Vyxeos^® Liposomal in AML-MRC and t-AML Patients:

Results From Everyday Practice in Four European Cohorts Were Similar to Those in Study 301^1–5

England
France

Italy
Germany

The English experience

211 patients with a medican age of 65 (IQR 59–70) were diagnosed with AML-MRC, t-AML, or antecedent MDS or CMML and treated with Vyxeos Liposomal. Median follow-up was 20.7 months.¹

England RWE - Patient Baseline Characteristics (N=211)¹

	All patients (N=211)	Aged <60 years (n=60)	Aged ≥60 years (n=151)
Age at diagnosis, years
Mean (SD)	62.7 (10.3)	50.0 (10.2)	67.8 (4.3)
Median (IQR)	65 (59,70)	53 (46, 58)	68 (64, 70)
Age group, n (%)
18 to 44 years	12 (6)	12 (20)	-
45 to 59 years	48 (23)	48 (80)	-
60 to 69 years	97 (46)	-	97 (64)
≥70 years	54 (26)	-	54 (36)
Sex, n (%)
Male	133 (63)	33 (55)	100 (66)
Female	78 (37)	27 (45)	51 (34)
AML subtype, n (%)
Unspecified de novo AML*	91 (43)	30 (50)	61 (40)
Secondary AML	87 (41)	21 (35)	66 (44)
AML-MRC (ICD-0-3 code)	33 (16)	9 (15)	24 (16)

*Likely unspecified de novo AML-MRC (cytogenetic status unknown)

Vyxeos Liposomal efficacy in the English cohort:

All patients¹

Age Stratified¹

HSCT Recipients¹

Post-HSCT¹

Post-HSCT Stratified by Age¹

Select a graph to view above

All patients¹

Age Stratified¹

HSCT Recipients¹

Post-HSCT¹

Post-HSCT Stratified by Age¹

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.²

France RWE - Patient Baseline Characteristics (N=103)²

	n (%)
Age, years
Median (range)	67 (20-83)
18-60	21 (20)
>60	82 (80)
Sex
Male	54 (52)
Female	49 (48)
AML subtype
AML-MRC	74 (72)
MDS-AML	35 (47)
CMML-AML	9 (12)
t-AML	27 (26)
Other*	2 (2)
WBCs, median (range), x10⁹/L	3 (0–156)
Hyperleukocytosis	9 (9)
Cytopenia	97 (94)
1	25 (24)
2	41 (40)
3	31 (30)
Karyotype
Complex	35 (34)
Monosomal	28 (27)
Prior HMA	18 (18)
2017 ELN genetic risk stratification (n=102)
Favourable	2 (2)
Intermediate	38 (37)
Adverse	62 (61)
Lindsley's classifier (n=80)
de novo/pan-AML	21 (26)
Secondary-type mutations AML	37 (46)
TP53-mutated AML	22 (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 thrombocythemia and one with myelofibrosis secondary to essential thrombocythemia)

Vyxeos Liposomal efficacy in the French cohort:

Induction results²

59% ORR(61/103)

MRD negativity²

57%

of patients were MRD negative (16/28)

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

16 months mOS²

35% (36/103) of patients had an ASCT²
The majority of patients who were eligible and received Vyxeos Liposomal did not proceed to ASCT²

Vyxeos Liposomal overcame the poor response rate associated with the ASXL1 and RUNX1 mutations²

Italy
Germany

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.³

Italy RWE - Patient Baseline Characteristics (N=71)³

	n (%)
Age, years
<70	51 (71.8)
>70	20 (28.2)
Sex
Male	39 (54.9)
Female	32 (45.1)
WBC
<30 × 10⁹/L	60 (84.5)
>30 × 10⁹/L	11 (15.5)
Marrow blasts
<30%	22 (31.0)
>30%	49 (69.0)
Previous HMA
No	54 (76.1)
Yes	17 (23.9)
NPM1 (evaluated in 68/71, 96%)
Wild type	63 (92.7)
Mutated	5 (7.3)
FLT3-ITD (evaluated in 69/71, 97%)
Negative	64 (92.8)
Positive	5 (7.2)
TP53 (evaluated in 37/71, 52%)
Wild type	24 (64.9)
Mutated	13 (35.1)
Karyotype
Favourable	3 (4.7)
Intermediate	36 (50.2)
Poor	32 (45.1)
Vyxeos Liposomal indication
s-AML	36 (50.2)
t-AML	22 (31.0)
MDS-related changes	13 (18.8)
ELN 2017
Low/intermediate	8 (11.3)
Intermediate	24 (33.8)
High	39 (54.9)

Adapted from Guolo et al. 2020

Vyxeos Liposomal efficacy in the Italian cohort:

Induction results³

73% ORR(52/71)

MRD negativity³

~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

69% OS at 12 months³

71% OS for non-HSCT patients at 12 months³
100% OS for HSCT patients at 12 months³
- 40% (20/50) of the patients who achieved CR received an HSCT³

The presence of TP53 mutation in the context of a complex karyotype did not impact the survival rate³

The German experience

188 patients with a median age of 65 (range 26–80) across 25 centres were diagnosed with AML-MRC or t-AML and treated with Vyxeos Liposomal. Median follow-up was 9.3 months.⁴

Germany RWE - Patient Baseline Characteristics (N=188)⁴

Characteristics	n	%
Age, years (median,range)	65 (26-80)
Gender
Female	70	37
Male	118	63
Karnofsky (n=165)
≥80	135	82
<80	30	18
HCT-CI (n=155)
Low	29	18
Intermediate	55	35
High	74	47
AML subtype (n=186)
AML-MRC	131	70
t-AML	53	29
Other*	2	1
2017 ELN genetic risk (n=179)
Favourable	12	7
Intermediate	59	33
Adverse	108	60
Karyotype (n=179)
Normal	63	35
Abnormal	116	65
Complex	44	25
Non-complex	72	40
Molecular genetics
NPM1/n.d.	18/11	10/6
FLT3-ITD/n.d.	13/13	7/7
ASXL1/n.d.	31/24	16/13
TP53/n.d.	14/26	7/14
RUNX1/n.d.	24/20	13/11
BM blast count at diagnosis (median, range)	38 (7-99)
PB blast count at diagnosis (median, range)	10 (0-92)
WBC at diagnosis, ×10³/μl (median, range)	3.8 (0.6/330)
Pretreatment with HMA	19	10

Adapted from Rautenberg et al. 2021

* Secondary AML evolving from systemic mastocytosis (n=1) and blastic plasmacytoid dendric cell neoplasm with antecedent history of chronic myelomonocytic leukaemia

Vyxeos Liposomal efficacy in the German cohort:

Induction results⁴

67% ORRpost induction(120/179)

MRD negativity⁴

64%

of patients achieved MRD negativity <10^-3 (23/36) via flow cytometry analysis

MRD status was available for 36 of the 85 patients (42%) who achieved CR/CRi

21 months mOS⁴

62% (116/188) patients underwent HSCT⁴
An estimated 73% of all HSCT patients reached 2-year survival⁴
82 patients went on to receive allo-HSCT without further therapy⁴
- 34 patients underwent bridging therapy consisting of Vyxeos Liposomal and/or cytarabine consolidation, HMA or salvage therapy before receiving allo-HSCT⁴

54% (14/26) of patients with TP53^mut achieved CR/CRi with Vyxeos Liposomal^4,6

See the efficacy of Vyxeos Liposomal from Study 301
and the European RWE studies

Vyxeos Liposomal Efficacy at a Glance

	Study 301^5,6		England¹ (N=211)	France² (N=103)	Italy³ (N=71)	Germany⁴ (N=188)
	Vyxeos Liposomal (N=153)	DA 3+7 (N=156)	England¹ (N=211)	France² (N=103)	Italy³ (N=71)	Germany⁴ (N=188)
Median OS, months	9.6	6.0	12.9	16.1	NR (68.6% at 12 months)	21
Median OS, months	(p=0.009)		12.9	16.1	NR (68.6% at 12 months)	21
Median OS post-HSCT, months	NR	10.25	NR (72% at 12 months)	NR	NR (100% at 12 months)	NR (73% at 12 months)
Median OS post-HSCT, months	(p=0.009)		NR (72% at 12 months)	NR	NR (100% at 12 months)	NR (73% at 12 months)
CR, n/N (%)	37%	26%	NA	57/103 (55)	38/71 (54)	NA
CR, n/N (%)	(p=0.04)		NA	57/103 (55)	38/71 (54)	NA
CR+CRi, n/N (%)*	48%	33%	NA	61/103 (59)	46/71 (65)	85/179 (47)
CR+CRi, n/N (%)*	(p=0.016)		NA	61/103 (59)	46/71 (65)	85/179 (47)
CR+CRi+PR, n/N (%)*	NA		NA	NA	52/71 (73)	NA
MRD negativity, n/N (%)*	NA		NA	16/28 (57)	~50%^†	23/36 (64)

* 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)

Safety results were not reported for the English cohort as the NCRAS database did not contain the relevant information

The French cohort study confirmed the acceptable safety profile reported in Study 301²

Median time to neutrophil recovery after the first induction was 29 days
Median time to platelet recovery after the first induction was 28 days

France RWE – AEs Occurring During Vyxeos Liposomal Therapy Regardless of Causality Tolerability profile²

	All grades	Grade ≥3
Sepsis*	-	101 (98)
Febrile neutropenia	94 (91)	94 (91)
Pneumonia	37 (36)	30 (30)
Bacteraemia	-	25 (24)
Invasive pulmonary aspergillosis	-	10 (10)
Bleeding	12 (12)	6 (6)
Epistaxis	4 (4)	0
Oral haemorrhage	2 (2)	1 (1)
Gastrointestinal haemorrhage	1 (1)	1 (1)
Intra-alveolar haemorrhage	1 (1)	1 (1)
Intracranial haemorrhage	2 (2)	0
Haematuria	1 (1)	1 (1)
Ocular haemorrhage	1 (1)	0
Hypertensive crisis	10 (10)	2 (2)
Heart failure	9 (9)	7 (7)
Gastrointestinal toxicity	52 (50)	4 (4)
Nausea	37 (36)	0
Vomiting	13 (13)	1 (1)
Diarrhoea	7 (7)	0
Mucositis	23 (22)	3 (3)
Rash	26 (25)	2 (2)
Alopecia	11 (11)	0

* Sepsis was defined by either the CTCAE criteria (Grade >3 sepsis is a positive blood culture with signs and symptoms indicating treatment initiation) or the SIRS criteria (>2 of the following - temperature <36°C or >38°C; heart rate >90 beats/minute; respiratory rate >20 breaths/minute or ppCO₂ <32 mmHg; WBC >12,000/mm³ or the presence of >10% immature neutrophils).

Values represent n (%) of patients.

Adapted from Chiche et al. 2021

Most AEs were easily manageable and resolved completely within the Italian cohort³

Median time to neutrophil recovery after the first induction was 38 days
Median time to platelet recovery after the first induction was 28 days

Italy RWE – Grade ≥1 AEs Occurring During Therapy³

	Induction, n/71 (%)	Second cycle, n/39 (%)
All grade AEs	57 (80.3)	25 (64.1)
Fever of unknown origin	20 (28)	9 (23.7)
Sepsis	20 (28)	3 (7.7)
Pneumonia	8 (11.3)	3 (7.7)
Pneumocystis jirovecii-related pneumonia	2 (2.8)	1 (2.6)
Invasive fungal infections	3 (4.2)	-
Mucositis	5 (7)	2 (5.2)
Skin- rash (self-resolving)	18 (25.4)	8 (20.5)
Alopecia	4 (5.6)	-

Adapted from Guolo et al. 2020

The German RWE study demonstrated a similar safety profile to the French and Italian studies⁴

Median time to neutrophil recovery after the first induction was 33 days
Median time to platelet recovery after the first induction was 30 days

Germany RWE – Grade ≥3 treatment toxicities⁴

Characteristics	n	%
Grade III/IV non-hemarologic tocicities (n = 188)
Infection	41	22
GI (mucositis, nausea, vomiting)	7	4
Bleeding	7	4
Renal failure	5	3
Febrile neutropenia	28	15
Pneumonia	42	22
Mortality on Day 30 after Vyxeos Liposomal unduction (n = 176)*
Alive	162	92
Dead	14	8

Adapted from Rautenberg et al. 2021

* Patients proceeding to allo-HSCT before Day 30 following induction with Vyxeos Liposomal have been excluded

See the safety of Vyxeos Liposomal from Study 301
and the European RWE studies

Vyxeos Liposomal Safety at a Glance

	Study 301⁵		England¹ (N=211)	France² (N=103)	Italy³ (N=71)	Germany⁴ (N=188)
	Vyxeos Liposomal (N=153)	DA 3+7 (N=156)	England¹ (N=211)	France² (N=103)	Italy³ (N=71)	Germany⁴ (N=188)
Neutrophil recovery, days	35	29	NA	29	38	33
Platelet recovery, days	37	29	NA	28	28	30

Vyxeos Liposomal Study 301 results are now complemented by four European RWE studies in over 500 patients^1–5,7

Peer-reviewed evidence has so far demonstrated that:^1-7

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
Vyxeos Liposomal demonstrated an acceptable safety profile vs DA 3+7

Of note, the authors of the German study concluded:

A combined approach applying an effective induction with Vyxeos Liposomal and inducing an MRD-negative CR followed by the subsequent allo-HSCT without further delay may constitute the treatment approach with the highest probability of cure for patients with AML-MRC or t-AML.⁴

Visit the Resource Centre for exclusive access to reprints of the RWE and 5-year analysis papers

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FOOTNOTES

* To protect patient confidentiality, the NCRAS suppresses specific numbers <6

† 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)

‡ MLFS is defined as <5% blasts in the bone marrow showing no blasts with Auer rods and no extramedullary disease, does not require count recovery

ABBREVIATIONS

AE, adverse event; allo-HSCT, allogeneic haematopoietic stem cell transplant; AML, acute myeloid leukaemia; AML-MRC, acute myeloid leukaemia with myelodysplasia-related changes; ASCT, allogeneic stem cell transplant; ASXL1, additional sex comb-like 1; BM, bone marrow; CI, confidence interval; CMML, chronic myelomonocytic leukaemia; CR, complete remission; CRi, complete remission with incomplete platelet and neutrophil recovery; DA, daunorubicin + cytarabine; ECOG, Eastern Cooperative Oncology Group; EFS, event-free survival; ELN, European LeukemiaNet; FLT3-ITD, FMS-like tyrosine kinase 3 internal tandem duplication; GI, gastrointestinal; HES, hypereosinophilic syndrome; HMA, hypomethylating agent; HR, hazard ratio; HSCT, haematopoietic stem cell transplant; KM, Kaplan-Meier; MDS, myelodysplastic syndrome; MLFS, morphologic leukaemia-free state; mOS, median overall survival; MRD, minimal residual disease; NA, not applicable; NCRAS, National Cancer Registration and Analysis Service; n.d., not done; NE, not estimable; NR, not reached; ORR, overall response rate; OS, overall survival; PB, peripheral blood; PR, partial response; Q1, first quartile; Q3, third quartile; RCT, randomised control trial; RWE, real-world evidence; SACT, systemic anti-cancer therapy; s-AML, secondary acute myeloid leukaemia; SD, standard deviation; t-AML, therapy-related acute myeloid leukaemia; WBC, white blood cell; WT1-MRD, Wilms' tumour 1 minimal residual disease

REFERENCES

Legg A, et al. Abstract P513. EHA Annual Congress 2022
Chiche E, et al. Blood Adv 2021;5(1):176–184
Guolo F, et al. Blood Cancer J 2020;10(10):96
Rautenberg C, et al. Blood Cancer J 2021;11:164
Lancet JE, et al. J Clin Oncol 2018;36(26):2684–2692
Rautenberg C, et al. Blood Cancer J 2021;11:164 (Supplementary material)
Lancet JE, et al. Lancet Haematol 2021;8(7):e481–e491

Vyxeos® Liposomal in AML-MRC and t-AML Patients:

Results From Everyday Practice in Four European Cohorts Were Similar to Those in Study 3011–5

Vyxeos Liposomal delivers quadruple endpoint superiority vs DA 3+7 improving:5

Four European RWE studies complement these findings.1–4

The English experience

England RWE - Patient Baseline Characteristics (N=211)1

Vyxeos Liposomal efficacy in the English cohort:

All patients1

Age Stratified1

HSCT Recipients1

Post-HSCT1

Post-HSCT Stratified by Age1

Select a graph to view above

The French experience

France RWE - Patient Baseline Characteristics (N=103)2

Vyxeos Liposomal efficacy in the French cohort:

Induction results2

MRD negativity2

16 months mOS2

Vyxeos Liposomal overcame the poor response rate associated with the ASXL1 and RUNX1 mutations2

The Italian experience

Italy RWE - Patient Baseline Characteristics (N=71)3

Vyxeos Liposomal efficacy in the Italian cohort:

Induction results3

MRD negativity3

69% OS at 12 months3

The presence of TP53 mutation in the context of a complex karyotype did not impact the survival rate3

The German experience

Germany RWE - Patient Baseline Characteristics (N=188)4

Vyxeos Liposomal efficacy in the German cohort:

Induction results4

MRD negativity4

21 months mOS4

54% (14/26) of patients with TP53mut achieved CR/CRi with Vyxeos Liposomal4,6

Vyxeos Liposomal Efficacy at a Glance

France RWE – AEs Occurring During Vyxeos Liposomal Therapy Regardless of Causality Tolerability profile2

Italy RWE – Grade ≥1 AEs Occurring During Therapy3

Germany RWE – Grade ≥3 treatment toxicities4

Vyxeos Liposomal Safety at a Glance

Vyxeos Liposomal Study 301 results are now complemented by four European RWE studies in over 500 patients1–5,7

RELATED CONTENT

Watch UK AML experts give their views on the RWE of Vyxeos Liposomal from BSH ’22 with our interactive learning webpage

FOOTNOTES

ABBREVIATIONS

REFERENCES

Vyxeos^® Liposomal in AML-MRC and t-AML Patients:

Results From Everyday Practice in Four European Cohorts Were Similar to Those in Study 301^1–5

Vyxeos Liposomal delivers quadruple endpoint superiority vs DA 3+7
improving:⁵

Four European RWE studies complement these findings.^1–4

England RWE - Patient Baseline Characteristics (N=211)¹

All patients¹

Age Stratified¹

HSCT Recipients¹

Post-HSCT¹

Post-HSCT Stratified by Age¹

France RWE - Patient Baseline Characteristics (N=103)²

Induction results²

MRD negativity²

16 months mOS²

Vyxeos Liposomal overcame the poor response rate associated with the ASXL1 and RUNX1 mutations²

Italy RWE - Patient Baseline Characteristics (N=71)³

Induction results³

MRD negativity³

69% OS at 12 months³

The presence of TP53 mutation in the context of a complex karyotype did not impact the survival rate³

Germany RWE - Patient Baseline Characteristics (N=188)⁴

Induction results⁴

MRD negativity⁴

21 months mOS⁴

54% (14/26) of patients with TP53^mut achieved CR/CRi with Vyxeos Liposomal^4,6

France RWE – AEs Occurring During Vyxeos Liposomal Therapy Regardless of Causality Tolerability profile²

Italy RWE – Grade ≥1 AEs Occurring During Therapy³

Germany RWE – Grade ≥3 treatment toxicities⁴

Vyxeos Liposomal Study 301 results are now complemented by four European RWE studies in over 500 patients^1–5,7