Stakeholder Insight: Non-Hodgkin's Lymphomas Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL)

Introduction

The treatment outcomes for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients have improved since the introduction of Rituxan/MabThera (rituximab; Biogen Idec/Genentech/Roche/Chugai/Zenyaku Kogyo). However, an unmet need remains for novel agents with improved efficacy and toxicity profiles, particularly in the treatment of relapsed and refractory patients.

Scope

*Analysis of the DLBCL and FL market based on a survey of 180 non-Hodgkin's lymphomas specialists, supported by interviews with key opinion leaders

*Forecast of the DLBCL and FL patient populations in the seven major pharmaceutical markets

*In-depth analysis of treatment patterns, regimens prescribed and treatment outcomes for DLBCL and FL patients

*Discussion of unmet needs and overview of late-stage pipeline drugs and marketed drugs investigated for expansion into the DLBCL and FL settings

Highlights

Treatment of DLBCL patients with Rituxan has increased cure rates. However, relapsed/refractory patients who are ineligible for stem cell transplant and patients who relapse following transplantation continue to have a poor prognosis. The drugs currently in late Phase development for DLBCL are expected to have minimal impact on patient prognosis.

Current treatment options in advanced FL are rarely curative but Rituxan has been shown to improve prognosis. Patients with advanced disease inevitably relapse and require further treatment. A need remains for novel therapies in the treatment of relapsed/refractory FL to improve survival rates in this hard-to-treat patient population.

The combination of Treanda (bendamustine) with Rituxan has a favorable toxicity profile and has been shown to be effective in the treatment of low-grade NHL. Recent promising clinical trial results suggest that this drug combination has the potential to become a standard of care in the treatment of patients with FL.

Reasons to Purchase

*Understand prescribing trends in the DLBCL and FL markets

*Examine unmet need within the DLBCL and FL markets and identify opportunities for new product development

*Enhance commercial positioning by increasing understanding of current dynamics within the DLBCL and FL markets


Report Highlights

[Studien Infos ausblenden]

TABLE OF CONTENTS
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the NHL market 3
Contributing experts 5
Related reports 6
Upcoming related reports 6
CHAPTER 2 INTRODUCTION AND SCOPE 15
Disease definition and epidemiology 15
Current treatment practice for DLBCL and FL 15
Treatment trends for DLBCL and FL 15
Improving treatment outcomes 15
Assumptions and caveats 16
CHAPTER 3 EPIDEMIOLOGY AND PATIENT SEGMENTATION 17
Introduction 17
Disease classification 18
NHL is classified under the WHO classification system 18
NHL can follow an aggressive or indolent disease course 18
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma 20
Follicular lymphoma (FL) is an indolent lymphoma 20
FL is graded according to the proportion of large cells in the lymphoma 20
Immunophenotype differs between NHL subtypes 21
Diagnosis, staging and prognosis in non-Hodgkin’s lymphomas (NHL) 22
Diagnosis of NHL 22
Ann Arbor staging system 23
The Ann Arbor classification is used for staging NHL but is of limited prognostic use 23
Determining prognosis for NHL 25
International Prognostic Index (IPI) for aggressive NHL 25
International Prognostic Index for FL (FLIPI) 26
Molecular profiling in NHL 28
Etiology 28
Immunodeficiency and immunosuppression as risk factors for non-Hodgkin's lymphomas (NHL) 28
Acquired immunodeficiency syndrome (AIDS) 28
Congenital immunodeficiency 29
Immunosuppressive drugs 29
Autoimmune disorders 29
Infections as risk factors for NHL 29
Human T-cell lymphotrophic virus (HTLV-1) 29
Epstein-Barr virus (EBV) 29
Helicobacter pylori 29
Hepatitis C 30
Occupational, environmental and lifestyle risk factors 30
Pesticides 30
Lifestyle factors 30
Epidemiology 30
NHL cases will total over 125,000 in the seven major markets in 2009 30
Increase in NHL incidence linked to an aging population 32
Forecast incidence of diffuse large B-cell lymphoma (DLBCL) in the seven major markets 34
DLBCL is the most common subtype of NHL 34
Forecast incidence of follicular lymphoma (FL) in the seven major markets. 35
FL is the second most common subtype of NHL 35
CHAPTER 4 TREATMENT TREES: DIFFUSE LARGE B-CELL LYMPHOMA 36
Introduction 36
Diffuse large B-cell lymphoma (DLBCL) treatment trees 36
US 38
Japan 40
France 42
Germany 44
Italy 46
Spain 48
UK 50
CHAPTER 5 TREATMENT TRENDS: DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) 52
Overview 52
Treatment rates 53
Induction therapy 55
R-CHOP is a standard of care for induction therapy in DLBCL 55
Maintenance therapy 59
Second-line therapy 61
Candidates for stem cell transplantation (SCT) 61
Non-candidates for stem cell transplantation (SCT) 65
Stem cell transplantation (SCT) in diffuse large B-cell lymphoma (DLBCL) 68
Third-line therapy 69
Relapse following second-line chemotherapy and stem cell transplantation (SCT) 69
Relapse following second-line chemotherapy alone 72
CHAPTER 6 IMPROVING TREATMENT OUTCOMES: DIFFUSE LARGE B-CELL LYMPHOMA 75
Treatment outcomes 75
Unmet needs 75
Determining the best salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) 75
Inclusion of molecular profiling in current treatment strategies 76
Factors influencing prescribing decision in diffuse large B-cell lymphoma (DLBCL) 77
Efficacy is the most important prescribing influence for DLBCL 77
Incorporation of pipeline drugs into treatment 79
Pixantrone (Cell Therapeutics/Roche) 79
The uptake of pixantrone will depend on its toxicity profile 80
Afinitor (everolimus; Novartis) 81
Afinitor may struggle to secure approval as a maintenance therapy for DLBCL 81
Arzerra (ofatumumab; Genmab/GlaxoSmithKline) 82
Genmab shifts its attention to DLBCL 82
Avastin (bevacizumab; Genentech/Roche/Chugai) 83
Whether the addition of Avastin to R-CHOP improves outcomes in DLBCL is still unclear 84
Revlimid (lenalidomide; Celgene) 85
Revlimid shows good single-agent activity in relapsed/refractory DLBCL patients 85
Enzastaurin (Eli Lilly) 86
Enzastaurin shows marginal single-agent activity in relapsed/refractory DLBCL 87
CHAPTER 7 TREATMENT TREES: FOLLICULAR LYMPHOMA 88
Introduction 88
Follicular lymphoma (FL) treatment trees 88
US 90
Japan 93
France 96
Germany 99
Italy 102
Spain 105
UK 108
CHAPTER 8 TREATMENT TRENDS: FOLLICULAR LYMPHOMA (FL) 111
Overview 111
Treatment rates 112
Induction therapy 114
R-CHOP and R-CVP are the most popular induction regimens 116
The advantage of multiple courses of Rituxan remains unclear 118
Considerable uptake of Rituxan monotherapy in the induction setting 118
Maintenance following induction therapy 119
Rituxan maintenance after first-line and second-line therapy improves PFS and overall survival in FL 119
Second-line therapy 123
Stem cell transplantation (SCT) in follicular lymphoma (FL) 126
The use of reduced-intensity conditioning (RIT) may make allogeneic stem cell transplantation (alloSCT) feasible in more patients 126
Treanda in the treatment of follicular lymphoma 127
Radioimmunotherapies in the treatment of follicular lymphoma 128
Maintenance following second-line therapy 130
Third-line therapy 131
CHAPTER 9 IMPROVING TREATMENT OUTCOMES: FOLLICULAR LYMPHOMA (FL) 134
Treatment outcomes 134
Unmet needs 135
Novel therapies are required to improve treatment outcomes 135
Factors influencing prescribing decisions in follicular lymphoma (FL) 136
Efficacy is the most important prescribing decisions for FL 136
Incorporation of pipeline drugs into treatment 137
Velcade (Millennium/Johnson & Johnson) 138
The combination of Velcade with Rituxan is active in the first-line treatment of indolent non-Hodgkin's lymphomas (NHL) 138
It is unclear how Millennium will position Velcade in the treatment of FL 139
BiovaxID (Biovest/Accentia) 140
Phase III trial data show improvement in PFS, but are not clinically relevant 140
Galiximab (Biogen Idec) 141
Pixantrone (Cell Therapeutics/Roche) 142
Two Phase III trials in indolent non-Hodgkin's lymphomas (NHL) have been closed 142
BIBLIOGRAPHY 144
Journal papers 144
Websites 158
Datamonitor reports 162
APPENDIX A 163
Physician research methodology 163
Physician sample breakdown 163
US 163
Japan 164
France 164
Germany 165
Italy 165
Spain 166
UK 166
Contributing experts 167
APPENDIX B 168
The survey questionnaire 168
Introduction 168
Section 1 – Diffuse large B-cell lymphoma: Patient Segmentation 169
Section 2 – Diffuse large B-cell lymphoma: Treatment 170
Section 3 – Diffuse large B-cell lymphoma: Product Profiles and Pipeline Products 176
Section 4 – Follicular lymphoma: Patient Segmentation 177
Section 5 – Follicular lymphoma: Treatment 178
Section 6 – Follicular lymphoma: Product Profiles and Pipeline Products 183
About Datamonitor 184
About Datamonitor Healthcare 184
About the Oncology analysis team 185
Disclaimer 187



[Inhaltsverzeichnis ausblenden]