New data from a phase 2 trial evaluating CPX-351 in older patients with secondary or high-risk acute myeloid leukemia (AML) provides insights into the drug's efficacy and the complexities of treating this patient population. The study, published in Cancer, suggests that while CPX-351 can be beneficial, several factors influence treatment outcomes, including patient age, disease characteristics, and access to stem cell transplantation.
The multicenter trial, conducted across 12 academic medical centers in Spain, enrolled 59 patients aged 60-75 with newly diagnosed secondary AML (sAML) or high-risk AML. All patients received induction therapy that included granulocyte colony-stimulating factor (G-CSF) priming. The primary endpoint was complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after one or two cycles of induction therapy.
Remission and Survival Rates
The study found that 49% of patients achieved CR or CRi after induction therapy, with a 67% measurable residual disease (MRD) negativity rate. Furthermore, approximately 35% of patients with available data experienced clearance of somatic mutations present at diagnosis. The median event-free survival (EFS) was 3.0 months (95% CI, 1.4-7.3 months), and the median overall survival (OS) was 7.4 months (95% CI, 3.7-12.7 months).
Notably, patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) had higher OS and EFS rates (70% OS [95% CI, 47%-100%] and 70% EFS [95% CI, 47%-100%]).
Comparison to Previous Studies
The researchers, led by Dr. Pau Montesinos from Hospital Universitarii Politècnic La Fe, noted that the CR/CRi rate was similar to that of the pivotal CPX-351 trial, suggesting that G-CSF priming did not significantly impact remission rates. However, the current study had higher early mortality rates and fewer patients underwent allo-HSCT compared to the pivotal phase 3 trial.
"Restrictive protocol recommendations on allo-HSCT indication, with transplantation being advised against in patients older than 70 years (representing 39% of our cohort), the availability of an alternative maintenance option for patients not undergoing allo-HSCT, and the conduct of our trial during the lock-down of the severe acute respiratory virus–coronavirus-2 (SARS–CoV-2) pandemic, might have been contributing factors, all of them potentially influencing the OS results in our study cohort," the authors wrote.
Implications for Treatment Strategies
While the study's EFS and OS rates did not match those seen in some previous real-world studies, the researchers emphasized that their data provide valuable insights into the clinical positioning and optimal use of CPX-351. They also highlighted the unmet need for more effective therapies for certain AML patient subgroups.
"Notwithstanding these limitations, our data provide novel insights that might inform the clinical positioning and optimal use of CPX-351, complementing previous results from pivotal and registry studies," the authors concluded. The study underscores the complexity of treating older patients with secondary or high-risk AML and the importance of considering individual patient characteristics and treatment options, including stem cell transplantation, to optimize outcomes.
