New Developments in Myeloma, An Issue of Hematology/Oncology Clinics of North America

1st Edition, Volume 38-2 - March 1, 2024
Editor: Peter Leif Bergsagel
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 0 7 7 - 9
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 0 7 8 - 6

In this issue of Hematology/Oncology Clinics, guest editor Dr. P. Leif Bergsagel brings his considerable expertise to the topic of New Developments in Myeloma. With the advent of… Read more

New Developments in Myeloma, An Issue of Hematology/Oncology Clinics of North America

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In this issue of Hematology/Oncology Clinics, guest editor Dr. P. Leif Bergsagel brings his considerable expertise to the topic of New Developments in Myeloma. With the advent of next generation sequencing and immune profiling technologies, marked advances have been made recently in the understanding of the molecular and immune pathogenesis of multiple myeloma. Yet even with these advances, there is a continual search for new therapeutic approaches. In this issue, top experts discuss a full range of clinically relevant topics in this complex and fast-changing field.

Cover image
Title page
Table of Contents
Copyright
Contributors
Forthcoming Issues
Preface
Dedication
Molecular Pathogenesis of Multiple Myeloma: Clinical Implications
Key points
Introduction
Multiple myeloma is preceded by an asymptomatic monoclonal gammopathy
Immunoglobulin heavy chain gene translocations and hyperdiploidy are primary genetic events
Secondary genetic events cause the progression to symptomatic multiple myeloma
Impact of intratumor subclonal heterogeneity on disease progression and drug resistance
Summary
Clinics care points
Immune-Pathogenesis of Myeloma
Key points
Introduction
Immune recognition of premalignancy
Role of spatial architecture in multiple myeloma immunopathogenesis
Role of chronic B cell activation
Understanding premonoclonal gammopathy of undetermined significance
Diverse mechanisms underlie immune paresis in multiple myeloma
Nonimmunologic contributions of immune cells in multiple myeloma
Summary and future directions
Clinics care points
Smoldering Multiple Myeloma: Observation Versus Control Versus Cure
Key points
Introduction
Diagnostic criteria and clinical features
Risk stratification
Approach to treatment
Future directions
Clinics care points
Cereblon-Targeting Ligase Degraders in Myeloma: Mechanisms of Action and Resistance
Key points
Introduction
Mechanisms of action
Mechanisms of resistance to immunomodulatory imide drugs and cereblon E3 ligase modulators
CRBN-independent resistance mechanisms
Summary
Clinics care points
Proteasome Inhibitors in Multiple Myeloma: Biological Insights on Mechanisms of Action or Resistance Informed by Functional Genomics
Key points
Introduction
The proteasome complex and its inhibitors
The evolving conceptual framework on molecular mechanisms mediating anti-multiple myeloma effects of proteasome inhibition
Insights from functional genomics of multiple myeloma on the mediators of proteasome inhibitor activity
Current state and future perspectives on mechanisms of resistance to proteasome inhibitors
Future perspectives on the basic and translational studies of proteasome inhibition
Monoclonal Antibodies in the Treatment of Multiple Myeloma
Key points
Introduction
CD38-targeting antibodies
Summary
Clinics care points
Bispecific Antibodies in the Treatment of Multiple Myeloma
Key points
Introduction
Potential bispecific antibody targets and mechanisms of action
Selected clinical data of bispecific antibodies in relapsed/refractory multiple myeloma
Potential resistance mechanisms
Summary and outlook
Clinics care points
Chimeric Antigen Receptor T Cells in the Treatment of Multiple Myeloma
Key points
Introduction
History of chimeric antigen receptor T cell therapy in myeloma
Idecabtagene vicleucel: KarMMa trial and other data in late line multiple myeloma
Ciltacabtagene autoleucel: CARTITUDE-1 and other data in late line multiple myeloma
Chimeric antigen receptor T cells in earlier lines and role of maintenance
Other B cell maturation antigen-directed chimeric antigen receptor T cells in clinical development
Toxicities of chimeric antigen receptor T cell therapies
Non-B cell maturation antigen-directed chimeric antigen receptor T cells for myeloma
Ongoing challenges and potential solutions
Summary
Clinics care points
Is There Still a Role for Stem Cell Transplantation in Multiple Myeloma?
Key points
Introduction
Summary
Clinics care points
Role of Consolidation and Maintenance
Key points
Introduction
Discussion
Summary
Summary and future directions
Clinics care points
Management of Newly Diagnosed Multiple Myeloma Today, and in the Future
Key points
Introduction
Transplant-eligible patients
Transplant-ineligible patients
Future directions
Summary
Clinics care points
Impact of Clonal Heterogeneity in Multiple Myeloma
Key points
Introduction
Initiating and progression events and their impact on outcome
Spatial clonal heterogeneity
Clonal heterogeneity and the bone marrow microenvironment
Clonal heterogeneity and treatment resistance
Overcoming clonal heterogeneity
Summary
Clinics care points
Measurable Residual Disease and Decision-Making in Multiple Myeloma
Key points
Introduction
A primer on measurable residual disease in myeloma
Measurable residual disease as a prognostic tool
Measurable residual disease result interpretation
Measurable residual disease as a surrogate endpoint
Measurable residual disease to guide decision-making
“Hot takes” and burning questions
Clinics care points
Approach to High-Risk Multiple Myeloma
Key points
Introduction
The clinical problem associated with high-risk myeloma
Conceptually what is high-risk myeloma, and how should it be addressed therapeutically?
Cytogenetic markers of high-risk disease
Prognostic scoring systems
Biologic, genetic, and epigenetic features of high risk
The high-risk microenvironment
Therapeutic considerations
Mechanisms of relapse
Consensus definitions
Summary
Clinics care points
New Therapies on the Horizon for Relapsed Refractory Multiple Myeloma
Key points
Introduction
Discussion
Summary
Clinics care points
Immunocompetent Mouse Models of Multiple Myeloma: Therapeutic Implications
Key points
Introduction
Discussion
Summary
Clinics care points

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New Developments in Myeloma, An Issue of Hematology/Oncology Clinics of North America

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Peter Leif Bergsagel