**Conflict of interest**

*Acute Leukemias*

CPX-351 [19].

**6. Conclusion**

using either daunorubicin 90 mg/m2

the evidence presented above.

rior to daunorubicin 45 mg/m2

replace daunorubicin 90 mg/m2

daunorubicin 45 mg/m2

When choosing between 45 mg/m2

leukemia cells [43, 44].

is observed, leading to prolonged myelosuppression, in addition to apoptosis of

approved for the treatment of adults with therapy related AML or AML with myelodysplasia-related changes. A phase III study compared cytarabine + liposo-

patients (60–75 years) with secondary AML. The study enrolled 309 patients. CPX-351 was associated with a higher remission rate (47.7% vs. 33.3%, p = 0.016) as well as improved median overall survival (9.6 m vs. 5.9 m, HR 0.69, p = 0.003) compared to 7 + 3. There was no difference in early mortality between the two treatments. Prolonged neutropenia and thrombocytopenia were observed with

Although the study above was limited to older patients, the FDA approved CPX-351 for all adults. The reason being that therapy related AML or AML with myelodysplasia-related changes are thought to be biologically aggressive subtypes, regardless of age. Whether CPX-351 is superior, in patients <60 years old, to 7 + 3

ongoing studies in younger patients as well as planned clinical trials using CPX-351 in combination with targeted therapy or immunotherapy should help identify

AML is a heterogenous disease and the treatment plan for every patient is different. Both patient and disease related variables help determine the appropriate treatment option for each case. It is challenging to state the outright superiority of one anthracycline over another, but some useful conclusions can be drawn from

, 60 mg/m<sup>2</sup>

it is reasonable to look at patient age and cytogenetic and molecular abnormalities (if available in a timely manner), before picking one. Daunorubicin 45 mg/m<sup>2</sup> should be used for older patients >65 years of age based on the available evidence.

but unfortunately there is lack of randomized data to support one dose over the other. For patients younger than 65 years of age, daunorubicin 90 mg/m2

and DNMT3A-mutant AML seem to derive benefit from daunorubicin 90 mg/m2

patients. It also appears to be as safe and effective as daunorubicin 90 mg/m<sup>2</sup>

, may still be the first choice. Mitoxantrone is comparable to both idarubicin and daunorubicin. It's use in upfront therapy is still not as common as the other 2 available agents. CPX-351

One caveat to the idarubicin vs. high dose daunorubicin studies is the small representation of older patients (>65 years). For older patients fit for intensive therapy,

Whereas novel drug regimens are emerging in the treatment of AML, intensive chemotherapy still plays a significant role. Anthracyclines will serve as the backbone of AML treatment in fit patients and therefore it is important to know which

additional subsets of patients that may derive benefit from this drug.

It is probably safe and effective to use daunorubicin 60 mg/m2

However, data is emerging to suggest that daunorubicin 60 mg/m2

.

Idarubicin is superior to daunorubicin 45 mg/m2

for FLT3-mutant AML where daunorubicin 90 mg/m<sup>2</sup>

should be the first choice in patients with secondary AML.

type and dose to select in the appropriate setting.

mal daunorubicin (CPX-351, Vyxeos) to 7 + 3 (daunorubicin 60 mg/m<sup>2</sup>

:100 mg/m<sup>2</sup>

or idarubicin is not known. The results of

and 90 mg/m<sup>2</sup>

. All cytogenetic risk categories and FLT3, NPM1

of daunorubicin,

is supe-

can effectively

, when used as 7 + 3, in younger

may have a slight advantage.

.

, except

in this age group,

is FDA

), in older

The liposome of daunorubin:cytarabine 44 mg/m<sup>2</sup>

**160**

The authors declare no conflict of interest.
