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

Median overall survival (primary endpoint) of 9.6 months with VYXEOS vs 5.9 months with 7+3 (HR=0.69 [0.52, 0.90], P=0.005b)1

With median follow-up of 60 months, the improvement in OS was maintained with a stable hazard ratio2

New
5-Year Follow-Up

Kaplan-Meier curve for overall survival, ITT population2

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

aCytarabine 100 mg/m2 and daunorubicin 60 mg/m2.1

bP value is 2-sided.1

Strive for higher remission rates in sAML with VYXEOS1,3

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
P=0.036b

CR+CRi n/N:
VYXEOS: 73/153
7+3: 52/156
P=0.016b

‌bP value is 2-sided.1

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For sAML patients whose treatment goals align with transplant, start with VYXEOS1

More sAML patients received HSCT following treatment with VYXEOS vs 7+31

Overall rate of HSCT1,2,c,d

Overall rate of HSCT for treatment with VYXEOS
First CR, induction failure, or as salvage after relapse.1
At 5-year follow-up, HSCT had been received by 53/153 (35%) and 39/156 (25%) patients in the VYXEOS and 7+3 arms, respectively.2

A greater proportion of sAML patients who achieved first CR with VYXEOS subsequently underwent HSCT4

Rate of HSCT during first CR1,3,4,e

Rate of HSCT during first CR with VYXEOS

‌eFirst CR after 1 or 2 induction cycles.4

The goal of chemotherapy is to eliminate as many leukemia cells from the body as possible to achieve remission,5,6 and low leukemic burden impacts outcomes of HSCT7

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.

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Exploratory post hoc analysis of patients who achieved CR or CRi and did not undergo transplant in the Phase 3 trial8,f

Median OS for non-HSCT
patients who achieved CR8

Median OS for non-HSCT
patients who achieved CR+CRi8

Limitations of subanalysis8

  • 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)8
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics

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

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Exploratory post hoc analyses of 5-year OS in patients who received HSCT in the Phase 3 trial2

5-YEAR FOLLOW-UP

Analysis 1: Kaplan-Meier curve for overall survival landmarked from time of transplant, ITT population2

OS from time of HSCT after treatment with VYXEOS

Median survival (95% CI)

VYXEOS: Not reached (n=25/53)
7+3: 10.3 months (6.2, 16.7) (n=30/39)

Limitations of subanalysis2

  • This subgroup analysis was exploratory and 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 (77%) 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 HSCT2

Analysis 2: Kaplan-Meier curve for overall survival landmarked from time of transplant in patients who achieved CR or CRi2

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

Median survival (95% CI)

VYXEOS: Not reached (n=19/41)
7+3: 11.7 months (4.6, 24.3) (n=17/24)

Limitations of subanalysis2

  • This subgroup analysis was exploratory and 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
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
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Discussion of the pivotal Phase 3 trial

Dr. Bayard Powell, section chief of Hematology and Oncology at Wake Forest Baptist Health, reviews the VYXEOS Phase 3 trial in detail and explains what the efficacy and safety data mean for adult sAML patients

Results of the Phase 3 trial were also published in the Journal of Clinical Oncology3

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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

A preplanned overall survival analysis was conducted based on the final 5-year follow-up results from the Phase 3 trial.2

Learn more about the Phase 3 study design

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INDICATION

VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

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. 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%) were 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 recovery; HR=hazard ratio; HSCT=hematopoietic stem cell transplant; ITT=intent to treat; KM=Kaplan-Meier; NCCN=National Comprehensive Cancer Network; 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. Five-year final results of a phase 3 study of CPX-351 versus 7+3 in older adults with newly diagnosed high-risk/secondary AML. Presented at: American Society of Clinical Oncology ASCO20 Virtual Scientific Program; May 29-31, 2020. Poster 283. 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. 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. 5. Wang ES. Treating acute myeloid leukemia in older adults. Hematology Am Soc Hematol Educ Program. 2014;2014(1):14-20. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed December 23, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. 7. Zhou Y, Othus M, Araki D, et al. Pre- and post-transplant quantification of measurable (‘minimal’) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia. Leukemia. 2016;30(7):1456-1464. 8. Lin TL, Ryan RJ, Faderl S, et al. 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. Presented at: American Society of Clinical Oncology ASCO20 Virtual Scientific Program; May 29-31, 2020. Poster 310.

INDICATION

VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

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.