PF263 DEEP RESPONSE AFTER CPX‐351 TREATMENT IN T‐AML AND MRC‐AML: A REPORT FROM A MULTICENTRIC FRENCH COHORT
Authors: E. Chiche, S. Bertoli, C. Recher, X. Thomas, M. Loschi, C. Bonmati, G. Roth‐Guepin, P. Peterlin, P. Chevallier, C. Lejeune, M. Sauvezie, A. Pigneux, M. Sebert, L. Ades, T. Cluzeau
Journal: HemaSphere (2019)

Background: CPX‐351 is a liposomal formulation of cytarabine and daunorubicin packaged at a 5:1 molar ratio. Recently, drug was approved for patients with therapy‐related acute myeloid leukemia (t‐AML) or AML with myelodysplasia‐related changes (MRC‐AML). Aims: The primary objectives of this study were to analyze efficacy and safety of CPX‐351 in a real‐life setting, including the evaluation of molecular and minimal residual disease (MRD) in responding patients. Methods: We retrospectively collected data from patients treated by CPX‐351 in eight centers in France. Clinical, biological and treatment information were available for all patients. NGS on 19 genes was performed in 29 patients (76%) at diagnosis. Overall response rate (ORR) was defined by complete remission (CR), CR with incomplete hematologic recovery (CRi) and partial remission (PR). MRD by NGS was evaluated for 10 (26%) patients. Overall survival (OS) was calculated from the date of AML diagnosis to the date of death or last follow‐up. All statistical analyses were performed using SPSS v.22 software (IBM SPSS Statistics). Results: Between April 2018 and January 2019, 38 patients treated by CPX‐351 were included in this study. Sex ratio M/F was 20/18 and median age was 66 years (20–83, range). AML subtypes were MRC‐AML (71%) including AML with prior myelodysplastic syndrome (MDS‐AML) (37%), prior chronic myelomonocytic leukemia (CMML‐AML) (8%), or t‐AML (21%). ELN 2017 genetic risk was favorable, intermediate and adverse in 1 (3%), 12 (32%) and 23 (61%) patients, respectively. 42% of patients had complex karyotype, including 75% of monosomal karyotype. NGS analysis revealed mutations in TP53 (n = 8, 21%), TET2 (n = 5, 13%), DNMT3A (n = 4, 11%), ASXL1 (n = 4, 11%), and NPM1 (n = 4, 11%). Three (8%) patients were FLT3‐ITD and 3 (8%) others had FLT3‐TKD. Median time to neutrophil (&gt;0,5 G/L) and platelet (&gt;20 G/L) recovery after induction was 28 (19–73, range) and 30 days (12–76, range), respectively. Only 1 patient discontinued treatment due to grade 3 rash. Twenty‐eight (71%) patients presented at least one grade 3 or more AEs. The most frequent AE was febrile neutropenia in 28 (71%) patients. The other most frequent AEs reported were nausea, mucositis and skin rash in 15 (40%), 7 (18%) and 6 (16%) patients, respectively. Only 2 (5%) patients had an alopecia. Cardiac failure was rare (&lt;3%). ORR was 58% after induction including 47% CR/CRi (CR 42%, CRi 5%) and 11% PR. ORR was also 58% after consolidation but with an increase of patients in CR/CRi (47% and 5%, respectively). 5/10 (50%) patients evaluable for MRD after induction obtained a negative MRD by NGS. Eight (21%) patients underwent an allogeneic hemopoietic stem cell transplant (ASCT). No excess of treatment related mortality was reported in these patients. Median follow up was too short (4 months) to report survival data. Summary/Conclusion: These preliminary data confirmed the efficacy results of the CPX‐351 trial in poor risk AML (t‐AML and MRC‐AML) (Lancet et al., JCO 2018). All investigators reported a favorable safety profile compared to what is known with standard induction chemotherapy. In particular, the frequency of gastro‐intestinal toxicity and alopecia was very low suggesting a better quality of life during induction. Moreover, a substantial number of responding patients achieved negative MRD that may explain the favorable outcome observed after ASCT in the CPX‐351 trial. These results need to be confirmed on a larger cohort.