CPX-351 Arm Research Articles

Evaluation of treatment outcomes with CPX-351 in adults with AML: A meta-analysis.

6540 Background: CPX-351 is a liposomal formulation of cytarabine and daunorubicin which has shown survival benefit when compared to 7+3 in older adults with myelodysplasia-related (AML-MRC) and therapy-related AML (t-AML). Aiming to investigate the clinical efficacy of CPX-351 against 7+3 in adults with AML, we performed a meta-analysis. Methods: A systematic search with controlled vocabulary encompassing AML, CPX-351 and 7+3 was conducted in PubMed, Embase, Scopus, and Cochrane on November 1, 2023 with no search restrictions. 3461 were found; 2581 were left after duplicates were removed using Mendeley 1.19.8. Remaining records were imported into Rayyan and independently screened by 2 reviewers. 8 studies were included in the analysis as they provided data for both CPX-351 and 7+3. 17 studies only including CPX-351 were identified. RevMan was used to analyze the Odds Ratio (OR) with 95% Confidence Interval (CI), derived from random effects (RE) model with Mantel-Haenszel (MH) method. Results: We identified 8 studies comparing CPX-351 to 7+3, encompassing a total of 1368 total patients: 44% (604/1368) received CPX-351, 56% (764/1368) received 7+3. Most patients had AML-MRC or t-AML. The median age in the CPX-351 group was 66 (range 58-67) and in the 7+3 group was 67 (range 58-67). The median overall survival grossly favored CPX-351 with 10.3 months (range 8.8-22 months) compared to 6.2 months (range 4.6-12 months) in 7+3. The OR of complete remission (CR) for CPX-351 versus 7+3 using the RE model was 1.66 (CI=1.15-2.39, p=0.006, I2=55%). Similarly, the OR of patients undergoing hematopoietic stem cell transplantation (HSCT) for CPX-351 versus 7+3 was 1.52 (CI=1.01-2.30, p=0.05, I2=47%). Including the additional 17 studies with CPX-351, the overall CR rate for all patients was 49%. Average 30-day mortality with CPX-351 was 4.9%. Conclusions: From our analysis, the OR of attaining CR and HSCT were shown to be significantly improved with CPX-351 when compared to conventional 7+3 chemotherapy in adult patients with AML. Both groups had similar median age, and patients in the CPX-351 arm had longer median overall survival. Our meta-analysis highlights that while CPX-351 achieves CR/HSCT at a higher rate than 7+3, data in younger populations (<60 years old) and patients with de novo AML are sparse. Heterogeneity between studies and lack of mutational analysis are limitations of our study. [Table: see text]

Real World Outcomes of CPX-351 Compared to Traditional Chemotherapy with Cytarabine Consolidation for Treatment of Secondary Acute Myeloid Leukemia

Introduction: Outcomes in patients with secondary AML (sAML) are inferior to those with de novo AML which has led investigators to seek alternatives to traditional treatment. Liposomal daunorubicin and cytarabine, or CPX-351, for the treatment of sAML has shown superior complete remission/complete remission with incomplete count recovery (CR/CRi), event-free survival (EFS), and overall survival (OS) compared to the traditional non-liposomal formulations of daunorubicin and cytarabine (“7+3”). However, this agent was originally studied in combination with a suboptimal consolidation regimen which did not include standard of care high dose cytarabine (HiDAC). This is often cited as a limitation of the study and may have contributed to the significantly lower response rates reported when compared to historical data. Here we present a real-world comparison of the efficacy and safety of patients with sAML receiving CPX-351 versus traditional 7+3 with HiDAC consolidation. Methods: Patients were at least 18 years of age with sAML, defined as: t-AML, AML-with Myelodysplasia-Related Changes (MRC), or AML with a history of chronic myelomonocytic leukemia (CMML). Patients were included if they had received induction (and consolidation, if applicable) with CPX-351 or induction with 7+3 (daunorubicin 60 mg/m 2 for 3 days and cytarabine 100 mg/m 2 for 7 days), followed by consolidation with cytarabine (≥1000 mg/m 2 x 6 doses). Nominal data were analyzed using chi squared tests or Fisher's exact tests. Continuous data were analyzed using the Mann-Whitney U test. A Kaplan Meier estimator was used for survival outcomes. Results: Overall, 58 patients with sAML were included, with 36 (62%) receiving CPX-351 and 22 (38%) receiving 7+3 followed by cytarabine-based consolidation between April 2013 and June 2022. Patients in the CPX-351 were older (67.5 vs 62 years, p=0.04) and had a higher prevalence of poor-risk cytogenetics (p=0.22). Other baseline characteristics were similar (Table 1). The rate of CR/CRi following induction was significantly higher in patients who received 7+3-based induction vs patients who received CPX-351 (81.8% vs 44.4%, p=0.01). Twenty-five percent of patients achieved CR/CRi in the CPX-351 arm with one induction cycle, compared to 95.5% in the 7+3 group. Median progression-free survival (PFS) was 3 vs 6.1 months (p=0.67) and median OS was 18.3 vs 9.3 months (p=0.73) in the CPX-351 and 7+3 cohorts, respectively (Figure 1). Thirty-nine percent of patients in the 7+3 cohort proceeded to allogeneic stem cell transplant compared to 81% in the CPX-351 cohort, however median OS in patients who underwent transplant was similar between the two cohorts (16.8 vs 15.8 months). Median OS was longer in the CPX-351 cohort however this was not statistically significant (Figure 1). Rates of both febrile neutropenia (94.3% vs 95.5%; P>0.99) and confirmed infections (54.3% vs 50%) were similar amongst those treated with CPX-351 and 7+3. Bacteremia and pneumonia were the most common infections in both cohorts. Median duration of neutropenia was significantly longer in the CPX-351 cohort (43 days vs. 27 days, p=0.002) with no major difference in duration of thrombocytopenia. In the 7+3 cohort, 11 deaths were directly attributed to progression, while 5 were associated with infection. In the CPX-351 cohort, 6 deaths were directly attributed to progression, while 8 were attributed to infection. At day 60, two deaths were observed in the CPX-351 cohort and there were no deaths in the 7+3 cohort. Conclusion: These findings suggest use of traditional 7+3 induction followed by HiDAC consolidation may be an alternative to CPX-351 for patients with sAML. Although median PFS was longer in the 7+3 cohort, this did not translate into longer median OS, likely due to the low rate of patients proceeding to transplant. Similar rates of overall survival in patients undergoing allogeneic stem cell transplantation support the hypothesis that transplant should be the goal for most patients with sAML. The retrospective nature of the study may limit broader application of this data.

Cost-Effectiveness of Liposomal Cytarabine-Daunorubicin (CPX-351) Compared to Conventional Cytarabine-Daunorubicin Chemotherapy in Acute Myeloid Leukemia

Cost-Effectiveness of Liposomal Cytarabine-Daunorubicin (CPX-351) Compared to Conventional Cytarabine-Daunorubicin Chemotherapy in Acute Myeloid Leukemia

Rates of Adverse Events per Patient-Year in a Randomized, Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed, Treatment-Related Acute Myeloid Leukemia (AML) or AML with Myelodysplasia-Related Changes

Rates of Adverse Events per Patient-Year in a Randomized, Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed, Treatment-Related Acute Myeloid Leukemia (AML) or AML with Myelodysplasia-Related Changes

Subanalysis of Patients with Secondary Acute Myeloid Leukemia (sAML) with Refractory Anemia with Excess of Blasts in Transformation (RAEB-t) Enrolled in a Phase 3 Study of CPX-351 Versus Conventional 7+3 Cytarabine and Daunorubicin

Subanalysis of Patients with Secondary Acute Myeloid Leukemia (sAML) with Refractory Anemia with Excess of Blasts in Transformation (RAEB-t) Enrolled in a Phase 3 Study of CPX-351 Versus Conventional 7+3 Cytarabine and Daunorubicin

CPX-351 Exposure-Response Based on Cumulative Dose of Cytarabine and Daunorubicin in Patients with Newly Diagnosed, Treatment-Related Acute Myeloid Leukemia (AML) or AML with Myelodysplasia-Related Changes

▪CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio. Intact CPX-351 liposomes containing the synergistic ratio are taken up by leukemia cells to a greater extent versus normal bone marrow cells, have a high retention of drug cargo, and have a long plasma half-life. In a phase 3 study in older adults with newly diagnosed, treatment-related AML or AML with myelodysplasia-related changes, CPX-351 demonstrated significantly improved overall survival and response rates compared with conventional 7+3 chemotherapy and a safety profile consistent with that of 7+3. Cumulative lifetime exposure to daunorubicin is associated with risks of cardiotoxicity. Therefore, it was of interest to determine if the superior efficacy observed with CPX-351 versus 7+3 was achieved with lower cumulative doses of cytarabine and daunorubicin relative to 7+3. An exposure-response analysis was conducted to document the relationships of cumulative doses of cytarabine and daunorubicin with efficacy outcomes for CPX-351 versus 7+3 therapy.Efficacy and cumulative exposure data were obtained from the phase 3 study CLTR0310-301 (NCT01696084), in which patients were randomized 1:1 to receive CPX-351 or 7+3 induction therapy. Cumulative dose corresponded to the total amount of drug (mg of cytarabine or daunorubicin) administered to an individual patient during the entire time that patient remained on the study. The clinical endpoints for efficacy were overall survival, complete remission (CR), and CR + CR with incomplete hematologic recovery (CR+CRi).A total of 309 patients were enrolled in the study; the exposure-response analysis for cumulative dose included 153 patients treated with CPX-351 and 149 patients treated with 7+3. Baseline characteristics were generally similar between the CPX-351 and 7+3 cohorts. In the overall study population, median duration of the treatment was 62 days in the CPX-351 arm and 41 days in the 7+3 arm. The most common reason for discontinuation among patients included in this analysis was lack of efficacy, but the incidence was lower for the CPX-351 cohort (34.6%) than for the 7+3 cohort (49.0%). In the exposure-response analysis for overall survival, patients treated with CPX-351 who were alive at the data cut-off time for the primary endpoint analysis (n = 47) tended to have received less cytarabine and daunorubicin than those treated with 7+3 (n = 23). The mean cumulative doses of cytarabine and daunorubicin for patients alive in the CPX-351 cohort were 61.9% and 76.8%, respectively, of cumulative doses for patients alive in the 7+3 cohort (Table). Among responders classified as achieving a CR or CR+CRi, those treated with CPX-351 tended to receive less cytarabine and daunorubicin than those treated with 7+3 chemotherapy. The mean cumulative doses of cytarabine and daunorubicin for patients who achieved a CR in the CPX-351 cohort were 26.5% and 63.2%, respectively, of cumulative doses for patient with CR in the 7+3 cohort, and the mean cumulative doses for patients who achieved a CR+CRi in the CPX-351 cohort were 36.2% and 65.1%, respectively, of those with CR+CRi in the 7+3 cohort (Table). For non-responders or deceased patients, the mean cumulative doses of cytarabine and daunorubicin similarly tended to be lower in patients who received CPX-351 than in those who received 7+3 therapy. The finding that a lower cumulative dose of cytarabine and daunorubicin in CPX-351 relative to standard 7+3 therapy led to improved efficacy and increased on-target myelosuppression supports the observation in animal models that CPX-351 is taken up in the bone marrow by leukemia cells to a greater extent than normal cells.Taken together, the results of this exposure-response analysis show that the mean cumulative doses of cytarabine and daunorubicin associated with an overall survival benefit were lower with CPX-351 than with 7+3, as were the mean cumulative doses associated with achieving a CR or CR+CRi. Thus, compared with 7+3, CPX-351 was associated with improved efficacy at a reduced total drug burden in this population of older adults with newly diagnosed, treatment-related AML or AML with myelodysplasia-related changes. [Display omitted] DisclosuresBanerjee:Celator/Jazz: Employment, Equity Ownership. Wang:Celator/Jazz: Employment, Equity Ownership. Wang:Celator/Jazz: Consultancy. Gibbons:Celator/Jazz: Employment, Equity Ownership.

Cost-Effectiveness of CPX-351 Versus 7+3 Regimen in the Treatment of Treatment-Related Acute Myeloid Leukemia (tAML) or AML with Myelodysplasia-Related Changes (MRC)

CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic drug ratio. In a phase 3 trial (NCT01696084) in elderly patients with newly diagnosed tAML or AML-MRC, CPX-351 demonstrated superior overall survival (9.56 vs 5.95 months; HR = 0.69; P= 0.005) and significantly improved complete remission rate (38% vs 26%; P= 0.040) compared to the 7+3 regimen of cytarabine and daunorubicin, the current standard of care for remission induction. These clinical improvements may increase the cost of caring for patients with AML through higher drug costs, increased numbers of patients receiving hematopoietic cell transplant (HCT), and the costs of disease management during extended survival. In an era of increased scrutiny of drug costs and health care budgets, it is essential to understand the balance of clinical benefits and costs associated with treatment of AML using CPX-351.A health economic model with a lifetime time horizon was developed comparing the costs and outcomes of CPX-351 to those of 7+3 in the treatment of AML from the perspective of a US commercial payer. The model was developed in accordance with good modeling practice guidelines and recommendations of the US Second Panel on Cost-Effectiveness in Health and Medicine. The model considered a patient population stratified by age and AML subtype based on the CPX-351 phase 3 clinical trial design. Within each subpopulation, patients were distributed among potential treatment pathways in accordance with observed trial data. Treatment pathways in the model were defined in terms of whether or not patients responded following induction and whether or not patients received an HCT. The numbers of induction and consolidation cycles were also tracked. The model then projected overall and event-free survival over patients' lifetimes based on the patients' characteristics and treatment pathways using statistical extrapolation of observed data from the clinical trial. Specifically, for each treatment pathway, a parametric survival function was fit to the observed data with patient characteristics, treatment arm, cycles of induction, and cycles of consolidation included as risk factors. These survival functions were then applied in the model for each subpopulation and summed to estimate the overall clinical outcomes for the full population. Costs of drugs were assigned based on published sources for 7+3 and manufacturers' estimates for CPX-351. Costs of non-pharmaceutical management were estimated based on DRG coding and published literature. Quality of life at different disease stages was assessed using the time trade-off method in vignette-based interviews.We found that treatment with CPX-351 was projected to provide an additional 1.9 years of life compared to 7+3 (2.8 vs 0.9 years, respectively). These gains reflected shifts among the treatment pathways, particularly a larger fraction of patients receiving HCT with CPX-351 than with 7+3, and longer survival within pathways among patients who responded to induction therapy. While the CPX-351 treatment arm demonstrated increased numbers of responders, non-responders had no difference in outcomes between the arms in the model. When accounting for the quality of life of patients with different stages of AML, the additional life years were equivalent to an incremental increase of 1.02 quality-adjusted life years (QALYs) compared to 7+3. Patients in the CPX-351 arm incurred a total incremental cost of $113,658 compared to 7+3, primarily due to pharmacy costs and costs associated with the larger number of HCTs. Taken together, these costs and improved clinical outcomes yield an incremental cost-effectiveness ratio (ICER) of $111,385/QALY gained over 7+3.These results suggest a favorable balance between the clinical gains and incremental costs of treatment with CPX-351 versus the 7+3 standard of care and demonstrate that CPX-351 is a cost-effective option in the treatment of patients with tAML or AML-MRC. DisclosuresKansal:Celator/Jazz: Consultancy. Du:Celator/Jazz: Consultancy. Herrera-Restrepo:Celator/Jazz: Consultancy. Leipold:Celator/Jazz: Consultancy. Ryan:Celator/Jazz: Employment, Equity Ownership. Louie:Celator/Jazz Pharmaceuticals, Inc.: Employment, Equity Ownership, Patents & Royalties. Chung:Bayer: Equity Ownership; Amgen: Equity Ownership; Baxalta: Equity Ownership; Gilead: Employment; Shire: Equity Ownership; Baxter: Equity Ownership; Gilead: Equity Ownership; Jazz Pharmaceuticals: Employment, Equity Ownership.

Multicenter comparison of high-dose cytarabine-based regimens versus liposomal daunorubicin and cytarabine (CPX-351) in patients with secondary acute myeloid leukemia

Liposomal daunorubicin/cytarabine (CPX-351) gained FDA approval for secondary AML after demonstrating improved outcomes over daunorubicin and cytarabine (7 + 3). A number of study limitations prompted a comparison of safety/efficacy of CPX-351 against regimens containing a purine analogue and high-dose cytarabine (HIDAC). This retrospective study compared complete response rates with/without count recovery (CR/CRi) between HIDAC-based regimens and CPX-351 in 169 patients with newly diagnosed sAML. The CR/CRi rate was 62.7% in the HIDAC-based therapy arm vs. 47.9% in the CPX-351 arm (p = 0.002 [one-sided for non-inferiority]). Median time to absolute neutrophil and platelet count recovery was shorter after HIDAC-based therapy (18 and 23 days, respectively) compared to CPX-351 (36 and 38 days; p < 0.001). Median overall survival was 9.8 months in the HIDAC-based group and 9.14 months in the CPX-351 group. 30-day mortality was greater with CPX-351 (8.5%) compared to HIDAC-based (1.3%; p = 0.039). These results reveal comparable efficacy and favorable safety with HIDAC-based regimens.

Higher Dose of CPX-351 Is Associated with Prolonged Hematologic Recovery: Results from an Interim Safety Analysis of the Randomized, Phase III AMLSG 30-18 Trial

Higher Dose of CPX-351 Is Associated with Prolonged Hematologic Recovery: Results from an Interim Safety Analysis of the Randomized, Phase III AMLSG 30-18 Trial

Clinical Outcomes of Patients with Secondary Acute Myeloid Leukemia (sAML) Treated with Hypomethylating Agent Plus Venetoclax (HMA-Ven) or Liposomal Daunorubicin Cytarabine (CPX-351)

Clinical Outcomes of Patients with Secondary Acute Myeloid Leukemia (sAML) Treated with Hypomethylating Agent Plus Venetoclax (HMA-Ven) or Liposomal Daunorubicin Cytarabine (CPX-351)

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients Enrolled in CPX-351-301, a Randomized Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed, High-Risk and/or Secondary AML

Background: CPX-351 is a liposomal encapsulation of daunorubicin and cytarabine in a 1:5 molar ratio. In a randomized phase 3 study (CPX-351-301) conducted in older adults (60 to 75 years old) with newly diagnosed, high-risk and/or secondary AML, CPX-351 induction therapy was superior to standard 7+3 with improved rates of complete remission (CR) and overall survival (OS). In both older adults and high-risk AML, allogeneic hematopoietic cell transplantation (HCT) is frequently the preferred post-remission strategy owing to the high rates of relapse and poor overall survival with conventional chemotherapy approaches. After a median follow-up of 20.7 months, the primary pre-planned analysis found that more patients randomized to CPX-351 underwent HCT and an exploratory landmark survival analysis from the time of HCT favored CPX-351 (HR = 0.46 [95% CI: 0.24, 0.89]; one-sided P = 0.009). However, the initial protocol did not collect data related to HCT and the basis for improved HCT outcomes with CPX-351 was previously unknown. Here we present a detailed analysis of HCT outcomes in patients enrolled in the CPX-351-301 study with 5-years of follow-up. Methods: Patients age 60 to 75 years with high-risk and/or secondary AML were randomized in a 1:1 fashion to receive CPX-351 or 7+3 as induction and consolidation chemotherapy (Lancet J et al, JCO 2018). The protocol was amended to collect additional HCT-specific information, including donor and HCT characteristics and post-HCT outcomes, including rates of relapse and GVHD. Post-HCT outcomes including relapse, GVHD, and death were analyzed as competing events. Results: Of 309 randomized patients in the CPX-351-301 study, more patients achieved CR/CRi with CPX-351 vs 7+3 (48% vs 33%) allowing more patients to proceed to HCT (35% vs 25%) and more patients to proceed to HCT in remission (CPX-351: 41/73 [56%]; 7+3: 24/52 [46%]). The median age was 66 years with CPX-351 vs 65 years with standard induction among the transplanted cohorts; 16 patients in the CPX-351 transplanted arm were over the age of 70 compared to only 6 in the 7+3 arm. Other pre-HCT patient characteristics were balanced between the CPX-351 and 7+3 groups, including ECOG performance status (8% vs 5% with ECOG PS of 2), HCT-CI (median 4 vs 3), donor type (matched unrelated donor 49% vs 49%), and conditioning regimen intensity (myeloablative [17% vs 13%] vs reduced-intensity conditioning [43% vs 46%]). The Kaplan-Meier-estimated 3-year survival rate among transplanted patients was 56% with CPX-351 vs 23% with 7+3 (Figure 1A). The differences in survival consistently favored CPX-351 across patient age, AML subtype, disease status, donor type, and conditioning intensity (Figure 1B). Differences in OS were driven by a large reduction in non-relapse mortality (HR = 0.42 [95% CI: 0.21, 0.86]; Figure 1D). The cumulative incidence of acute GVHD with death as a competing event at 6 months from HCT date was 0.49 (95% CI: 0.35, 0.62) in the CPX-351 arm and 0.38 (95% CI: 0.23, 0.53) in the 7+3 arm. Conclusions: Analysis of HCT outcomes in patients enrolled in the CPX-351-301 study demonstrated that treatment with CPX-351 in older adults with high-risk and/or secondary AML resulted in more patients bridged to HCT and more patients transplanted in CR/CRi compared to 7+3, with improved OS in transplanted patients. The pattern of HCT outcomes suggests improved disease control with CPX-351 induction allowing higher HCT rates, but more importantly improved tolerability with less non-relapse mortality; this data supports the development of CPX-351 in other high-risk AML populations in which allogeneic HCT is the preferred post-remission strategy. Figure Disclosures Uy: Genentech: Consultancy; Agios: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Astellas Pharma: Honoraria; Jazz Pharmaceuticals: Consultancy. Lin:Abbvie: Research Funding; Pfizer: Research Funding; Trovagene: Research Funding; Prescient Therapeutics: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; Ono Pharmaceutical: Research Funding; Genetech-Roche: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Gilead Sciences: Research Funding; Celyad: Research Funding; Celgene: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Aptevo: Research Funding. Wieduwilt:Reata Pharmaceuticals: Current equity holder in publicly-traded company; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Merck: Research Funding; Leadiant: Research Funding; Amgen: Research Funding; Macrogeneics: Research Funding. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Faderl:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lancet:Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy.

Outcomes in older patients with high-risk/secondary AML who achieved remission with CPX-351 versus 7+3 but did not undergo transplant: Phase 3 exploratory analysis.

7537 Background: CPX-351 (Vyxeos; daunorubicin [D] and cytarabine [C] liposome for injection) is approved by the FDA and EMA for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. In a phase 3 study (NCT01696084) in patients (pts) aged 60-75 y with newly diagnosed high-risk/secondary AML, CPX-351 demonstrated significantly longer overall survival (OS) and higher rates of remission and hematopoietic cell transplant (HCT) vs conventional 7+3, with a comparable safety profile. To better understand the impact of treatment on outcomes in pts who did not undergo HCT, this exploratory analysis evaluated outcomes in the subgroup who achieved complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CRi) with CPX-351 vs 7+3 but did not undergo HCT. Methods: Pts were randomized 1:1 to receive ≤2 induction cycles of CPX-351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] as a 90-min infusion on Days 1, 3, 5 [2nd induction: Days 1, 3]) or 7+3 (C 100 mg/m2/d continuously for 7 d + D 60 mg/m2 on Days 1-3 [2nd induction: 5+2]). Pts achieving CR or CRi could receive up to 2 consolidation cycles. Pts could receive HCT at the physician’s discretion. Results: CR+CRi was achieved by 73/153 (48%) pts with CPX-351 vs 52/156 (33%) with 7+3; of these pts, 33/73 (45%) vs 28/52 (54%) did not subsequently undergo HCT. The baseline characteristics of these pts were generally balanced between arms; however, the CPX-351 arm had more male pts vs 7+3 (64% vs 43%) and pts with ECOG PS of 1 (82% vs 54%), and fewer pts with antecedent MDS and HMA exposure (21% vs 39%). Median OS was longer with CPX-351 vs 7+3 (14.72 vs 7.59 mo; HR = 0.57 [95% CI: 0.31-1.03]; Table). There was no early mortality by Day 60 in either arm (see Table for additional data). Conclusions: CPX-351 improved median OS vs 7+3 in pts who achieved CR+CRi but did not undergo HCT, suggesting a treatment benefit with CPX-351 even among pts who do not undergo HCT. The CPX-351 safety profile in this subgroup was consistent with the overall study population and known profile of 7+3. Clinical trial information: NCT01696084 . [Table: see text]

Phase 3 Exploratory Analysis of Outcomes in Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Who Received Consolidation with CPX-351 Versus Conventional Chemotherapy

Phase 3 Exploratory Analysis of Outcomes in Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Who Received Consolidation with CPX-351 Versus Conventional Chemotherapy

Outcomes in Patients with Therapy-Related Acute Myeloid Leukemia (t-AML) Who Achieved Remission with CPX-351 Versus 7+3: Phase 3 Exploratory Analysis

Outcomes in Patients with Therapy-Related Acute Myeloid Leukemia (t-AML) Who Achieved Remission with CPX-351 Versus 7+3: Phase 3 Exploratory Analysis

Genetic Characteristics and Outcomes By Mutation Status in a Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed, High-Risk/Secondary Acute Myeloid Leukemia (AML)

Lindsley: Jazz Pharmaceuticals: Research Funding; Takeda Pharmaceuticals: Consultancy; Medlmmune: Research Funding. Stone:AbbVie, Actinium, Agios, Argenx, Arog, Astellas, AstraZeneca, Biolinerx, Celgene, Cornerstone Biopharma, Fujifilm, Jazz Pharmaceuticals, Amgen, Ono, Orsenix, Otsuka, Merck, Novartis, Pfizer, Sumitomo, Trovagene: Consultancy; Argenx, Celgene, Takeda Oncology: Other: Data and Safety Monitoring Board/Committee: ; Novartis, Agios, Arog: Research Funding. Cortes:Astellas Pharma: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; BiolineRx: Consultancy; Sun Pharma: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding. Uy:GlycoMimetics: Consultancy; Astellas: Consultancy; Curis: Consultancy; Pfizer: Consultancy. Lin:Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria. Ritchie:Celgene, Incyte, Novartis, Pfizer: Consultancy; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Celgene, Novartis: Other: travel support; Jazz Pharmaceuticals: Research Funding; Genentech: Other: Advisory board; Celgene: Other: Advisory board; Pfizer: Other: Advisory board, travel support; agios: Other: Advisory board; Tolero: Other: Advisory board. Prebet:novartis: Honoraria; pfizer: Honoraria; pfizer: Honoraria; novartis: Honoraria; Boehringer Ingelheim: Research Funding. Ryan:Jazz Pharmaceuticals: Employment, Equity Ownership. Faderl:Jazz Pharmaceutics: Employment, Equity Ownership. Lancet:Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Other: fees for non-CME/CE services ; Agios, Biopath, Biosight, Boehringer Inglheim, Celator, Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm, Novartis: Consultancy.

Hypomethylating Agent and Venetoclax Combination Yields Comparable Outcomes to CPX-351 in Newly Diagnosed Acute Myeloid Leukemia

Hypomethylating Agent and Venetoclax Combination Yields Comparable Outcomes to CPX-351 in Newly Diagnosed Acute Myeloid Leukemia

The Impact of Hematopoietic Cell Transplantation on Survival: An Exploratory Analysis of a Phase 3 Study of CPX-351 Versus 7+3 in Older Patients with Newly Diagnosed, High-Risk/Secondary AML

The Impact of Hematopoietic Cell Transplantation on Survival: An Exploratory Analysis of a Phase 3 Study of CPX-351 Versus 7+3 in Older Patients with Newly Diagnosed, High-Risk/Secondary AML

Efficacy and Safety of CPX-351 Versus 7+3 in a Subgroup of Older Patients with Newly Diagnosed Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Enrolled in a Phase 3 Study

Efficacy and Safety of CPX-351 Versus 7+3 in a Subgroup of Older Patients with Newly Diagnosed Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Enrolled in a Phase 3 Study

Overall survival (OS) and stem cell transplant (SCT) in patients with FLT3 mutations treated with CPX-351 versus 7+3: Subgroup analysis of a phase III study of older adults with newly diagnosed, high-risk acute myeloid leukemia (AML).

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.

Analysis of Efficacy By Age for Patients Aged 60-75 with Untreated Secondary Acute Myeloid Leukemia (AML) Treated with CPX-351 Liposome Injection Versus Conventional Cytarabine and Daunorubicin in a Phase III Trial

Analysis of Efficacy By Age for Patients Aged 60-75 with Untreated Secondary Acute Myeloid Leukemia (AML) Treated with CPX-351 Liposome Injection Versus Conventional Cytarabine and Daunorubicin in a Phase III Trial