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Real-world evidence

Real-world evidence may complement the findings of randomized controlled trials.1 Results should be interpreted with caution as these are real-world evidence studies that are not powered to determine statistical significance; direct comparisons between real-world results and randomized controlled trials should be avoided

Real-world data: MRD

Real-world studies of VYXEOS examined rates of MRD negativity,2-4 a marker of deep remission5

MRD was not assessed in the Phase 3 study for VYXEOS, and its relevance as a predictor of OS remains a topic for further investigation.6

In real-world studies, up to 64% of patients treated with VYXEOS achieved MRD negativity following CR/CRi.2-4

MRD negativity rate in evaluable patients
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MRD assessment may occur after the completion of initial induction and before HSCT.7

Study Design & Safety
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    Retrospective chart review (N=188) of newly diagnosed patients median age 65 years (range: 26-89) with AML-MRC or t-AML treated with VYXEOS across 25 German centers between 2018 and 2020. Dosing was administered per the EU label.a Patient characteristics were similar to the Phase 3 study, but the treatment course substantially differed in that a much lower frequency (14%) received second induction with VYXEOS compared with 31% in the Phase 3 study. Of patients who achieved CR/CRi (n=85) after induction, 36 were tested for MRD at the time of transplant.

    Safety (n=188) was consistent with the Phase 3 study. Day 30 mortality after VYXEOS induction (n=176) was 8% (60-day mortality was not reported). Grade 3/4 nonhematologic toxicities included infection (22%), pneumonia (22%), febrile neutropenia (15%), gastrointestinal (4%), bleeding (4%), and renal failure (3%). In patients with CR/CRi, recovery to ANC ≥500/μl and platelet count ≥50,000/μl was observed in 95% and 92% of patients, respectively. Median time to ANC and platelet recovery was 33 days (range: 6-99 days) and 30 days (range: 7-77 days), respectively.

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    Retrospective chart review (N=103) of newly diagnosed, previously untreated adult patients diagnosed with AML-MRC or t-AML across 12 French centers treated with VYXEOS between April 2018 and November 2019. Patients received 1 or 2 induction cycles. There was one exception to the Phase 3 study: eligible patients were aged >18 years; however, the median age was 67 years (range: 20-83). Dosing was administered per the US/EU labels.a Baseline patient characteristics were similar to the Phase 3 study, with the exception of prior HMA exposure (18% vs 40.5% in the VYXEOS arm of the Phase 3 study) and age range (>18 years vs 60-75 years in the Phase 3 study). Of patients who achieved CR/CRi (n=61), 28 were tested for MRD at the time of first consolidation cycle.

    Safety (n=103) was consistent with the Phase 3 study. 30-day mortality was 6% and 60-day mortality was 8%. Adverse events during treatment regardless of causality reported as all grades and with a frequency of ≥10% included febrile neutropenia (91%), gastrointestinal toxicity (50%), pneumonia (36%), nausea (36%), rash (25%), mucositis (22%), vomiting (13%), bleeding (12%), alopecia (11%), and hypertensive crisis (10%). Neutrophil count and platelet count remained >0.5 x 109/L and 20 x 109L in only 1 patient and 2 patients, respectively. Median time to neutrophil recovery (>0.5 x 109/L) and platelet recovery (>20 x 109L) after the first induction was 29 days (range: 19-146 days) and 28 days (range: 12-77 days), respectively. Nine patients discontinued treatment due to prolonged hematological toxicity.

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    Retrospective chart review (N=71) across 31 centers in the Italian Compassionate Use Program for VYXEOS between June 2018 and July 2019. Patients median age 66 years (range: 52-79) had confirmed sAML or t-AML according to WHO 2016 criteria. Dosing was administered per the Phase 3 study.a Six patients (9%) presented with ECOG PS 3-4 upon enrollment. Among patients who achieved CR/CRi after first induction (n=46), 40 patients were assessed with MFC-MRD and 38 were tested with WT-1 based MRD assessment.

    Safety (n=71) was consistent with the Phase 3 study. 30-day mortality was 4.2% (n=3/71) and 60-day mortality was 7% (n=5/71). 80.3% of patients experienced > grade 1 adverse events during induction. Most adverse events were infections, including fever of unknown origin (28%), sepsis (28%), and pneumonia (11.3%). Others adverse events included mucositis (7%) and a self-resolving diffuse skin rash (25.4%). Median time to neutrophil recovery (>0.5 x109/L) and platelet recovery (>25 x109/L) was 38 days (range: 12-60 days) and 28 days (range: 12-60 days), respectively.


  • Results cannot be compared across studies as MRD assessment in AML lacks standardization with several technologies available for MRD assessment5
  • Results should be interpreted with caution as these are real-world evidence studies that are not powered to determine statistical significance
  • Direct comparisons between real-world evidence studies and randomized controlled trials are difficult8
  • ANC=absolute neutrophil count;
    MRD=minimal/measurable residual disease;
    t-AML=therapy-related acute myeloid leukemia;
    WHO=World Health Organization;
    WT1=Wilms tumor 1.
  • aDosing regimens in the US and EU labels are identical.9,10

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 Open Close


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.


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

Warnings and Precautions

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.


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.


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.

References: 1. Gyawali B, Parsad S, Feinberg BA, Nabhan C. Real-world evidence and randomized studies in the precision oncology era: the right balance. JCO Precis Oncol. 2017; doi: 10.1200/PO.17.00132.
2. Rautenberg C, Stölzel F, Röllig C, et al. Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia. Blood Cancer J. 2021;11(10):164. 3. Chiche E, Rahmé R, Bertoli S, et al. Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort. Blood Adv. 2021;5(1):176-184. 4. Guolo F, Fianchi L, Minetto P, et al. CPX-351 treatment in secondary acute myeloblastic leukemia is effective and improves the feasibility of allogeneic stem cell transplantation: results of the Italian compassionate use program. Blood Cancer J. 2020;10(10):96. 5. Cluzeau T, Lemoli RM, McCloskey J, Cooper T. Measurable residual disease in high-risk acute myeloid leukemia. Cancers (Basel). 2022;14(5):1278. 6. 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. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.2.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed April 3, 2024. To view the most recent and complete version of the guideline, go online to 8. Kim HS, Lee S, Kim JH. Real-world evidence versus randomized controlled trial: clinical research based on electronic medical records. J Korean Med Sci. 2018;33(34):e213. 9. Vyxeos Liposomal EU Summary of Product Characteristics. Jazz Pharmaceuticals, Inc. 10. VYXEOS [package insert]. Palo Alto, CA: Jazz Pharmaceuticals. 11. Lalayanni C, Gavriilaki E, Athanasiadou A, et al. Secondary acute myeloid leukemia (sAML): similarly dismal outcomes of AML after an antecedent hematologic disorder and therapy related AML. Clin Lymphoma Myeloma Leuk. 2022;22(4):e233-e240. 12. Capelli D, Menotti D, Florentini A, Sarcani F, Olivieri A. Chapter 7: Secondary acute myeloid leukemia: pathogenesis and treatment. Accessed March 21, 2024. /books /NBK586211 /?report=printable