Title: Institutional Experience Using CPX-351 in Children with Relapsed/Refractory Myeloid Malignancies

Introduction: Survival rates in pediatric acute myeloid leukemia (AML) are poor, with 40% of patients dying from leukemia or treatment-related toxicity¹. At relapse, AML is rarely curable, with a five-year overall survival (OS) of 30%² despite hematopoietic stem cell transplantation (HSCT). The presence of minimal residual disease (MRD) prior to HSCT is a negative prognostic factor^3,4. Thus, the ability of AML salvage regimens to induce MRD-negative remissions is vital. However, there is no clear consensus regarding the optimal treatment of relapsed/refractory AML. In 2019, the Children’s Oncology Group (COG) released the results of a pediatric phase I/II study (AAML1421) of CPX-351, a liposomal preparation of cytarabine and daunorubicin. This trial of AML in first relapse reported an overall response rate (ORR) of 75.6% after one cycle, similar to other published regimens for relapsed AML with the potential for reduced cardiotoxicity. Based on these results, CPX-351 is often utilized as an AML salvage regimen.

Aim: We present our institutional experience administering CPX-351 to children with relapsed myeloid malignancies to provide a “real-world” experience that more closely recapitulates the heterogeneity of relapsed disease.

Method: We performed a retrospective chart review at UCSF Benioff Children’s Hospitals from January 2016 through August 2023 after institutional review board approval. We identified all patients who received CPX-351 as a salvage regimen for relapsed myeloid malignancies, including those who received CPX-351 with other targeted agents.

Results: We identified a diverse group of 11 patients with relapsed AML (n=5), myeloid neoplasm post-cytotoxic therapy (MN-pCT, formerly known as treatment-related AML) (n=3), treatment-related mixed phenotype acute leukemia (t-MPAL) (n=1), B/Myeloid MPAL (n=1) , and myelodysplasia-related AML (AML-MR) (n=1). This cohort of patients was similar in age, CNS status, and prior HSCT status to the AAML1421 cohort. While we observed a 100% ORR, only 2/11 (18%) achieved MRD negativity and OS was dismal at 18%.

Discussion: In this heterogeneous “real world” cohort of patients with relapsed/refractory pediatric myeloid malignancies, CPX-351 was associated with a very low frequency of

MRD-negative remissions and similarly discouraging OS. Acknowledging the critical limitations of small sample size and disease heterogeneity, based on our findings, CPX-351 does not appear superior to other regimens, particularly those containing venetoclax (33-48% MRD negativity rate)^5,6. Further study on a larger scale and novel, targeted agents are needed to improve survival of children with relapsed and refractory myeloid malignancies.