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7042 Background: CPX-351, a liposomal encapsulation of cytarabine (C) and daunorubicin (D) at a synergistic ratio, is approved as Vyxeos in the US and EU for adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. In a phase 3 study, CPX-351 significantly improved OS and remission rates vs 7+3 in patients (pts) aged 60-75 y with newly diagnosed high-risk/sAML. Some studies suggest a high baseline blast percentage may portend a worse prognosis in AML. This post hoc analysis of phase 3 data assessed outcomes by baseline BM blast percentage. Methods: Pts diagnosed with AML per 2008 WHO criteria (≥20% blasts in peripheral blood or BM) were randomized 1:1 to receive ≤2 inductions of CPX-351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] on Days 1, 3, 5 [2nd induction: Days 1, 3]) or 7+3 (C 100 mg/m2/d continuously for 7 d [2nd induction: 5 d] + D 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive ≤2 consolidations. Results: CPX-351 had longer median OS and higher remission rates vs 7+3 irrespective of baseline BM blast percentage; median OS was worse in higher blast groups for both treatments (Table). The incidence of grade ≥3 TEAEs was >80% for both arms; febrile neutropenia was the most common. Conclusions: Improved outcomes were observed with CPX-351 vs 7+3 irrespective of baseline BM blast percentage in older adults with newly diagnosed high-risk/sAML. Clinical trial information: NCT01696084. [Table: see text]

7040Background: CPX-351, a liposomal encapsulation of cytarabine (C) and daunorubicin (D) at a synergistic ratio, is approved in the US for treatment of adults with newly diagnosed therapy-related ...

e18507 Background: FLT3+ AML patients (pts; 20%-30% of AML pts) often have rapid post-induction relapse, highlighting the need for therapies that improve the bridge to SCT. CPX-351 is a liposomal formulation that delivers a synergistic 5:1 molar ratio of cytarabine (C) and daunorubicin (D). CPX-351 demonstrated efficacy versus 7+3 in a randomized, open-label, controlled phase III trial in pts aged 60-75 years with newly diagnosed, high-risk AML; our analysis investigated outcomes in the subset of FLT3+ pts. Methods: Pts were randomized 1:1 to induction with 1-2 cycles of CPX-351 (100 u/m2 [C 100 mg/m2 + D 44 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/day x 7 days [2nd induction: x 5 days] + D 60 mg/m2on Days 1, 2, and 3 [2nd induction: Days 1 and 2]). Pts with complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 consolidation cycles. Results: Of the pts who had FLT3 mutations assessed and received study treatment, 22/138 (16%) pts in the CPX-351 arm and 20/136 (15%) pts in the 7+3 arm had baseline FLT3 mutations. AML subtypes in FLT3+ pts were: tAML (19%); AML after MDS with (38%) or without (10%) prior hypomethylating agents; AML after CMMoL (12%); and de novo AML with MDS karyotype (21%). In FLT3+ pts, median OS was longer with CPX-351 (10.25 mo) versus 7+3 (4.55 mo; HR = 0.57 [95% CI: 0.24, 1.33]; P= 0.093) and the rate of CR+CRi was higher (68% vs 25%). A greater number of FLT3+ pts treated with CPX-351 were able to undergo SCT (n = 10/22 [45%]; 4 pts were alive as of this analysis, after a median post-SCT follow up of 692 days [range: 96-769]) compared with 7+3 (n = 2/20 [10%]; neither pt still alive). The on-study safety profile of CPX-351 in FLT3+ pts was comparable to 7+3 and consistent with the overall study population. Serious adverse events were experienced by 7 (32%) FLT3+ pts in the CPX-351 arm and 10 (50%) in the 7+3 arm. Conclusions: CPX-351 demonstrated numerical improvement in median OS in older pts with newly diagnosed, FLT3+ high-risk AML and allowed more pts to undergo SCT. The analysis was limited by small number of pts. Clinical trial information: NCT01696084.

7036 Background: The CPX-351 liposomal formulation delivers a synergistic 5:1 molar ratio of cytarabine (C) and daunorubicin (D) preferentially to leukemia cells. CPX-351 has demonstrated significantly improved overall survival (OS) versus 7+3 in a randomized, open-label, phase III study in patients (pts) aged 60-75 years with newly diagnosed, high-risk AML. In contrast to 7+3, which includes C continuous infusion, CPX-351 is administered as a 90-minute infusion and has the potential to be given in the outpatient setting. The current analysis of the phase III trial assessed the setting of consolidation therapy. Methods: Pts were randomized 1:1 to 1-2 induction cycles of CPX-351 or 7+3; pts with complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 consolidation cycles (CPX-351: 65 u/m2 [C 65 mg/m2 + D 28.6 mg/m2] on Days 1 and 3; 7+3: C 100 mg/m2/day x 5 days + D 60 mg/m2 on Days 1 and 2). Site of administration was not protocol defined. Results: Few pts received induction as outpatient therapy (CPX-351 n = 3/153 and 7+3 n = 1/151 in each cycle). 49/153 CPX-351 pts and 32/151 7+3 pts received consolidation, with a substantial proportion of pts receiving CPX-351 as outpatients (consolidation 1: 51%; consolidation 2: 61%). CPX-351 consolidation was associated with substantial improvement in median OS versus 7+3 irrespective of inpatient/outpatient status (Table). Median OS was not diminished with CPX-351 administration in the outpatient versus inpatient setting (consolidation 1: 25.43 and 14.72, respectively; consolidation 2: 26.32 and not reached). Conclusions: Some pts can successfully receive CPX-351 consolidation as outpatients without diminished efficacy, potentially reducing hospitalizations associated with treatment administration. Clinical trial information: NCT01696084. [Table: see text]

7035 Background: tAML may occur as a late complication of cytotoxic therapy and is associated with a poor prognosis. CPX-351 is a liposomal formulation that delivers a synergistic 5:1 molar ratio of cytarabine (C) and daunorubicin (D). In a randomized, open-label, controlled phase III trial in patients (pts) aged 60-75 years with newly diagnosed, secondary AML (tAML or after MDS), CPX-351 significantly improved OS versus 7+3. The current analysis of this phase III study evaluated outcomes in the subgroup of pts with tAML. Methods: Pts were randomized 1:1 to induction with 1-2 cycles of CPX-351 (100 u/m2 [C 100 mg/m2 + D 44 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/day x 7 days [2nd induction: x 5 days] + D 60 mg/m2on Days 1, 2, and 3 [2nd induction: Days 1 and 2]). Pts with complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 cycles of consolidation therapy. The study was not powered for this subgroup analysis. Results: 304 pts were enrolled and received study treatment, including 62 (20%) pts with tAML; demographics of tAML pts were similar between study arms. Pts with tAML had typically received prior non-anthracycline chemotherapy alone (25%), radiation alone (25%), or non-anthracycline chemotherapy + radiation (32%). CPX-351 was associated with an OS benefit versus 7+3 in older tAML pts and numerically longer event-free survival (EFS) and remission duration (Table). A greater proportion of tAML pts achieved CR+CRi (47% vs 36%, respectively) and proceeded to stem cell transplantation (37% vs 27%) with CPX-351. The safety profile of CPX-351 was comparable to that of 7+3. Conclusions: CPX-351 is associated with improved outcomes in older pts with newly diagnosed tAML. Outcomes in the tAML subgroup mirrored the overall study population, indicating CPX-351 may represent a new therapeutic option for this difficult to treat population. Clinical trial information: NCT01696084. [Table: see text]

7000Background: Older patients with secondary AML have poor outcomes following first-line cytarabine and anthracycline-based treatment. CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio with enhanced efficacy among poor risk AML patients. We report final results from a randomized open-label study of first-line CPX-351 in patients with high-risk sAML (NCT01696084). Methods: Patients 60-75 years of age with untreated AML with a history of prior cytotoxic treatment, antecedent MDS or CMML (+/- prior hypomethylator treatment), or AML with WHO-defined MDS-related cytogenetic abnormalities were eligible. 300 patients were to be randomized 1:1 to CPX-351 (100 units/m2, days 1, 3, 5) or 7+3 (cytarabine 100 mg/m2/day x 7 days, daunorubicin 60 mg/m2 days 1, 2, 3) induction therapy. Endpoints included: overall (OS, 1o) and event free survival (EFS) assessed by stratified log rank analysis, independent blinded assessment of CR+CRi, and 60-day mortality. Patient enroll...

6601 Background: A Phase 2b study randomized untreated elderly AML pts to CPX-351 or 7+3. CPX-351 improved leukemia clearance (88% v 71%, Cr < 2.0 mg/dL, total bilirubin 2; D 1, 3, 5; 90 min infusion) or 7+3 (cytarabine=100 mg/m2 and daunorubicin=60 mg/m2). Consolidation with stem cell transplantation (SCT) was permitted. The 1o endpoint was CR+CRi rate. The 7+3 control arm had only a single CRi among 21 responders. The CPX-351 arm had 15 CRi (27%) and 41 CR (73%) allowing a CR v CRi comparison to be made. Results: CR and CRi pts were balanced by age, race, and PS. The CRi group had more males (87% v 51%), more baseline WBC>20K (27% v 15%), and more adverse karyotype (40% v 27%) and sAML (47% v 29%). A smaller proportion of CRi pts received post-remission chemotherapy (47% v 73%) but had similar rates of SCT (13% v 20%). Most CRi pts had delayed platelet recovery (80%). By 1-year more CRi pts had relapsed (54% v 39%) and more had died (54% v 34%). Contributing causes included: relapsed AML (7 CRi v 10 CR pts), complications post SCT (1 CRi v 1 CR pt), chemotherapy complications (0 CRi v 2 CR pts) and unknown causes (0 CRi v 1 CR pt). The survival curves were not significantly different (p=0.39). Conclusions: More CRi patients had adverse karyotype and sAML and most (53%) received no post remission chemotherapy. Survival was not significantly different compared to CR patients but was markedly better than that of non-responders. These data suggest that CRi following CPX-351 provides clinically meaningful benefit, a finding that needs to be confirmed in a larger randomized study.