Comparing Outcomes Between CPX‐351 and Fludarabine‐Based Induction in Secondary Acute Myeloid Leukemia in the Real‐World Setting: The Prognostic Role of Measurable Residual Disease

ABSTRACT Secondary acute myeloid leukemia (s‐AML) is associated with inferior outcomes with conventional chemotherapy, and fludarabine combinations (FLAG‐Ida) have been tested to improve results. More recently, CPX‐351 resulted superior to conventional 3 + 7 in s‐AML patients. In the UK NCRI AML19 trial, AML patients were randomized to receive either FLAG‐Ida or CPX‐351. Subgroup analysis revealed better overall survival (OS) with CPX‐351 in patients with MDS‐related gene mutations. Unfortunately, minimal residual disease (MRD) was evaluated only in a minority of patients. The aim of this study was to further disclose the mechanisms of higher efficacy of CPX‐351 in s‐AML, with a focus on MRD. We analyzed 183 consecutive s‐AML elderly patients (median age 69, range 60–77) treated with CPX‐351 ( n = 82) or receiving FLAG‐Ida ( n = 101). Complete remission (CR) rate and MRD negativity probability were higher among patients receiving CPX‐351 (MRD negative CR rate of 40/64, 62.5%, compared to 25/55, 45% in patients who received FLAG‐Ida, p < 0.05). Extra‐hematological toxicity was lower in CPX‐351 arm, and 30 days mortality was 3.6% and 8% in patients receiving CPX‐351 or FLAG‐Ida, respectively. Notably, 21/64 (32.8%) CR patients treated with CPX 351 underwent allogeneic stem cell transplantation (HSCT), compared to 5/55 with FLAG‐Ida (9%, p < 0.05). Overall, CPX‐351 treatment resulted in higher OS (median OS 17.7 vs. 11.2 months with FLAG‐Ida, p < 0.05). The better outcome of CPX‐351 compared to FLAG‐Ida in our cohort may be explained by a greater probability of MRD negativity, alongside with an improved tolerance, enabling more s‐AML patients to undergo HSCT.