - Collins, Marnie
AU - Hertzberg, Mark
AU - Browett, Peter
AU - Grigg, Andrew
AU - Firkin, Frank
AU - Hugman, Amanda
AU - Reynolds, John
AU - Di Iulio, Juliana
AU - Tiley, Campbell
AU - Taylor, Kerry
AU - Filshie, Robin
AU - Seldon, Michael
AU - Taper, John
AU - Szer, Jeff
AU - Moore, John
AU - Bashford, John
AU - Seymour, John F.
AU - for the Australasian Leukaemia and Lymphoma Group
PY - 2012/8/23
Y1 - 2012/8/23
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84865427746
U2 - 10.1182/blood-2012-02-410746
DO - 10.1182/blood-2012-02-410746
M3 - Article
C2 - 22715121
AN - SCOPUS:84865427746
SN - 0006-4971
VL - 120
SP - 1570
EP - 1580
JO - Blood
JF - Blood
IS - 8
ER -