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High-dose liposomal daunorubicin extended survival in pediatric AML
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First-line treatment with a liposomal formulation of high-dose daunorubicin was associated with longer survival and fewer heart toxicities than standard therapy in children with acute myelogenous leukemia.
“We know that the standard induction treatment regimen is effective in pediatric leukemia patients, but … the toxicities associated with this therapy can be damaging to young patients who are still growing and developing,” Ursula Creutzig, MD, PhD, of the division of pediatric oncology and hematology at Hannover Medical School in Germany, said in a press release. “This unique formulation of daunorubicin might offer us a way to effectively manage AML in these young patients while reducing their risk of experiencing the acute and long-term toxicities associated with traditional regimens.”
Most patients with AML receive first-line chemotherapy with an anthracycline drug. Standard first-line regimens in children include 3 days of an anthracycline and 7 to 10 days of another chemotherapy, such as cytarabine. Approximately 60% to 70% of children with AML achieve long-term survival with this combination, according to background information provided by the researchers.
Previous study findings suggest an increased dose of first-line therapy may be associated with improved remission rates and OS in patients with AML. Yet, clinicians are urged to be cautious about using the increased dose in pediatric patients due to the possible toxicity it poses to their heart muscle.
For this reason, Creutzig and colleagues set out to assess a liposomal formulation of anthracycline daunorubicin (L-DNR; DaunoXome, Galen) in pediatric patients. The investigators hypothesized it would allow for targeted delivery of the drug to cancerous cells while releasing the drug at a decreased pace within the child’s body without the added cardiotoxicity.
Creutzig and colleagues randomly assigned 521 patients aged younger than 18 years to L-DNR (80 mg/m² daily for three days) or idarubicin induction therapy (12 mg/m² daily for three days). Patients in both arms received additional treatment with cytarabine and etoposide.
Patients defined as high risk received additional treatment with a chemotherapeutic agent after induction. Additional maintenance therapy also was administered to all children except those who received a stem cell transplant.
After a median 5 years of follow-up, researchers reported OS of 76% in the L-DNR group and 75% in the idarubicin group.
The probability of EFS was 59% in those assigned L-DNR and 53% in those assigned idarubicin. EFS results were similar among high-risk patients (51% for L-DNR vs. 46% for idarubicin) and standard-risk patients (72% for L-DNR vs. 68% for idarubicin).
Overall, cardiotoxicities were low across both treatment arms, researchers said. Four cases of severe acute cardiotoxicities were reported in the L-DNR arm compared with five cases in the idarubicin arm. During follow-up, one patient assigned L-DNR and three patients assigned idarubicin reported late cardiotoxicities.
Two treatment-associated deaths occurred in the L-DNR group compared with 10 in the idarubicin group.
“These findings signal an important step forward in our goal to identify treatments that can give pediatric patients the best chance for long-term survival with minimal toxic side effects, and we believe the approach could have a number of extended applications,” Creutzig said. “For example, this treatment formulation may be appropriate to use in adults or elderly patients to reduce the toxicity profile, or it may be of value for other malignant diseases in both children and adults. We look forward to further investigating L-DNR as the standard anthracycline induction treatment in future studies.”
Disclosure: One of the researchers reports an advisory board role with Galen.
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