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CME / ABIM MOC

IgM-MM Is Predominantly a Pre-Germinal Center Disorder and Has a Distinct Genomic and Transcriptomic Signature From WM

Authors: Abdul Hamid Bazarbachi, MD; Hervé Avet-Loiseau, MD, PhD; Raphael Szalat, MD; Anil Aktas Samur, PhD; Zachary R. Hunter, PhD; Masood A. Shammas, PhD; Jill Corre, PhD; Mariateresa Fulciniti, PhD; Kenneth Carl Anderson, MD; Giovanni Parmigiani, PhD; Steven P. Treon, MD, PhD; Mohamad Mohty, MD, PhD; Nikhil C. Munshi, MD; Mehmet Kemal Samur, PhD
CME / ABIM MOC Released: 11/18/2021
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 11/18/2022

Target Audience and Goal Statement

This activity is intended for hematologists, oncologists, internists, and other clinicians caring for patients with immunoglobulin (Ig)M multiple myeloma (MM).

The goal of this activity is to describe genomic and transcriptomic characteristics of IgM-MM through whole-genome sequencing (WGS) on cluster of differentiation (CD)138-sorted myeloma cells from 15 IgM-MM, 211 non-IgM-MM and 55 Waldenström macroglobulinemia (WM) patient samples, and transcriptome sequencing of 15 IgM-MM cases compared with 30 non-IgM MM, 35 WM, and 3 healthy donor plasma cells (PCs).

Upon completion of this activity, participants will:

Describe genomic and transcriptomic characteristics of immunoglobulin M (IgM)–multiple myeloma (MM) through whole-genome sequencing and transcriptome sequencing of IgM-MM cases compared with non-IgM-MM, Waldenström macroglobulinemia (WM), and healthy donor PCs
Determine driver mutations in IgM-MM compared with non-IgM-MM, WM, and healthy donor plasma cells
Identify which IgM monoclonal gammopathy of undetermined significance has the potential to progress to IgM MM or WM
Identify therapeutic targets in IgM-MM, according to this genomic and transcriptomic study

Disclosures

As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

Faculty

Abdul Hamid Bazarbachi, MD

Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston, Massachusetts
Department of Internal Medicine
Jacobi Medical Center
Albert Einstein College of Medicine
New York, New York

Disclosures

Disclosure: Abdul Hamid Bazarbachi, MD, has disclosed no relevant financial relationships.

Hervé Avet-Loiseau, MD, PhD

University Cancer Center of Toulouse Institut National de la Santé
Toulouse, France

Disclosures

Disclosure: Hervé Avet-Loiseau, MD, PhD, has disclosed no relevant financial relationships.

Raphael Szalat, MD

Department of Hematology and Medical Oncology
Boston University Medical Center
Boston, Massachusetts

Disclosures

Disclosure: Raphael Szalat, MD, has disclosed no relevant financial relationships.

Anil Aktas Samur, PhD

Department of Data Science
Dana-Farber Cancer Institute
Department of Biostatistics
Harvard T.H. Chan School of Public Health
Boston, Massachusetts

Disclosures

Disclosure: Anil Aktas Samur, PhD, has disclosed no relevant financial relationships.

Zachary R. Hunter, PhD

Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston, Massachusetts

Disclosures

Disclosure: Zachary R. Hunter, PhD, has disclosed no relevant financial relationships.

Masood A. Shammas, PhD

Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston, Massachusetts

Disclosures

Disclosure: Masood A. Shammas, PhD, has disclosed no relevant financial relationships.

Jill Corre, PhD

University Cancer Center of Toulouse Institut National de la Santé
Toulouse, France

Disclosures

Disclosure: Jill Corre, PhD, has disclosed no relevant financial relationships.

Mariateresa Fulciniti, PhD

Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston, Massachusetts

Disclosures

Disclosure: Mariateresa Fulciniti, PhD, has disclosed no relevant financial relationships.

Kenneth Carl Anderson, MD

Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston, Massachusetts

Disclosures

Disclosure: Kenneth Carl Anderson, MD, has disclosed the following relevant financial relationships:
Serve(d) as advisor or consultant for: Bristol-Myers Squibb Company; Celgene Corporation; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Precision BioSciences; Sanofi; Takeda Pharmaceuticals North America, Inc.; Tolero Pharmaceuticals
Other (Board of Directors and stock options): OncoPep

Giovanni Parmigiani, PhD

Department of Data Science
Dana-Farber Cancer Institute
Department of Biostatistics
Harvard T.H. Chan School of Public Health
Boston, Massachusetts

Disclosures

Disclosure: Giovanni Parmigiani, PhD, has disclosed no relevant financial relationships.

Steven P. Treon, MD, PhD

Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston, Massachusetts

Disclosures

Disclosure: Steven P. Treon, MD, PhD, has disclosed no relevant financial relationships.

Mohamad Mohty, MD, PhD

Service d’hématologie clinique et thérapie cellulaire
Hôpital Saint-Antoine
INSERM UMRs 938 and université Sorbonne
Paris, France

Disclosures

Disclosure: Mohamad Mohty, MD, PhD, has disclosed no relevant financial relationships.

Nikhil C. Munshi, MD

Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
VA Boston Healthcare System
Boston, Massachusetts

Disclosures

Disclosure: Nikhil C. Munshi, MD, has disclosed the following relevant financial relationships:
Serve(d) as advisor or consultant for: AbbVie, Inc.; Amgen Inc.; Bristol-Myers Squibb Company; GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Karyopharm Therapeutics Inc.; Legend Biotech; OncoPep; Takeda Pharmaceuticals North America, Inc.
Other (Board of Directors and stock options): Oncopep

Mehmet Kemal Samur, PhD

Department of Data Science
Dana-Farber Cancer Institute
Department of Biostatistics
Harvard T.H. Chan School of Public Health
Boston, Massachusetts

Disclosures

Disclosure: Mehmet Kemal Samur, PhD, has disclosed no relevant financial relationships.

CME Author

Laurie Barclay, MD

Freelance writer and reviewer
Medscape, LLC

Disclosures

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor

Andrew Roberts, MBBS, PhD

Deputy Editor, Blood

Disclosures

Disclosure: Andrew Roberts, MBBS, PhD, has disclosed the following relevant financial relationships:
Received grants for clinical research from: His organization, The Walter and Eliza Hall Institute, received grants for clinical research from AbbVie Inc.; Janssen Pharmaceuticals, Inc.
Other: His organization, The Walter and Eliza Hall Institute, received royalties related to venetoclax and will control any distribution based on their institutional policies about scientific contribution to commercial income.

CME Reviewer

Amanda Jett, PharmD, BCACP

Associate Director, Accreditation and Compliance
Medscape, LLC

Disclosures

Disclosure: Amanda Jett, PharmD, BCACP, has disclosed no relevant financial relationships.

None of the nonfaculty planners for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

Accreditation Statements

In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and the American Society of Hematology. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

For Physicians

Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 70% on the post-test.

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*The credit that you receive is based on your user profile.

From Blood

CME / ABIM MOC

IgM-MM Is Predominantly a Pre-Germinal Center Disorder and Has a Distinct Genomic and Transcriptomic Signature From WM

Authors: Abdul Hamid Bazarbachi, MD; Hervé Avet-Loiseau, MD, PhD; Raphael Szalat, MD; Anil Aktas Samur, PhD; Zachary R. Hunter, PhD; Masood A. Shammas, PhD; Jill Corre, PhD; Mariateresa Fulciniti, PhD; Kenneth Carl Anderson, MD; Giovanni Parmigiani, PhD; Steven P. Treon, MD, PhD; Mohamad Mohty, MD, PhD; Nikhil C. Munshi, MD; Mehmet Kemal Samur, PhDFaculty and Disclosures

THIS ACTIVITY HAS EXPIRED FOR CREDIT

CME / ABIM MOC Released: 11/18/2021

Valid for credit through: 11/18/2022

processing....

Abstract and Introduction

Abstract

Immunoglobulin M (IgM) multiple myeloma (MM) is a rare disease subgroup. Its differentiation from other IgM-producing gammopathies such as Waldenström macroglobulinemia (WM) has not been well characterized but is essential for proper risk assessment and treatment. In this study, we investigated genomic and transcriptomic characteristics of IgMMM samples using whole-genome and transcriptome sequencing to identify differentiating characteristics from non–IgM-MM and WM. Our results suggest that IgM-MM shares most of its defining structural variants and gene-expression profiling with MM, but has some key characteristics, including t(11;14) translocation, chromosome 6 and 13 deletion as well as distinct molecular and transcription-factor signatures. Furthermore, IgM-MM translocations were predominantly characterized by V_HD_HJ_H recombination-induced breakpoints, as opposed to the usual class-switching region breakpoints; coupled with its lack of class switching, these data favor a pre–germinal center origin. Finally, we found elevated expression of clinically relevant targets, including CD20 and Bruton tyrosine kinase, as well as high BCL2/BCL2L1 ratio in IgM-MM, providing potential for targeted therapeutics.

Introduction

Immunoglobulin M (IgM) multiple myeloma (MM) is a rare condition with an estimated incidence of <0.5%.^[1] Its differentiation from more common IgM-producing plasma cell (PC) disorders, chiefly Waldenström macroglobulinemia (WM), is challenging but essential because of distinct treatment modalities and prognoses.^[2] Recent advancements in molecular techniques have shed light on the genomic characteristics and unique genetic alterations of MM and WM;^[3,4] however, comprehensive profiling has not yet been performed for IgM-MM. This study investigates genomic and transcriptomic characteristics of IgM-MM through whole-genome (WGS) and transcriptome sequencing of IgM-MM cases, comparing them to non–IgM-MM, WM, and healthy donor PC.

Page 1 of 3

Study Design

CME / ABIM MOC Information

Abstract and Introduction
Study Design
Results and Discussion

Disclaimer

The educational activity presented above may involve simulated, case-based scenarios. The patients depicted in these scenarios are fictitious and no association with any actual patient, whether living or deceased, is intended or should be inferred. The material presented here does not necessarily reflect the views of Medscape, LLC, or any individuals or commercial entities that support companies that support educational programming on medscape.org. These materials may include discussion of therapeutic products that have not been approved by the US Food and Drug Administration, off-label uses of approved products, or data that were presented in abstract form. These data should be considered preliminary until published in a peer-reviewed journal. Readers should verify all information and data before treating patients or employing any therapies described in this or any educational activity. A qualified healthcare professional should be consulted before using any therapeutic product discussed herein.

References

Faculty and Disclosures

Faculty

Abdul Hamid Bazarbachi, MD

Hervé Avet-Loiseau, MD, PhD

Raphael Szalat, MD

Anil Aktas Samur, PhD

Zachary R. Hunter, PhD

Masood A. Shammas, PhD

Jill Corre, PhD

Mariateresa Fulciniti, PhD

Kenneth Carl Anderson, MD

Giovanni Parmigiani, PhD

Steven P. Treon, MD, PhD

Mohamad Mohty, MD, PhD

Nikhil C. Munshi, MD

Mehmet Kemal Samur, PhD

CME Author

Laurie Barclay, MD

Editor

Andrew Roberts, MBBS, PhD

CME Reviewer

Amanda Jett, PharmD, BCACP

CME / ABIM MOC

IgM-MM Is Predominantly a Pre-Germinal Center Disorder and Has a Distinct Genomic and Transcriptomic Signature From WM

Target Audience and Goal Statement

Disclosures

Faculty

Abdul Hamid Bazarbachi, MD

Hervé Avet-Loiseau, MD, PhD

Raphael Szalat, MD

Anil Aktas Samur, PhD

Zachary R. Hunter, PhD

Masood A. Shammas, PhD

Jill Corre, PhD

Mariateresa Fulciniti, PhD

Kenneth Carl Anderson, MD

Giovanni Parmigiani, PhD

Steven P. Treon, MD, PhD

Mohamad Mohty, MD, PhD

Nikhil C. Munshi, MD

Mehmet Kemal Samur, PhD

CME Author

Laurie Barclay, MD

Editor

Andrew Roberts, MBBS, PhD

CME Reviewer

Amanda Jett, PharmD, BCACP

Accreditation Statements

For Physicians

Instructions for Participation and Credit

IgM-MM Is Predominantly a Pre-Germinal Center Disorder and Has a Distinct Genomic and Transcriptomic Signature From WM

Abstract and Introduction

Abstract

Introduction

Table of Contents