Single Cycle of Arsenic Trioxide–Based Consolidation Chemotherapy Spares Anthracycline Exposure in the Primary Management of Acute Promyelocytic Leukemia

Abstract

A B S T R A C T PurposeEvent-free survival following all-trans-retinoic acid (ATRA) -based therapy for acute promyelocytic leukemia (APL) averages 70% at 5 years. While arsenic trioxide (ATO) can induce remissions in 95% of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents. Patients and MethodsAfter induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy. ResultsForty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90%; overall survival for all patients was 88%. Despite a total anthracycline dose of only 360 mg/m 2 , cardiac ejection fraction decreased by Ն 20% in 20% of patients. ConclusionThese data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.

All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4)

“…In a similar ATRA and chemotherapy protocol, postinduction ATO has been used as a substitute for the second cycle of consolidation chemotherapy. 25 The Shanghai 11 and Changsha 26 groups have also demonstrated excellent outcomes with ATRA-and ATO-based induction therapy, although both studies variably used additional cytotoxic agents during induction for high-risk patients. In addition, both studies used substantial postremission chemotherapy (daunorubicin, cytarabine, and homoharringtonine) in multiple cycles of consolidation (Table 6).…”

“…Although the median followup in this interim analysis is relatively short, it is comparable with several other studies with a median followup that was less than 3 years at the time of reporting. 3,12,13,22,25,26 Nevertheless, we recognize that additional relapses are likely to be seen with a longer period of observation, and a final APML4 analysis will be performed when the last registered patient has been followed for a minimum of 2 years after consolidation. The strategy that most closely resembles APML4 was reported by investigators at the MD Anderson Cancer Center.…”

Arsenic trioxide in acute promyelocytic leukemia: potion not poison

“…In a smaller Phase II trial similar outcomes have been described using a single course of consolidation therapy using cytarabine followed by 30 doses of ATO [20].…”

A Canadian Consensus on the Management of Newly Diagnosed and Relapsed Acute Promyelocytic Leukemia in Adults

“…Induction therapy using such a regimen yields a complete response (cr) rate in the 90%-95% range 3 . The role of ato became clearer after several studies showed efficacy and safety for ato with or without atra in the relapsed setting 22,23 and, more recently, in first-line induction and consolidation 6,7,[24][25][26] . In 1998, Soignet et al 22 were the first to corroborate reports from China about the efficacy of ato in treating apl by showing that ato is highly efficacious at inducing remission in relapsed disease.…”

“…Rates of cr ranged from 84.7% to 97%, and rates of disease-free survival ranged from 72% (median follow-up: 16.5 months) to 97.4% at 5 years 7,24,25,[31][32][33][34][35][36] . The os rates ranged from 86% at 3 years to 91.7% at 5 years 7,24,25,[31][32][33][34][35][36] . One study that combined ato, atra, and idarubicin in induction and ato and atra in consolidation demonstrated equally favourable outcomes in 2-year os rates, regardless of Sanz risk category 7 .…”