Stakeholder Insight: Acute Leukemias - Reaching the limits of cytotoxic chemotherapy

Introduction

The drug therapy of acute myeloid leukemia (AML) and adult acute lymphoblastic leukemia (ALL) is largely based on chemotherapy regimens that have changed little in the past few decades. Patient outcomes for both diseases remain poor, particularly for elderly and high-risk patients. As the limits of cytotoxic chemotherapy are being reached, an unmet need remains for novel, improved therapies.

Scope

*Analysis of the AML and adult ALL market based on a survey of 180 acute leukemia specialists, supported by interviews with key opinion leaders.

*Segmentation of the AML and adult ALL populations by age group and risk group, respectively

*In-depth analysis of treatment patterns, regimens prescribed and treatment outcomes for AML and adult ALL by age group and risk group, respectively

*Discussion of unmet needs and overview of late-stage pipeline drugs and marketed drugs investigated for expansion into the AML and adult ALL settings

Highlights

The only molecular targeted therapy approved for use in AML is Mylotarg (gemtuzumab ozogamicin; Wyeth) but it's use is limited to elderly, relapsed patients who are not candidates for other chemotherapy. A number of molecular targeted therapies are currently in development for AML but are expected to have minimal impact on patient outcomes.

Gleevec (imatinib; Novartis) is the only molecular targeted therapy used extensively in the treatment of adult ALL. To date, the second generation tyrosine kinase inhibitors Sprycel (dasatinib; Bristol-Myers Squibb) and Tasigna (nilotinib; Novartis) have limited use in the treatment of the disease.

Hematopoietic stem cell transplantation (HSCT) has a central role in the management of both AML and adult ALL. However, it remains an underutilized procedure and its use is often delayed beyond its optimal timing. Research efforts are required to optimize the use of this potentially curative approach.

Reasons to Purchase

*Understand prescribing trends in the AML and adult ALL markets

*Examine unmet need within the AML and adult ALL markets and identify opportunities for new product development

*Enhance commercial positioning by increasing understanding of current dynamics within the AML and adult ALL markets

Report Highlights

[Studien Infos ausblenden]

Overview of pipeline drugs for AML and adult ALL 9
CHAPTER 3 AML: COUNTRY TREATMENT TREES 10
Introduction 10
Acute myeloid leukemia (AML) country treatment trees 10
US 12
Japan 16
France 20
Germany 24
Italy 28
Spain 32
UK 36
CHAPTER 4 AML: PATIENT SEGMENTATION AND EPIDEMIOLOGY 40
Key findings 40
Definition of acute myeloid leukemia (AML) 40
AML is a disease of older age 40
Presentation and diagnosis 41
Symptoms can vary for AML patients 41
Segmentation of the acute myeloid leukemia (AML) population 41
Two classification systems are used in AML 41
Cytogenetics is the most important prognostic factor 42
Age is a major determinant of survival 44
Epidemiology of acute myeloid leukemia (AML) 45
AML accounts for about 30-35% of all leukemias in the seven major markets 45
Forecast incidence of AML in the seven major markets, 2009-2019 46
CHAPTER 5 AML: TREATMENT TRENDS 49
Key findings 49
Summary of acute myeloid leukemia (AML) treatment strategies 49
Treatment rates 50
Induction treatment 53
Induction treatment overview 53
Induction treatment trends in patients less than 60 years old 53
Standard-dose cytarabine with idarubicin is the most popular regimen 55
There is a low uptake of the hypomethylating agents Vidaza and Dacogen 56
Induction treatment trends in patients aged 60 or above 57
The treatment of older AML patients deviates from treatment guidelines 59
The uptake of Vidaza and Dacogen is significant in the US 61
Post-induction treatment 63
Post-induction treatment overview 63
Post-induction treatment trends in patients less than 60 years old 63
Post-induction treatment trends in patients aged 60 or above 66
Consolidation treatment 69
Consolidation treatment overview 69
Consolidation treatment trends in patients less than 60 years old 69
Consolidation treatment trends in patients aged 60 or above 72
Relapse treatment 74
Relapse treatment overview 74
Relapse treatment trends in patients less than 60 years old 74
Relapse treatment trends in patients aged 60 or above 78
Mylotarg accounts for about 10% of the market in older, relapsed AML patients 80
Hematopoietic stem cell transplantation in acute myeloid leukemia (AML) 82
CHAPTER 6 AML: IMPROVING TREATMENT OUTCOMES 86
Key findings 86
Treatment outcomes 86
Unmet needs 87
More effective therapies are required for AML 87
HSCT remains an underutilized procedure 87
Molecular markers may help improve risk-adapted therapeutic strategies 88
New product development 88
A number of new approaches are being investigated in AML 88
Novel drugs in Phase III development for AML 89
Onrigin (laromustine; Vion) 91
Zarnestra (tipifarnib; Johnson & Johnson) 92
Amonafide malate (AS1413; Antisoma) 93
Midostaurin (Novartis) 94
PR1 peptide antigen vaccine (The Vaccine Company) 95
Selected marketed drugs investigated in AML 96
Clolar (clofarabine; Genzyme) 97
Dacogen (decitabine; Eisai/Johnson & Johnson) 97
Vidaza (azacitidine; Celgene) 98
Trisenox (arsenic trioxide; Cephalon) 99
CHAPTER 7 ALL: COUNTRY TREATMENT TREES 100
Introduction 100
Acute lymphoblastic leukemia (ALL) country treatment trees 100
US 102
Japan 105
France 107
Germany 109
Italy 111
Spain 113
UK 115
CHAPTER 8 ALL: PATIENT SEGMENTATION AND EPIDEMIOLOGY 117
Definition of acute lymphoblastic leukemia (ALL) 117
ALL represents less than 1% of all adult cancers 117
Genetic alterations provide insight into the pathogenesis of ALL 118
Presentation and diagnosis 119
Non-specific syndromes are common in ALL 119
Segmentation of the ALL population 119
The classification of ALL is still evolving 119
Patients are usually stratified according to risk 120
Age: treatment outcomes decline with increasing patient age 121
Immunophenotype: the outcome of T-lineage ALL is more favorable 122
Cytogenetics and molecular genetics: the Philadelphia chromosome 122
Response to therapy: early response to treatment is a critical prognostic factor 123
Epidemiology of ALL 124
ALL accounts for about 10-15% of all leukemias in the seven major markets 124
Forecast incidence of ALL in the seven major markets, 2009-2019 125
CHAPTER 9 ALL: TREATMENT TRENDS 127
Summary of acute lymphoblastic leukemia (ALL) treatment strategies 127
Treatment rates 128
Induction treatment 130
Induction treatment overview 130
The treatment of Philadelphia chromosome-positive ALL 130
Induction treatment trends 131
A vincristine-corticosteroid combination is the backbone of induction therapy 134
The toxicity of asparaginase compromises its use 135
HyperCVAD is a standard induction therapy in the US 136
Gleevec is the only molecular targeted therapy used extensively in the induction treatment of adult ALL 136
Consolidation treatment 137
Consolidation treatment overview 137
Consolidation treatment trends 138
Consolidation therapy of standard-risk ALL patients is largely based on methotrexate 141
Gleevec is used as a consolidation therapy in Ph+ patients who cannot receive a stem cell transplant 144
Maintenance treatment 145
Maintenance treatment overview 145
Maintenance treatment trends 146
A very small, off-label use of Tasigna is taking place in the maintenance setting 148
Clinical trials in ALL 151
Hematopoietic stem cell transplantation in ALL 154
CHAPTER 10 ALL: IMPROVING TREATMENT OUTCOMES 158
Treatment outcomes 158
Unmet needs 159
More effective therapies are required for adult ALL 159
Research efforts should focus on older ALL patients 159
Prognostic markers are required for risk-adapted therapeutic strategies 160
New product development 160
R&D activity in ALL is limited 160
Novel drugs in late-phase development for adult ALL 163
Marqibo (liposomal vincristine; Hana BioSciences) 163
Selected marketed drugs investigated in adult ALL 165
Arranon (nelarabine; GlaxoSmithKline) 165
Clolar (clofarabine; Genzyme) 165
Rituxan (rituximab; Biogen Idec/Genentech/Roche) 166
BIBLIOGRAPHY 168
Journals 168
Websites 175
Datamonitor reports 177
APPENDIX A 178
List of tables 178
List of figures 178
Physician research methodology 178
Physician sample breakdown 178
US 178
Japan 179
France 179
Germany 180
Italy 180
Spain 181
UK 181
Contributing experts 182
APPENDIX B 183
The survey questionnaire 183
About Datamonitor 196
About Datamonitor Healthcare 196
About the Oncology analysis team 197
Disclaimer 199
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List of Tables
List of Figures
Figure 1: Acute myeloid leukemia (AML) incidence and patient segmentation data in the US for patients less than 60 years old, 2009 12
Figure 2: Acute myeloid leukemia (AML) incidence and patient segmentation data in the US for patients aged 60 or older, 2009 13
Figure 3: Acute myeloid leukemia (AML) treatment data in the US for patients less than 60 years old, 2009 14
Figure 4: Acute myeloid leukemia (AML) treatment data in the US for patients aged 60 or older, 2009 15
Figure 5: Acute myeloid leukemia (AML) incidence and patient segmentation data in Japan for patients less than 60 years old, 2009 16
Figure 6: Acute myeloid leukemia (AML) incidence and patient segmentation data in Japan for patients aged 60 or older, 2009 17
Figure 7: Acute myeloid leukemia (AML) treatment data in Japan for patients less than 60 years old, 2009 18
Figure 8: Acute myeloid leukemia (AML) treatment data in Japan for patients aged 60 or older, 2009 19
Figure 9: Acute myeloid leukemia (AML) incidence and patient segmentation data in France for patients less than 60 years old, 2009 20
Figure 10: Acute myeloid leukemia (AML) incidence and patient segmentation data in France for patients aged 60 or older, 2009 21
Figure 11: Acute myeloid leukemia (AML) treatment data in France for patients less than 60 years old, 2009 22
Figure 12: Acute myeloid leukemia (AML) treatment data in France for patients aged 60 or older, 2009 23
Figure 13: Acute myeloid leukemia (AML) incidence and patient segmentation data in Germany for patients less than 60 years old, 2009 24
Figure 14: Acute myeloid leukemia (AML) incidence and patient segmentation data in Germany for patients aged 60 or older, 2009 25
Figure 15: Acute myeloid leukemia (AML) treatment data in Germany for patients less than 60 years old, 2009 26
Figure 16: Acute myeloid leukemia (AML) treatment data in Germany for patients aged 60 or older, 2009 27
Figure 17: Acute myeloid leukemia (AML) incidence and patient segmentation data in Italy for patients less than 60 years old, 2009 28
Figure 18: Acute myeloid leukemia (AML) incidence and patient segmentation data in Italy for patients aged 60 or older, 2009 29
Figure 19: Acute myeloid leukemia (AML) treatment data in Italy for patients less than 60 years old, 2009 30
Figure 20: Acute myeloid leukemia (AML) treatment data in Italy for patients aged 60 or older, 2009 30
Figure 21: Acute myeloid leukemia (AML) incidence and patient segmentation data in Spain for patients less than 60 years old, 2009 32
Figure 22: Acute myeloid leukemia (AML) incidence and patient segmentation data in Spain for patients aged 60 or older, 2009 33
Figure 23: Acute myeloid leukemia (AML) treatment data in Spain for patients less than 60 years old, 2009 34
Figure 24: Acute myeloid leukemia (AML) treatment data in Spain for patients aged 60 or older, 2009 35
Figure 25: Acute myeloid leukemia (AML) incidence and patient segmentation data in the UK for patients less than 60 years old, 2009 36
Figure 26: Acute myeloid leukemia (AML) incidence and patient segmentation data in the UK for patients aged 60 or older, 2009 37
Figure 27: Acute myeloid leukemia (AML) treatment data in the UK for patients less than 60 years old, 2009 38
Figure 28: Acute myeloid leukemia (AML) treatment data in the UK for patients aged 60 or older, 2009 39
Figure 29: Age distribution of acute myeloid leukemia (AML) patients 45
Figure 30: Percentage distribution of leukemia subtypes in the US, Japan and the five major EU markets, 2009 46
Figure 31: Average treatment rate for acute myeloid leukemia (AML) patients less than 60 years old in the seven major pharmaceutical markets, 2009 51
Figure 32: Average treatment rate for acute myeloid leukemia (AML) patients aged 60 or above in the seven major pharmaceutical markets, 2009 52
Figure 33: Top three chemotherapy regimens used in the induction therapy of acute myeloid leukemia (AML) patients less than 60 years old in the seven major pharmaceutical markets, 2009 55
Figure 34: Top three chemotherapy regimens used in the induction therapy of acute myeloid leukemia (AML) patients aged 60 or above in the seven major pharmaceutical markets, 2009 59
Figure 35: Uptake of Dacogen and Vidaza in the treatment of acute myeloid leukemia (AML) in the US, 2009 61
Figure 36: Top three chemotherapy regimens used in the post-induction therapy of acute myeloid leukemia (AML) patients less than 60 years old in the seven major pharmaceutical markets, 2009 65
Figure 37: Top three chemotherapy regimens used in the post-induction therapy of acute myeloid leukemia (AML) patients aged 60 or above in the seven major pharmaceutical markets, 2009 68
Figure 38: Top three chemotherapy regimens used in the consolidation therapy of acute myeloid leukemia (AML) patients less than 60 years old in the seven major pharmaceutical markets, 2009 71
Figure 39: Top three chemotherapy regimens used in the consolidation therapy of acute myeloid leukemia (AML) patients aged 60 or above in the seven major pharmaceutical markets, 2009 73
Figure 40: Top three chemotherapy regimens used in the relapse therapy of acute myeloid leukemia (AML) patients less than 60 years old in the seven major pharmaceutical markets, 2009 77
Figure 41: Top three chemotherapy regimens used in the relapse therapy of acute myeloid leukemia (AML) patients aged 60 or above in the seven major pharmaceutical markets, 2009 80
Figure 42: Uptake of Mylotarg in the treatment of acute myeloid leukemia (AML) in patients aged under 60 and in patients aged 60 or above, 2009 81
Figure 43: Average use of hematopoietic stem cell transplantation (HSCT) in the induction, post-induction, consolidation, and relapse treatment of AML in the seven major pharmaceutical markets, 2009 83
Figure 44: Adult acute lymphoblastic leukemia (ALL) incidence and patient segmentation data in the US, 2009 102
Figure 45: Adult acute lymphoblastic leukemia (ALL) treatment data in the US, 2009 103
Figure 46: Adult acute lymphoblastic leukemia (ALL) incidence and patient segmentation data in Japan, 2009 105
Figure 47: Adult acute lymphoblastic leukemia (ALL) treatment data in Japan, 2009 106
Figure 48: Adult acute lymphoblastic leukemia (ALL) incidence and patient segmentation data in France, 2009 107
Figure 49: Adult acute lymphoblastic leukemia (ALL) treatment data in France, 2009 108
Figure 50: Adult acute lymphoblastic leukemia (ALL) incidence and patient segmentation data in Germany, 2009 109
Figure 51: Adult acute lymphoblastic leukemia (ALL) treatment data in Germany, 2009 110
Figure 52: Adult acute lymphoblastic leukemia (ALL) incidence and patient segmentation data in Italy, 2009 111
Figure 53: Adult acute lymphoblastic leukemia (ALL) treatment data in Italy, 2009 112
Figure 54: Adult acute lymphoblastic leukemia (ALL) incidence and patient segmentation data in Spain, 2009 113
Figure 55: Adult acute lymphoblastic leukemia (ALL) treatment data in Spain, 2009 114
Figure 56: Adult acute lymphoblastic leukemia (ALL) incidence and patient segmentation data in the UK, 2009 115
Figure 57: Adult acute lymphoblastic leukemia (ALL) treatment data in the UK, 2009 116
Figure 58: Risk stratification of adult acute lymphoblastic leukemia (ALL) patients in the seven major pharmaceutical markets, 2009 121
Figure 59: Philadelphia chromosome status in high-risk adult acute lymphoblastic leukemia (ALL) patients in the seven major pharmaceutical markets, 2009 123
Figure 60: Percentage distribution of leukemia subtypes in the US, Japan and the five major EU markets, 2009 124
Figure 61: Age distribution of childhood and adult acute lymphoblastic leukemia (ALL) in the seven major markets, 2009 126
Figure 62: Average treatment rates for adult acute lymphoblastic leukemia (ALL) patients in the seven major pharmaceutical markets, 2009 129
Figure 63: Top three chemotherapy regimens used in the induction therapy of adult acute lymphoblastic leukemia (ALL) in the seven major pharmaceutical markets, 2009 134
Figure 64: Top three chemotherapy regimens used in the consolidation therapy of standard-risk adult acute lymphoblastic leukemia (ALL) in the seven major pharmaceutical markets, 2009 141
Figure 65: Top three chemotherapy regimens used in the consolidation therapy of high-risk adult acute lymphoblastic leukemia (ALL) in the seven major pharmaceutical markets, 2009 143
Figure 66: Top three chemotherapy regimens used in the maintenance therapy of standard-risk adult acute lymphoblastic leukemia (ALL) in the seven major pharmaceutical markets, 2009 147
Figure 67: Top three chemotherapy regimens used in the maintenance therapy of high-risk adult acute lymphoblastic leukemia (ALL) in the seven major pharmaceutical markets, 2009 150
Figure 68: Average use of clinical trials in the induction, consolidation, and maintenance therapy of adult acute lymphoblastic leukemia (ALL) in the seven major pharmaceutical markets, 2009 151
Figure 69: Average use of hematopoietic stem cell transplantation in the consolidation and maintenance therapy of adult acute lymphoblastic leukemia (ALL) in the seven major pharmaceutical markets, 2009 155
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