A phase 2, multicenter, clinical trial of CPX-351 in older patients with secondary or high-risk acute myeloid leukemia: PETHEMA-LAMVYX

Abstract

Background: LAMVYX was a multicenter, single-arm, phase 2 trial designed to validate the safety and efficacy of CPX-351 in patients aged 60-75 years with newly diagnosed, secondary acute myeloid leukemia and to generate evidence on key issues not addressed in the preceding regulatory pivotal trial.

Methods: The primary end point of the study was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate after induction. Eligible patients were recommended to undergo allogeneic hematopoietic stem cell transplantation after the first consolidation cycle. Alternatively, patients could undergo up to six maintenance cycles with CPX-351.

Results: Twenty-nine patients (49%; 95% exact confidence interval [CI], 37%-62%) patients achieved a CR/CRi after one or two cycles of induction, with a measurable residual disease negativity rate of 67% as assessed by centralized, multiparameter flow cytometry. Among patients who had serial next-generation sequencing analyses available, clearance of somatic mutations that were present at diagnosis was achieved in 7 (35%). The median follow-up among survivors was 16.8 months (range, 8.7-24.3 months). The median event-free survival was 3.0 months (95% CI, 1.4-7.3 months), and the median overall survival was 7.4 months (95% CI, 3.7-12.7 months). In landmark analyses at day +100 from diagnosis, the 1-year overall and event-free survival rate among patients who underwent allogeneic hematopoietic stem cell transplantation was 70% (95% CI, 47%-100%) and 70% (95% CI, 47%-100%), respectively. The corresponding values were 89% (95% CI, 71%-100%) and 44% (95% CI, 21%-92%), respectively, for patients who entered the maintenance phase. No significant longitudinal changes were observed in severity index or quality-of-life visual analog scale scores.

Conclusions: The current data provide novel insights that might inform the clinical positioning and optimal use of CPX-351, complementing previous results (ClinicalTrials.gov identifier NCT04230239).

Keywords: acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; maintenance therapy; measurable residual disease; quality of life.

FIGURE 1

Estimates of (A) overall survival, (B) event‐free survival, (C) disease‐free survival, and (D) the cumulative incidence of relapse are illustrated for the entire study cohort.

FIGURE 2

Estimates of overall survival and event‐free survival in patients who (A,B) underwent allogeneic hematopoietic stem cell transplantation or (C,D) entered the maintenance phase. Landmark analyses from day +100 after diagnosis are shown.

FIGURE 3

Estimates of (A) overall survival, and (B) event‐free survival in the propensity score‐matched trial and historical cohorts.

FIGURE 4

Quality‐of‐life analyses as measured by the EQ‐5D‐5L questionnaire. (A) The severity index and (B) EQ‐VAS scores at baseline stratified by early (4‐week) mortality status. (C,D) Longitudinal changes in (C) the severity index and (D) EQ‐VAS scores in responders and nonresponders. Quality‐of‐life metrics were assessed at baseline (time point 1), on day +36 after induction (time point 2), and on day +36 after consolidation cycle 1 (time point 3) and cycle 2 (time point 4). EQ‐5D‐5L indicates the EuroQol 5‐Dimension 5‐Level questionnaire; EQ‐VAS, the EuroQol visual analog scale; n.s., nonsignificant.

FIGURE 5

Mutational clearance assessed by NGS in bone marrow samples in morphologic remission. The number of patients harboring mutations in each gene is shown on top of the corresponding column. NGS indicates next‐generation sequencing; VAF, variant allele frequency.