FDA Approves Daunorubicin/Cytarabine for Pediatric Secondary AML

Kristi Rosa
Kristi Rosa

Managing Editor, OncLive®
Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. She helped launch the rapidly growing infectious disease news resource Contagion, strengthened the Rare Disease Report, of HCPLive, and now serves as the main digital news writer for OncLive. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: krosa@onclive.com

The FDA has approved a revised label for daunorubicin/cytarabine (Vyxeos) to include the treatment of pediatric patients aged 1 year and older with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.

The FDA has approved a revised label for daunorubicin/cytarabine (Vyxeos) to include the treatment of pediatric patients aged 1 year and older with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.1

The approval for the combination for this indication is supported by safety findings from 2 single-arm trials: AAML141 and CPX-MA-201, as well as evidence of efficacy from an acceptable and well-controlled study performed in adults.

"At Jazz Pharmaceuticals, we believe all patients living with complex conditions deserve solutions, and work diligently to expand the science behind our therapies to ensure the greatest number of patients can benefit from our medicines," said Robert Iannone, MD, MSCE, executive vice president, research and development and chief medical officer of Jazz Pharmaceuticals, stated in a press release. "While pediatric patients represent a relatively small percentage of total AML patients, there is a critical need for more effective therapies in this setting. With the expansion of the Vyxeos label to include the pediatric population, Jazz demonstrates our continued commitment to broadening our cancer research and focusing on the people for whom we can have the greatest impact." 

The safety and pharmacokinetics of the regimen in children and young adults were established in 2 clinical trials that enrolled patients with AML or relapsed/refractory hematologic malignancies. The phase 1/2 AAML1421 study enrolled a total of 38 pediatric patients aged 1 to 21 years who had AML in first relapse, while the phase 1 CPX-MA-1201 study enrolled a total of 27 patients aged 1 to 19 years who had relapsed/refractory hematologic malignancies. Results from both efforts revealed no differences in the toxicity profile of the regimen with regard to age.2

Additional data from AAML1421 showed that best responses included 20 complete responses (CR; 54%), 5 CRs with partial recovery of platelet count (CRp; 14%), and 5 CRs with incomplete blood recovery (14%). Moreover, 21 of 25 patients who had CR/CRp were found to have no detectable residual disease (84%).

Furthermore, data from the CPX351-301 study, done in adult patients, provided efficacy evidence to support the decision.

The combination comes with a Boxed Warning stating that it cannot be substituted with other daunorubicin- and/or cytarabine-containing products. In the phase 3 study, the most common toxicities experienced by those who received the regimen included bleeding events, fever, rash, swelling, nausea, sores in the mouth or throat, diarrhea, constipation, muscle pain, and tiredness.3 Other effects reported with the combination included stomach pain, difficulty breathing, headache, cough, decreased appetite, irregular heartbeat, pneumonia, blood infection, chills, sleep disorders and vomiting.

"The expansion of the Vyxeos label to include children is a welcome and necessary advancement in support of some of our most vulnerable patients," said Edward Anders Kolb, MD, director of the Center for Cancer and Blood Disorders at Nemours/Alfred I. DuPont Hospital for Children and chair of myeloid disease committee at Children's Oncology Group, added in the release. "Jazz has been a wonderful partner in pediatric drug development and we are grateful for the continued work being done to provide safe and effective therapies for children."


  1. Jazz Pharmaceuticals announces FDA approval of additional indication for Vyzeos (daunorubicin and cytarabine) for the treatment of secondary acute myeloid leukemia in pediatric patients. News release. Jazz Pharmaceuticals plc. March 30, 2021. Accessed March 30, 2021. https://prn.to/3cxMsIx
  2. Cooper TM, Absalon MJ, Alonzo TA, et al. Phase I/II study of CPX-351 followed by fludarabine, cytarabine, and granulocyte-colony stimulating factor for children with relapsed acute myeloid leukemia: a report from the Children's Oncology Group. J Clin Oncol. 2020;38(19):2170-2177. doi:10.1200/JCO.19.03306
  3. Vyxeos (daunorubicin and cytarabine). Prescribing information. Jazz Pharmaceuticals, Inc. Accessed March 30, 2021.