Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia

Abstract

To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26–80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10−3) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation.

Comparison of Hospital Length of Stay and Supportive Care Utilization Between Patients Treated with CPX-351 and 7+3 for Therapy-Related Acute Myeloid Leukemia or Acute Myeloid Leukemia with Myelodysplasia-Related Changes

“… 35 In a German retrospective, multicenter analysis in patients with newly diagnosed t-AML or AML-MRC, treatment with CPX-351 resulted in a median OS of 21 months. 36 In all 3 studies, CPX-351 was associated with an acceptable safety profile, consistent with results from the phase 3 trial. However, these studies did not address the issue of HRU.…”

New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy

“…In a phase III trial including 309 patients from 60 to 75 years old with ND high-risk AML, CPX-351 showed a significantly improved median OS and higher ORR compared to the classic 7 + 3 approach, despite a longer time to neutrophil and platelet count recovery [ 160 ]. CPX-351 was approved by the FDA and EMA for ND and therapy-related (TR) AML, and real-world data confirmed the efficacy of CPX-351 in monotherapy, with promising outcomes after HSCT [ 161 ].…”

Measurable Residual Disease in High-Risk Acute Myeloid Leukemia

“…Among those 28 responding patients, 16 (57%) achieved MRD negativity (defined as < 10 −3 ), including 8/14 (57%) patients who had available MRD data and proceeded to HCT; so far, OS among transplanted patients was not significantly different between patients with versus without MRD negativity [ 40 ]. In a German retrospective, multicenter analysis in patients with newly diagnosed therapy-related AML or AML-MRC [ 41 ], a total of 36 patients who achieved CR or CRi underwent MRD analysis (by MFC), and 23/36 (64%) achieved MRD negativity (defined as < 10 −3 ); further, all 23 patients proceeded to HCT and continued to exhibit MRD negativity at the time of HCT [ 41 ]. The achievement of MRD negativity was associated with longer OS overall ( p = 0.01) and among patients who proceeded to HCT ( p = 0.02), but not in a multivariable analysis for OS [ 41 ].…”

“…In a German retrospective, multicenter analysis in patients with newly diagnosed therapy-related AML or AML-MRC [ 41 ], a total of 36 patients who achieved CR or CRi underwent MRD analysis (by MFC), and 23/36 (64%) achieved MRD negativity (defined as < 10 −3 ); further, all 23 patients proceeded to HCT and continued to exhibit MRD negativity at the time of HCT [ 41 ]. The achievement of MRD negativity was associated with longer OS overall ( p = 0.01) and among patients who proceeded to HCT ( p = 0.02), but not in a multivariable analysis for OS [ 41 ]. Although these real-world studies found no consistent difference in OS between patients with versus without MRD negativity, it should be noted that their median follow-up times were relatively short (8.6 to 11 months).…”