Clinical Perspectives


Genetic Subtypes of AML Being Explored for Response to CPX-351

December 07, 2019

CPX 351 890X510

Watch Dr. Jeff Lancet highlight outcomes in patients with therapy-related AML who achieved remission with CPX351 versus 7+3.


At the 2019 American Society of Hematology conference, Dr. Jeffrey E. Lancet, Malignant Hematology Chair and chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center, followed up impactful research on the liposomal formulation, CPX-351. The phase 3 study's findings report that in older patients with newly diagnosed, high-risk/secondary AML, CPX-351 significantly improved overall survival versus conventional 7+3, with a comparable safety profile. 

"Similar to what we saw in the overall population of patients on the phase 3 study, the therapy-related-AML patients also had a longer survival after transplant than the 7+3 patients," said Dr. Lancet. "Certainly the data that we've seen across survival, success after transplant, and remission rates are very similar to the overall population of patients suggesting that this high-risk group of patients is experiencing some benefit from CPX-351."

Dr. Jeffrey Lancet, Chair, Department of Malignant Hematology

CPX-351 (Vyxeos) contains a fixed combination of cytarabine and daunorubicin in a 5:1 molar ratio. After showing earlier significantly improved overall survival, event-free survival, and response rates in comparison with the standard regimen of cytarabine and daunorubicin (7+3), CPX-351 is considered as the standard for first-line treatment of older patients with high-risk or secondary AML who are fit for intensive chemotherapy.

In this study, among therapy-related-AML patients who achieved a complete remission + complete remission with incomplete hematologic recovery, CPX-351 improved median overall survival versus 7+3 chemotherapy. Differences in outcomes may have been influenced by fewer patients treated with 7+3 who received prior radiation therapy only. The safety profile for CPX-351 in this subgroup was generally consistent with the known profile of 7+3.

TP53 mutations were associated with a poor prognosis, irrespective of treatment arm, whereas median overall survival (OS) was longer with CPX-351 compared with 7+3 among patients with two of the most common mutations, DNMT3A and TET2. Exploratory analyses of baseline and post-treatment molecular (mutational) characteristics is ongoing.

"The baseline molecular status was explored to see what genetic subtypes may respond favorably to CPX-351. We have learned that a better OS was associated in a variety of mutational sub-sets." Dr. Lancet said, "The TP53 mutated subgroup did not benefit from CPX-351, confirming the need to target this particular mutant protein with other novel therapies. We hope to gain more knowledge and more data with real-world setting analysis to be able to update these results and expand as we treat more patients with this very difficult sub-type in the future."