FDA Approves Combination for Therapy-Related Acute Myeloid Leukemia

The approval covers therapy-related AML and AML with myelodysplasia-related changes

The US Food and Drug Administration (FDA) has approved a fixed combination of daunorubicin and cytarabine (Vyxeos, Jazz Pharmaceuticals) for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia (AML) as well as AML with myelodysplasia-related changes. Patients with either of these types of AML have a very poor prognosis.

“This is the first approved treatment specifically for patients with certain types of high-risk AML,” said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “Vyxeos combines two commonly used chemotherapies into a single formulation that may help some patients live longer than if they were to receive the two therapies separately.”

Therapy-related AML occurs in roughly 8% to 10% of cancer patients treated with radiation or chemotherapy, often within 5 years of treatment. AML with myelodysplasia-related changes is characterized by a history of blood disorders such as myelodysplastic syndromes or myeloproliferative neoplasms as well as other forms of AML with cytogenetic abnormalities or morphologic features.

The approval is based on data from a pivotal phase III trial that compared Vyxeos with cytarabine and daunorubicin (7 + 3) in 309 patients (ages 60 to 75 years) with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. In the Vyxeos arm, patients received induction therapy of 44-mg daunorubicin and 100-mg/m² cytarabine as a fixed combination administered intravenously over a 90-minute infusion on days 1, 3, and 5; and on days 1 and 3 if a second induction was needed. For consolidation, patients received a fixed combination of 29-mg daunorubicin and 65-mg/m² cytarabine on days 1 and 3.

Patients in the 7 + 3 arm received induction therapy of 100-mg/m² cytarabine each day intravenously on days 1–7 by continuous infusion and 60-mg/m² daunorubicin each day on days 1–3. For consolidation, cytarabine was administered on days 1–5 and daunorubicin on days 1 and 2.

The median overall survival was 9.6 months in the Vyxeos arm vs 5.9 months in the 7 + 3 arm (hazard ratio, 0.69; 95% CI 0.52–0.90; P = .005). The complete response rate was also higher in the Vyxeos arm (38% vs 26%; P = .036).

Compared with patients in the 7 + 3 arm, all-cause 30-day mortality was improved in the Vyxeos arm (6% vs 11%), as was all-cause 60-day mortality (14% vs 21%). More patients in the Vyxeos arm were also able to receive hematopoietic stem cell transplant (34% vs 25%).

“Vyxeos is the first chemotherapy to demonstrate an overall survival advantage over the standard of care in a phase III randomized study of older adults with newly-diagnosed therapy-related AML or AML with myelodysplasia-related changes,” said Jeffrey E. Lancet, MD, of the Department of Malignant Hematology at Moffitt Cancer Center, in a press release from Jazz Pharmaceuticals. “The prognosis for these patients is poor, so the FDA approval of this new drug provides a welcome therapeutic advance.”

The most common (occurring in ≥ 25% of patients) adverse events seen in the trial were abdominal pain, arrhythmia, bacteremia, chills, constipation, cough, decreased appetite, diarrhea, dyspnea, edema, headache, hemorrhage, febrile neutropenia, fever, mucositis, musculoskeletal pain, nausea, pneumonia, rash, sleep disorders, and vomiting.

Six percent of patients in each arm of the trial had fatal adverse events on treatment or within 30 days of treatment that was not related to progressive disease. Patients taking Vyxeos should be monitored for decreased cardiac function and hypersensitivity reactions, and Vyxeos has also been associated with serious or fatal bleeding events.

Daunorubicin can leak from the vein or subcutaneous tissue and damage the skin.

Women who are either pregnant or breastfeeding should not take Vyxeos as it may cause harm to the fetus or newborn baby.