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Overall survival is more than double at 5 years with VYXEOS (18%) vs 7+3 (8%) based on KM estimates1,2

Median overall survival (primary analysis) of 9.6 months with VYXEOS vs 5.9 months with 7+3, reducing the risk of death by 31% (HR=0.69 [95% CI: 0.52, 0.90], P=0.005a)1

5-Year Follow-Up

Kaplan-Meier curve for overall survival, ITT population2

VYXEOS overall survival KM curve
1-Year KM-estimated overall survival3
VYXEOS: 42% 7+3: 28%
5-Year KM-estimated overall survival2
VYXEOS: 18% 7+3: 8%

Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.

See full study design

This prospectively planned overall survival analysis of the ITT population was conducted based on the final 5-year follow-up results from the Phase 3 trial2

aP value is 2-sided.1

 

Exploratory post hoc analysis

At 5 years, median overall survival was longer with VYXEOS vs 7+3 in patients aged 60-69 and 70-75 years2

5-YEAR FOLLOW-UP

Kaplan-Meier curve for overall survival by age subgroup, aged 60 to 69 years4

KM Curve: 60-69 years

Median overall survival (95% CI):

VYXEOS: 9.6 months (6.0, 12.6) (n=76/96)

7+3: 6.9 months (4.6, 8.8) (n=91/102)

Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.

Age was prospectively stratified in the initial analysis of the Phase 3 trial2

See full study design

See the Phase 3 Study Safety Profile

Limitations of subanalysis

  • This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS can be drawn from this analysis

5-YEAR FOLLOW-UP

Kaplan-Meier curve for overall survival by age subgroup, aged 70 to 75 years4

KM Curve: 70-75 years

Median overall survival (95% CI):

VYXEOS: 8.9 months (4.7, 12.2) (n=48/57)

7+3: 5.6 months (3.3, 7.5) (n=54/54)

Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.

Age was prospectively stratified in the initial analysis of the Phase 3 trial2

See full study design

See the Phase 3 Study Safety Profile

Limitations of subanalysis

  • This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS can be drawn from this analysis
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Strive for higher remission rates in sAML with VYXEOS1,3

In the Phase 3 trial, almost half of sAML patients treated with VYXEOS achieved CR+CRi3

Percentage of sAML patients who achieved CR and CR+CRi1,3

Overall response rate with VYXEOS treatment

CR, n/N:
VYXEOS: 58/153
7+3: 41/156
2-sided P=0.0361

CR+CRi, n/N:
VYXEOS: 73/153
7+3: 52/156
2-sided P=0.0163

See full study design

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Exploratory post hoc analysis

At 5 years, median overall survival was longer in patients who achieved CR or CRi with VYXEOS vs 7+34

5-YEAR FOLLOW-UP

Kaplan-Meier curve for overall survival in patients who achieved CR or CRi4

KM Curve

Median overall survival (95% CI):

VYXEOS: 21.7 months (13.0, 29.7) (n=50/73)

7+3: 10.4 months (7.8, 15.2) (n=43/52)

Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.

Limitations of subanalysis

  • This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS can be drawn from this analysis
  • Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=125)2,4
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics

See full study design

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For sAML patients whose treatment goals align with transplant, start with VYXEOS2

Data from the Phase 3 trial showed that more sAML patients reached HSCT with VYXEOS vs 7+32

Overall rate of HSCT2,c,d

Overall rate of HSCT for treatment with VYXEOS
 
 
First CR, induction failure, or as salvage after relapse.1
In the primary analysis of the Phase 3 trial, the overall rate of HSCT (first CR, induction failure, or as salvage after relapse) was 34% (52/153) in the VYXEOS arm and 25% (39/156) in the control arm.1

A greater proportion of sAML patients who achieved first CR with VYXEOS subsequently underwent HSCT vs 7+35

Rate of HSCT during first CR1,3,5,e

Rate of HSCT during first CR with VYXEOS

‌eFirst CR after 1 or 2 induction cycles.5

The foundation of sAML treatment is chemotherapy, with the ultimate goal of achieving remission and reaching HSCT6-8,f

 
 
 
 
 
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

See full study design

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Exploratory post hoc analysis

Long-term OS in patients who received HSCT in the Phase 3 trial2

LONG-TERM FOLLOW-UP

Analysis 1: Kaplan-Meier curve for overall survival landmarked from time of HSCT2

OS from time of HSCT after treatment with VYXEOS

Median overall survival (95% CI):

VYXEOS: Not reached (16.2, NR) (n=23/53)9

7+3: 10.3 months (6.2, 16.7) (n=30/39)9

Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.

5-year KM estimates from date of HSCT were not available, as the follow-up time from date of HSCT was less than 5 years2

KM-estimated survival rates from date of randomization were higher for VYXEOS vs 7+3 at 3 and 5 years and was >50% at 5 years for patients treated with VYXEOS10,11

Limitations of subanalysis

  • This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS following HSCT can be drawn from this analysis
  • Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=92)2
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
    • A higher proportion of patients proceeding to HSCT in the VYXEOS arm (75%) were in CR/CRi as compared with the 7+3 arm (62%)2
    • To address this limitation, Analysis 2 (right)(below) evaluated only those patients in each treatment arm who were in CR/CRi at the time they received HSCT4

Analysis 2: Kaplan-Meier curve for overall survival landmarked from time of HSCT in patients who achieved CR or CRi4

OS in from time of HSCT in CR/CRi patients who received VYXEOS

Median overall survival (95% CI):

VYXEOS: Not reached (15.6, NR) (n=19/41)

7+3: 11.7 months (4.6, 24.3) (n=17/24)

Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.

5-year KM estimates from date of HSCT were not available, as the follow-up time from date of HSCT was less than 5 years2

Limitations of subanalysis

  • This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS following HSCT after CR or CRi can be drawn from this analysis
  • Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=65)2,4
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics

See full study design

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Exploratory post hoc analysis

Patients who achieved CR or CRi and did not undergo transplant in the Phase 3 trial12,g

Median OS for non-HSCT
patients who achieved CR12

non-HSCT CR

Median OS for non-HSCT
patients who achieved CR+CRi12

non-HSCT CR+CRi

Limitations of subanalysis

  • This subgroup analysis was exploratory and not powered to determine statistical significance. No efficacy conclusions about OS following CR or CRi can be drawn from this analysis
  • Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=61)12
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics

gBased on primary analysis of median follow-up of 20.7 months.3

See full study design

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Study Design1,2

The Phase 3 study was a randomized, multicenter, open-label, active-controlled superiority study of VYXEOS (N=153) versus cytarabine and daunorubicin (7+3; N=156) in patients 60 to 75 years of age with newly-diagnosed t-AML or AML-MRC (N=309). Efficacy was established on the basis of overall survival from the date of randomization to death from any cause.1

VYXEOS 44 mg/100 mg per m2 (daunorubicin/cytarabine) was given intravenously on Days 1, 3, and 5 for first induction and on Days 1 and 3 for those needing a second induction. For consolidation, the VYXEOS dose was 29 mg/65 mg per m2 (daunorubicin/cytarabine) on Days 1 and 3. In the 7+3 arm, first induction was cytarabine 100 mg/m2/day on Days 1-7 by continuous infusion + daunorubicin 60 mg/m2/day on Days 1-3. For second induction and consolidation, cytarabine was dosed on Days 1-5 and daunorubicin on Days 1 and 2. Patients could receive up to 2 cycles of induction and 2 cycles of consolidation in each arm. Subsequent induction was highly recommended for patients who did not achieve a response and was mandatory for patients achieving >50% reduction in percent blasts.1

The prospectively planned overall survival analysis of the ITT population was conducted based on the final 5-year follow-up results from the Phase 3 trial. Exploratory post hoc subgroup analyses were also conducted.2

Learn more about the Phase 3 study design

INDICATION

VYXEOS is indicated for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t‑AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.

IMPORTANT SAFETY INFORMATION

WARNING: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-CONTAINING PRODUCTS

VYXEOS has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors.

Contraindications

VYXEOS is contraindicated in patients with a history of serious hypersensitivity reactions to cytarabine, daunorubicin, or any component of the formulation.

Warnings and Precautions

Hemorrhage

Serious or fatal hemorrhage events, including fatal CNS hemorrhages, associated with prolonged thrombocytopenia, have occurred with VYXEOS. The overall incidence (grade 1-5) of hemorrhagic events was 74% in the VYXEOS arm and 56% in the control arm. The most frequently reported hemorrhagic event was epistaxis (36% in VYXEOS arm and 18% in control arm). Grade 3 or greater events occurred in 12% of VYXEOS-treated patients and in 8% of patients in the control arm. Fatal treatment-emergent CNS hemorrhage not in the setting of progressive disease occurred in 2% of patients in the VYXEOS arm and in 0.7% of patients in the control arm. Monitor blood counts regularly and administer platelet transfusion support as required.

Cardiotoxicity

VYXEOS contains daunorubicin, which has a known risk of cardiotoxicity. This risk may be increased in patients with prior anthracycline therapy, preexisting cardiac disease, previous radiotherapy to the mediastinum, or concomitant use of cardiotoxic drugs. Assess cardiac function prior to VYXEOS treatment and repeat prior to consolidation and as clinically required. Discontinue VYXEOS in patients with impaired cardiac function unless the benefit of initiating or continuing treatment outweighs the risk. VYXEOS is not recommended in patients with cardiac function that is less than normal.

Total cumulative doses of non-liposomal daunorubicin greater than 550 mg/m2 have been associated with an increased incidence of drug-induced congestive heart failure. The tolerable limit appears lower (400 mg/m2) in patients who received radiation therapy to the mediastinum. Calculate the lifetime cumulative anthracycline exposure prior to each cycle of VYXEOS. VYXEOS is not recommended in patients whose lifetime anthracycline exposure has reached the maximum cumulative limit.

Hypersensitivity Reactions

Serious or fatal hypersensitivity reactions, including anaphylactic reactions, have been reported with daunorubicin and cytarabine. Monitor patients for hypersensitivity reactions. If a mild or moderate hypersensitivity reaction occurs, interrupt or slow the rate of infusion with VYXEOS and manage symptoms. If a severe or life-threatening hypersensitivity reaction occurs, discontinue VYXEOS permanently, treat the symptoms, and monitor until symptoms resolve.

Copper Overload

VYXEOS contains copper. Consult with a hepatologist and nephrologist with expertise in managing acute copper toxicity in patients with Wilson’s disease treated with VYXEOS. Monitor total serum copper, serum non-ceruloplasmin-bound copper, 24-hour urine copper levels, and serial neuropsychological examinations during VYXEOS treatment in patients with Wilson’s disease or other copper-related metabolic disorders. Use only if the benefits outweigh the risks. Discontinue in patients with signs or symptoms of acute copper toxicity.

Tissue Necrosis

Daunorubicin has been associated with severe local tissue necrosis at the site of drug extravasation. Administer VYXEOS by the intravenous route only. Confirm patency of intravenous access before administration. Do not administer by intramuscular or subcutaneous route.

Embryo-Fetal Toxicity

VYXEOS can cause embryo-fetal harm when administered to a pregnant woman. Patients should avoid becoming pregnant while taking VYXEOS. If VYXEOS is used during pregnancy or if the patient becomes pregnant while taking VYXEOS, apprise the patient of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of VYXEOS.

MOST COMMON ADVERSE REACTIONS

The most common adverse reactions (incidence ≥25%) are hemorrhagic events (74%), febrile neutropenia (70%), rash (56%), edema (55%), nausea (49%), mucositis (48%), diarrhea (48%), constipation (42%), musculoskeletal pain (43%), fatigue (39%), abdominal pain (36%), dyspnea (36%), headache (35%), cough (35%), decreased appetite (33%), arrhythmia (31%), pneumonia (31%), bacteremia (29%), chills (27%), sleep disorders (26%), and vomiting (25%).

Please see full Prescribing Information, including BOXED Warning.

AML=acute myeloid leukemia; CI=confidence interval; CR=complete remission; CRi=complete remission with incomplete neutrophil or platelet recovery; HR=hazard ratio; HSCT=hematopoietic stem cell transplant; ITT=intent to treat; KM=Kaplan-Meier; NCCN=National Comprehensive Cancer Network; NR=not reached; OS=overall survival; sAML=secondary AML; t-AML=therapy-related AML.

References: 1. VYXEOS [package insert]. Palo Alto, CA: Jazz Pharmaceuticals. 2. Lancet JE, Uy GL, Newell LF, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491. 3. Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018;36(26):2684-2692. 4. Supplement to: Lancet JE, Uy GL, Newell LF, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491. 5. Lin TL, Medeiros BC, Uy GL, et al. Outcomes by number of induction cycles with CPX-351 vs 7+3 chemotherapy in older adults with newly diagnosed high-risk/secondary acute myeloid leukemia (sAML). Presented at: American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL. Poster 7040. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.2.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed June 14, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. 7. Wang ES. Treating acute myeloid leukemia in older adults. Hematology Am Soc Hematol Educ Program. 2014;2014(1):14-20. 8. Lipof JJ, Loh KP, O’Dwyer K, et al. Allogeneic hematopoietic cell transplantation for older adults with acute myeloid leukemia. Cancers (Basel). 2018;10(6):179. 9. Data on File (VYX-2021-045). Jazz Pharmaceuticals, Inc. 10. Data on File (VYX-2021-046). Jazz Pharmaceuticals, Inc. 11.  Uy GL, Newell LF, Lin TL, et al. Transplant outcomes after CPX-351 vs 7+3 in older adults with newly diagnosed high-risk and/or secondary AML. Blood Adv. 2022. doi:10.1182/bloodadvances.2021006468 12.  Lin TL, Rizzieri DA, Ryan DH, et al. Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351: phase 3 post hoc analyses. Blood Adv. 2021;5(6):1719-1728.

INDICATION

VYXEOS is indicated for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t‑AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.

Important Safety Information

WARNING: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-CONTAINING PRODUCTS

VYXEOS has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors.