Findings from a Phase 3 acute myeloid leukemia trial presented at #ASH24 show CPX-351 improves survival for AML-MR patients. Lead authors Shai Shimony, MD, MPH, and H. Moses Murdoch, MD, of Dana-Farber Cancer Institute, explain more in this video.
So older patients who develop acute myeloid leukemia or AML after treatment for another cancer or a prior MDS, which is a more chronic blood cancer, have very aggressive disease with poor outcomes. In this high risk group of patients, CPX 351, which is a liposomal formulation of cytarabine and an anthrocycline, was shown to improve survival compared to traditional chemotherapy in a phase 3 trial and gained FDA approval. However, as a field, our understanding of AML continues to grow, and as a result, our diagnostic and prognostic categories are now defined based on the presence of mutations identified at diagnosis. Rather than that clinical history, because of this, it is now unclear which patients benefit from CPX 351 when considering modern genetic categories of AML. And so to clarify this question, we performed a genetic reanalysis of the pivotal randomized phase 3 trial of CPX 351 versus 7 + 3 chemotherapy. We reclassified the 184 patients for whom we had genetic information into 4 categories. Those with T53 mutations, those with mutations in genes associated with prior MDS, known as AMLMR, patients with mutations in the gene DDX41, and all other patients were categorized in the de novo genetic group. We found that the benefit of CIBIC 351/7 + 3 was restricted to patients in the AMR group only, with no difference in survival between treatment groups for those with T53, DH 41, or the novo mutations. TP53 AML is a very challenging to treat leukemia, and we found that allelic status rather than treatment was associated with survival. Within the AMLMR group, we found that the benefit of CPX 351 was related to improved survival among those who underwent allogeneic hematopaic stem cell transplantation. The recovery of blood counts was longer in patients treated with CPX 351, regardless of the genetic group. Our study suggests that patients in the AMLMR group should be treated with CPX 351/7 + 3 and questions the role of CPX 351 in TP53 mutated AML.
