On August 3, 2017, the U.S. Food and Drug Administration (FDA) approved a new drug for the treatment of poor prognosis (conventional therapy is not effective) acute myeloid leukemia (AML) The new drug, a liposomal combination containing erythromycin and cytarabine (trade name: Vyxeos, manufactured by Jazz Pharmaceuticals), is administered intravenously. This drug is administered intravenously for the treatment of newly diagnosed therapy-related AML (t-AML) and AML with myelodysplasia-related changes (AML-MRC).
Vyxeos is the first drug approved for the treatment of adult patients with t-AML or AML-MRC specifically. Until then, there had been no good treatment options for this type of poor prognosis AML.
What is poor prognosis acute myeloid leukemia?
Acute myeloid leukemia is a rapidly developing cancer in which patients have large numbers of abnormal white blood cells in their blood and bone marrow. Among AMLs, t-AML and AML-MRC are both AMLs with a poor prognosis.
Chemotherapy and radiotherapy are common therapies for cancer. However, clinically, treatment-induced acute myeloid leukemia occurs in 8% to 10% of patients after chemotherapy or radiation therapy, regardless of the primary cancer, and this type of acute myeloid leukemia is called t-AML. t-AML is classified as t-MN (treatment-related myeloid neoplasm) in the 2016 World Health Organization (WHO) classification system, and compared with patients with primary myeloid neoplasm, this category Patients have a significantly shorter survival time.
AML-MRC is also an acute myeloid leukemia with a poor prognosis. According to the 2016 WHO classification system, AML-MRC is usually accompanied by associated cytogenetic abnormalities (both non-equilibrium and equilibrium gene mutations). In the absence of these mutations, AML-MRC can also be diagnosed based on multilineage developmental abnormalities (presence of ≥50% proliferative abnormal cells in at least two or more lineages).
What is Vyxeos?
Vyxeos is a combination of two drugs, erythromycin (daunorubicin) and cytarabine, at a ratio of 44 mg/100 mg. Erythromycin and cytarabine are encapsulated in nanoscale liposomes at a 1:5 molar ratio, and the liposomes not only enhance the efficacy of both chemotherapeutic agents, but also reduce the risk of both drugs.
Rosamycin inhibits DNA and RNA synthesis by inserting between DNA base pairs and by site-blocking. Aglycone acts by inhibiting DNA polymerase and is cell cycle specific for the S phase of cell division. In animal studies, erythromycin and cytarabine were found to have the best synergistic anticancer effect when combined in a 1:5 molar ratio.
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Evidence of efficacy: median overall survival of 9.6 months
The approval of Vyxeos was based primarily on a multicenter randomized controlled trial (CLTR0310-301). A total of 309 patients (60 to 75 years of age) with newly diagnosed t-AML or AML-MRC were enrolled in the study and randomized to Vyxeos treatment or standard chemotherapy, respectively. The standard chemotherapy regimen was erythromycin combined with cytarabine (also known as 7+3) induction chemotherapy, with consolidation chemotherapy, autologous hematopoietic stem cell transplantation (Auto HSCT), and allogeneic hematopoietic stem cell transplantation (Allo-HSCT) available after achieving complete remission.
The results showed that for patients with t-AML or AML-MRC, more patients had consolidation therapy (32% vs 21%) and HSCT (34% vs 25%) after Vyxeos treatment. Moreover, Vyxeos prolonged median overall survival (OS) by 3.7 months compared to standard chemotherapy (9.6 months vs. 5.9 months). The complete remission rate was 38% vs 26%, a statistically significant improvement (P = 0. 036); overall, the 30-day mortality rate was 6% vs 11%.
Black box warning: do not mix with erythromycin or cytarabine
Common adverse reactions to Vyxeos mainly include bleeding, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disturbances, and vomiting.
The FDA states that Vyxeos should not be used in patients with a history of severe allergy to erythromycin, cytarabine, or any component of the formulation. patients should be monitored for allergic reactions and cardiac function when using this drug. vyxeos has been associated with serious or fatal bleeding events. Vyxeos should not be used in women who are pregnant or breastfeeding because of the potential for damage to the developing fetus or newborn.
It is important to note that the instructions for Vyxeos include a black box warning that the drug should never be used interchangeably with erythromycin or cytarabine. are the same, and drug labeling needs to be verified prior to administration.
How do I use Vyxeos?
According to the approved product insert, the recommended use and dosage of Vyxeos is as follows:
- Recommended dose for induction therapy: Vyxeos (erythromycin 44 mg/m and cytarabine 100 mg/m liposome) administered intravenously over >90 minutes on days 1, 3, and 5 of each cycle, and in patients who do not achieve remission in the first cycle, may be re-induced on days 1 and 3 of the second cycle at the re-induction therapy at the same dose on days 1 and 3 of the second cycle in patients who do not achieve remission in the first cycle.
- Recommended dose for consolidation therapy: Vyxeos (erythromycin 29 mg/m and cytarabine 65 mg/m liposome) administered intravenously over >90 minutes on days 1 and 3 of each cycle.
Vyxeo is not yet available in China, but despite its orphan status, the remarkable efficacy of this new immunotoxin is encouraging, and this nanotechnology-encapsulated cytotoxic drug may replace conventional chemotherapy in the future, bringing better efficacy and benefits to patients. This nanotechnology-encapsulated cytotoxic drug may replace traditional chemotherapy in the future, providing better outcomes and less toxic side effects.