No Loss of Efficacy with Anthracycline-Free Induction for Acute Lymphoblastic Leukemia

Charles Bankhead

May 2013, Vol 4, No 4 - Hematologic Malignancies

Children with acute lymphoblastic leukemia (ALL) had no drop-off in efficacy with an anthracycline-free regimen that also reduced the long-term risk of cardiotoxicity, reported Andre Baruchel, MD, PhD, Chief of Pediatric Hematology, Robert Debré University Hospital, Paris, France.

Induction therapy without daunorubicin (Cerubidine) led to a 5-year event-free survival (EFS) rate of almost 97%, slightly better than the rate observed in children who received conventional induction that included the anthracycline agent.

“The patients had excellent survival with or without daunorubicin,” Dr Baruchel said. “We now have strong evidence that reducing the amount of chemotherapy initially administered to these children does not negatively affect their immediate outcome.”

“Perhaps more important, we now know that eliminating harmful chemotherapy from their treatment can help minimize their risk of experiencing heart damage later in life. Anthra­cyclines have an unclear benefit on efficacy but a clear risk of additive toxicity.”

A recent Cochrane Review of therapy for ALL included only 3 publications involving anthracycline-containing regimens, which were all published more than 20 years ago.

The results provide high-quality clinical trial results to support a practice that has become commonplace in the United States, said William G. Woods, MD, who heads the Aflac Cancer and Blood Disorders Center at Children’s Healthcare in Atlanta, GA. Studies conducted in the United States in the 1980s and 1990s demonstrated the nonessential contributions of low-dose anthracyclines in induction therapy for ALL.

Low-dose anthracyclines continue to be used in consolidation and maintenance therapy.

“The hope is that we will be able to eliminate anthracyclines by substitution of other drugs, especially novel drugs,” noted Dr Woods.

Dr Baruchel presented the results from a randomized clinical trial of 1128 patients with newly diagnosed ALL. Each patient received a standard induction regimen that included vincristine (Oncovin), dexamethasone (Decadron), and asparaginase (Elspar). The patients were randomized to daunorubicin or to no additional induction therapy. The primary end point was EFS.

On completion of induction therapy, the rates of minimal residual disease (MRD) ≥1% were 1.8% among patients who received the anthracycline and 1.9% with those who were treated with the anthracycline-free regimen. De­fining MRD as ≥0.1% resulted in rates of 6.5% for the daunorubicin group and of 9.3% for the patients who received the anthracycline-free regimen.

After a median follow-up of 69 months, the overall survival rate was 97% in the entire study population. The 5-year EFS rate was 95.4% with daunorubicin induction and 96.8% with the anthracycline-free regimen.

Dr Baruchel emphasized that omission of daunorubicin pertained only to patients with standard-risk ALL that demonstrates a good early response to the other 3 drugs in the induction regimen.