VYXEOS LIPOSOMAL IN AML-MRC AND t-AML PATIENTS:

RESULTS FROM EVERYDAY PRACTICE IN FRANCE AND ITALY WERE SIMILAR TO THOSE IN STUDY 3011–3

The French experience

103 patients with a median age of 67 (20–83) from 12 centres were diagnosed with AML-MRC or t-AML and treated with Vyxeos Liposomal. Median follow-up was 8.6 months.1

The French RWE - Patient Baseline Characteristics (N=103)1

n (%)
Age, years
Median (range)67 (20-83)
18-6021 (20)
>6082 (80)
Sex
Male54 (52)
Female49 (48)
AML subtype
AML-MRC74 (72)
MDS-AML35 (47)
CMML-AML9 (12)
t-AML27 (26)
Other*2 (2)
WBCs, median (range), x109/L3 (0.156)
Hyperleukocytosis9 (9)
Cytopenia97 (94)
125 (24)
241 (40)
331 (30)
Karyotype
Complex35 (34)
Monosomal28 (27)
Prior HMA18 (18)
2017 ELN genetic risk stratification (n=102)
Favourable2 (2)
Intermediate38 (37)
Adverse62 (61)
Lindsley's classifier (n=80)
de novo/pan-AML21 (26)
Secondary-type mutations AML37 (46)
TP53-mutated AML22 (28)

Adapted from Chiche et al. 2021

Values present n (%) of patients unless otherwise indicated

* Two patients were treated after myeloproliferative neoplasm AML (one with prior essential thombocythemia and one with myelofibrosis secondary to essential thombocythemia)

Vyxeos Liposomal efficacy in the French cohort:

Induction results1

59% ORR(61/103)

MRD negativity1

57%

of patients were MRD negative (16/28)

  • MRD <10-3 was evaluable in 28 of the 61 patients who achieved CR/CRi

Vyxeos Liposomal overcame the poor response rate associated with the ASXL1 and RUNX1 mutations1

16 months mOS1

  • 35% (36/103) of patients had an ASCT1
  • The majority of patients who were eligible and received Vyxeos Liposomal did not proceed to ASCT1

The Italian experience

71 patients with a median age of 66 (52-79) from 31 centres were diagnosed with s-AML and treated with Vyxeos Liposomal. Median follow-up was 11 months.2

The Italian RWE - Patient Baseline Characteristics (N=71)2

n (%)
Age, years
<7051 (71.8)
>7020 (28.2)
Sex
Male39 (54.9)
Female32 (45.1)
WBC
<30 × 109/L60 (84.5)
>30 × 109/L11 (15.5)
Marrow blasts
<30%22 (31.0)
>30%49 (69.0)
Previous HMA
No54 (76.1)
Yes17 (23.9)
NPM1 (evaluated in 68/71, 96%)
Wild type63 (92.7)
Mutated5 (7.3)
FLT3-ITD (evaluated in 69/71, 97%)
Negative64 (92.8)
Positive5 (7.2)
TP53 (evaluated in 37/71, 52%)
Wild type24 (64.9)
Mutated13 (35.1)
Karyotype
Favourable3 (4.7)
Intermediate36 (50.2)
Poor32 (45.1)
Vyxeos Liposomal indication
s-AML36 (50.2)
t-AML22 (31.0)
MDS-related changes13 (18.8)
ELN 2017
Low/intermediate8 (11.3)
Intermediate24 (33.8)
High39 (54.9)

Adapted from Guolo et al. 2020

Vyxeos Liposomal efficacy in the Italian cohort:

Induction results2

73% ORR(52/71)

MRD negativity2

~50%

of analysed patients achieved MRD negativity

  • Depth of response was evaluated after the first induction*
  • MRD was evaluated through flow cytometry in 40 patients and WT1-MRD analysis in 38 patients

The presence of TP53 mutation in the context of a complex karyotype did not impact the survival rate2

69% OS at 12 months2

  • 71% OS for non-HSCT patients at 12 months2
  • 100% OS for HSCT patients at 12-months2
    • 40% (20/50) of the patients who achieved CR received an HSCT2
See the efficacy of Vyxeos Liposomal from Study 301, and the French and Italian RWE studies

Vyxeos Lipsosomal Efficacy at a Glance

French RWE1Italian RWE2Study 3013,4
Vyxeos
Liposomal		DA 3+7
Median OS, months16.1NR
68.6% at 12 months		9.66.0
(p=0.003)
CR, n/N (%)57/103 (55)38/71 (54)3726
(p=0.04)
CR+CRi, n/N (%)*61/103 (59)52/71 (73)4833
(p=0.016)
MRD negativity, n/N (%)16/28 (57)~50%†NA

* Following induction
† Flow cytometry-based MRD assessment data were available from 17/31 centres (54.8%) for 40/71 patients (56.3%) and the MRD negativity rate was 37.5% (15/40 patients). WT1-based MRD was available for 15/31 (48.4%) centres for 38/71 patients (53.5%) and the MRD negativity rate was 53.8% (21/38 patients)

The French cohort study confirmed the acceptable safety profile reported in Study 3011
  • 60-day mortality was 8%
  • Median time to neutrophil recovery after the first induction was 29 days
  • Median time to platelet recovery after the first induction was 28 days

The French RWE – AEs Occurring During Vyxeos Liposomal Therapy Regardless of Causality Tolerability profile1

All grades, n/103 (%)Grade >3, n/103 (%)
Sepsis-101 (98)
Febrile neutropenia94 (91)94 (91)
Pneumonia37 (36)30 (30)
Bacteraemia-25 (24)
Invasive pulmonary aspergillosis-10 (10)
Bleeding12 (12)6 (6)
Epistaxis4 (4)0
Oral haemorrhage2 (2)1 (1)
Gastrointestinal haemorrhage1 (1)1 (1)
Intra-alveolar haemorrhage1 (1)1 (1)
Intracranial haemorrhage2 (2)0
Haematuria1 (1)1 (1)
Ocular haemorrhage1 (1)0
Hypertensive crisis10 (10)2 (2)
Heart failure9 (9)7 (7)
Gastrointestinal toxicity52 (50)4 (4)
Nausea37 (36)0
Vomiting13 (13)1 (1)
Diarrhoea7 (7)0
Mucositis23 (22)3 (3)
Rash26 (25)2 (2)
Alopecia11 (11)0

Adapted from Chiche et al. 2021

Most AEs were easily manageable and resolved completely within the Italian cohort2
  • 60-day mortality was 7%
  • Median time to neutrophil recovery after the first induction was 38 days
  • Median time to platelet recovery after the first induction was 28 days

The Italian RWE – Grade ≥1 AEs Occurring During Therapy2

Induction, n/71 (%)Second cycle, n/39 (%)
All grade AEs57 (80.3)25 (64.1)
Fever of unknown origin20 (28)9 (23.7)
Sepsis20 (28)3 (7.7)
Pneumonia8 (11.3)3 (7.7)
Pneumocystis jirovecii-related pneumonia2 (2.8)1 (2.6)
Invasive fungal infections3 (4.2)-
Mucositis5 (7)2 (5.2)
Skin- rash (self-resolving)18 (25.4)8 (20.5)
Alopecia4 (5.6)-

Adapted from Guolo et al. 2020

See the safety of Vyxeos Liposomal from Study 301, and French and Italian RWE studies

Vyxeos Liposomal Tolerability at a Glance

French RWE1Italian RWE2Study 3013,4
Vyxeos LiposomalDA 3+7
60-day mortality, %8713.721.2
(p=0.097)
Neutrophil recovery, days29383529
Platelet recovery, days28283729

Two RWE studies have confirmed the efficacy and safety of Vyxeos Liposomal, as shown in Study 3011–4

Peer-reviewed evidence has so far demonstrated that:1-3

  • Vyxeos Liposomal can deliver efficacy, even in those with poor prognostic factors (eg, a complex karyotype)
  • Vyxeos Liposomal can lay the foundation towards long-term survival for patients that receive transplant
Visit the Resource Centre for exclusive access to reprints of the RWE and 5-year analysis papers
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In AML-MRC and t-AML, consider Vyxeos Liposomal first.

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FOOTNOTES

* MRD assessment was not a mandatory endpoint of the study. It was performed according to internal clinical practice, following ELN suggestions. WT1-MRD assessment was performed as recommended by ELN. Flow cytometry-based MRD assessment data were available from 17/31 centres (54.8%) for 40/71 patients (56.3%) and the MRD negativity rate was 37.5% (15/40 patients). WT1-based MRD was available for 15/31 (48.4%) centres for 38/71 patients (53.5%) and the MRD-negativity rate was 53.8% (21/38 patients)

ABBREVIATIONS

AE, adverse event; AML-MRC, acute myeloid leukaemia with myelodysplasia-related changes; ASCT, allogeneic stem cell transplant; ASXL1, additional sex comb-like 1; CMML, chronic myelomonocytic leukaemia; CR, complete remission; CRi, complete remission with incomplete platelet and neutrophil recovery; DA, daunorubicin + cytarabine; ELN, European LeukemiaNet; FLT3-ITD, FMS-like tyrosine kinase-3 internal tandem duplication; HMA, hypomethylating agent; HSCT, haematopoietic stem cell transplant; MDS, myelodysplastic syndrome; mOS, median overall survival; MRD, minimal residual disease; NA, not applicable; NPM1, nucleophosmin 1; NR, not reached; ORR, overall response rate; OS, overall survival; PR, partial response; RCT, randomised control trial; RUNX1, runt-related transcription factor 1; RWE, real-world evidence; s-AML, secondary acute myeloid leukaemia; t-AML, therapy-related acute myeloid leukaemia; TP53, tumour protein p53; WBC, white blood cell; WT1-MRD, Wilms' tumour 1 minimal residual disease

REFERENCES
  1. Chiche E, et al. Blood Adv 2021;5(1):176–184
  2. Guolo F, et al. Blood Cancer J 2020;10(10):96
  3. Lancet JE, et al. Lancet Haematol 2021;8(7):e481–e491
  4. Lancet JE, et al. J Clin Oncol 2018;36(26):2684–2692
  5. Kolitz JE, et al. Leuk Lymphoma 2020;61(3):631–640

ADVERSE EVENTS REPORTING

Adverse events should be reported. Reporting forms and information for the UK can be found at https://yellowcard.mhra.gov.uk/

For Ireland, reporting forms and information can be found at: www.hpra.ie

Adverse events should also be reported to Jazz Pharmaceuticals at AEreporting@jazzpharma.com

UK-VYX-2100196 | September 2021