Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004

Abstract

Key Points• AML induction with liposomal daunorubicin (80 mg/m 2 per day for 3 days) shows antileukemic activity comparable to idarubicin (12 mg/m 2 per day for 3 days).• Liposomal daunorubicin promises to be more active in the t(8;21) subgroup and causes less treatment-related toxicity.Outcomes of patients with acute myeloid leukemia (AML) improve significantly by intensification of induction. To further intensify anthracycline dosage without increasing cardiotoxicity, we compared potentially less cardiotoxic liposomal daunorubicin (L-DNR) to idarubicin at a higher-than-equivalent dose (80 vs 12 mg/m 2 per day for 3 days) during induction. In the multicenter therapy-optimization trial AML-BFM 2004, 521 of 611 pediatric patients (85%) were randomly assigned to L-DNR or idarubicin induction. Five-year results in both treatment arms were similar (overall survival 76% 6 3% [L-DNR] vs 75% 6 3% [idarubicin], P logrank 5 .65; event-free survival [EFS] 59% 6 3% vs 53% 6 3%, P logrank 5 .25; cumulative incidence of relapse 29% 6 3% vs 31% 6 3%, P (Gray) 5 .75), as were EFS results for standard (72% 6 5% vs 68% 6 5%, P logrank 5 .47) and high-risk (51% 6 4% vs 46% 6 4%, P logrank 5 .45) patients. L-DNR resulted in significantly better probability of EFS in patients with t(8;21). Overall, treatment-related mortality was lower with L-DNR than idarubicin (2/257 vs 10/264 patients, P 5 .04). Grade 3/4 cardiotoxicity was rare after induction (4 L-DNR vs 5 idarubicin). Only 1 L-DNR and 3 idarubicin patients presented with subclinical or mild cardiomyopathy during follow-up. In conclusion, at the given dose, L-DNR has overall antileukemic activity comparable to idarubicin, promises to be more active in subgroups, and causes less treatment-related mortality. This trial was registered at www.clinicaltrials.gov as #NCT00111345. (Blood. 2013;122(1):37-43)

Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial

“…33 Two patients died due to cardiac failure, underscoring the sensitivity of children with DS to cardiotoxic agents. Thus, lowering cardiotoxicity, for example, by introducing liposomal formulations of daunorubicin, 34 should be an aim for the development of future treatment protocols.…”

Pediatric acute myeloid leukemia with t(8;21) variant: what is the value on clinical outcome?

“…15 After the diagnosis, the patient was subjected to chemotherapy, complying with the Berlin-FrankfurtMünster Protocol (BFM-2004). 16 In accordance with this protocol, being an AML-M2 with absence of Auer rods, DCS patient was stratified as high risk with indication for transplantation. After complete remission, the patient continued on maintenance therapy until submitted to related allogeneic BM transplant, in December 2011.…”

Modern strategies in AML treatment

“…Большинство ле-чебных мероприятий были признаны безопасными, почти все рандомизированные клинические исследо-вания показали сравнимые результаты между отдель-ными терапевтическими группами. Например, в иссле-довании группы BFM (Berlin-Frankfurt-Münster Group) пациенты с ОМЛ (n = 521) были рандомизиро-ваны для получения липосомального даунорубицина (80 мг/м 2 /сут в течение 3 дней) или идаруцибина (12 мг/м 2 /сут в течение 3 дней) в сочетании с цитара-бином и этопозидом в индукционной терапии в рамках протокола AML-BFM-2004 [2]. Хотя были получены чрезвычайно хорошие результаты, не было никаких различий в выживаемости между пациентами, прини-мающими липосомальный даунорубицин (76 %) и ида-руцибин (75 %).…”