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About This Activity

Activity Description and Learning Objectives

In this activity, Prof. Graham Jackson discusses the future of precision medicine with emerging biomarkers and novel therapies in the management of relapsed/refractory multiple myeloma.

This activity has been jointly provided by Oakstone and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians.

After watching this activity, participants should be better able to:

Target Audience

This activity is designed to meet the educational needs of haematologists and oncologists globally.

Faculty Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Prof. Graham Jackson disclosures

Speaker for: Amgen, Celgene, Chugai, Janssen Pharmaceuticals, Takeda

Advisory board participation: Amgen, Celgene, Chugai, GlaxoSmithKline, Oncopeptides, Takeda

Research funding from: Amgen, Celgene, Janssen Pharmaceuticals

Content Reviewer

Walter Murray Yarbrough, MD has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Kathy Day has no financial interests/relationships or affiliations in relation to this activity.

Requirement for Successful Completion

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Oakstone Publishing and touchIME.  Oakstone Publishing is accredited by the ACCME to provide continuing medical education for physicians.

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. A score of 70% or higher is needed to obtain CME credit. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Date of original release: June 8, 2020. Date credits expire: June 8, 2021.

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Q1. Which of the following characteristics may be used to identify patients with multiple myeloma at high risk of unmet needs?

  1. A. Younger age (<40 years)
  2. B. Cytogenetic abnormalities (e.g. t(4;14), del17p))
  3. C. Absence of toxicity of organ dysfunction
  4. D. Minimal residual disease (MRD)-negative status

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Identification of high-risk cytogenetic abnormalities such as t(4;14), t(14;16) and del(17p)1 has opened up the possibility of using a biomarker approach to assess patients for high-risk disease whose treatment needs remain an unmet clinical need.1 High-risk patients for relapsed/refractory multiple myeloma also include elderly or frail patients and those with toxicity-related complications and comorbidities.2,3 The presence of myeloma cells in the bone marrow after a clinical response (minimal residual disease) is clinically relevant and may lead to disease progression.3

References

  1. Giao N, et al. Mol Omics. 2019;15:7–20
  2. Minnema M and Gavriaatop M. Eur Oncol Haematol. 2018;14(2):96–104.
  3. Nijhof IS, et al. Drugs. 2018;78(1):19-37.

Q2. Which of the following remains the main challenge in using a risk-driven personalized approach for patients with relapsed/refractory multiple myeloma?

  1. A. Few prognostic genetic biomarkers are available in multiple myeloma
  2. B. There is a lack of sensitivity in biomarker-testing technologies
  3. C. There is a lack of standardization in risk-profiling systems using genetic and molecular biomarkers
  4. D. Absence of predictive biomarkers and druggable targets

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Knowledge of molecular features or biomarker information is useful to improve risk stratification of patients with multiple myeloma to define a high-risk subset.1  However, lack of standardization in risk-profiling systems using genetic and molecular biomarkers remains a challenge, with no uniform definition of high risk agreed.2 For example, t(4;14) is considered intermediate risk by the mSMART profiling systems and high risk by the R-ISS. Biomarkers developed in the context of clinical trials may help to identify patients who would benefit from specific targeted therapies. 1

Abbreviations

mSMART; Mayo Stratification of Myeloma and Risk-Adaptive Therapy; R-ISS, Revised International Staging System.

References

  1. Pawlyn C, Davies F. Blood. 2019;133:660–675.
  2. Giao N, et al. Mol Omics. 2019;15:7–20.

Q3. Which of the following statements best describes the potential for further treatment optimization in patients with relapse/refractory multiple myeloma?

  1. A. Biomarker assessment at diagnosis will inform treatment strategies following relapse
  2. B. Clinical features associated with high-risk patients have been uniformly defined
  3. C. All high-risk patients will benefit from novel targeted approaches
  4. D. Tailored clinical trials that risk-stratify patients will aim to inform a personalized approach

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At diagnosis, identification of high- and low-risk groups is beneficial in selecting the appropriate treatment regimen to maximize the chance of survival. However, heterogeneity and clonal evolution of the disease can lead to therapeutic ineffectiveness during the treatment course.  Early identification of high-risk patients at diagnosis and during the disease course can help to define an appropriate treatment strategy. Given the huge availability of newer and more effective treatments in the near future, once we have received the results of the ongoing clinical trials, we will be able to better draw a tailored therapeutic approach for the high-risk setting.

Reference

  1. Giao N, et al. Mol Omics. 2019;15:7–20.
  2. Giovanni Solimando A, et al. J Clin Med. 2019;8:997.

Q4. A cytogenetic analysis by fluorescence in situ hybridization (FISH) of a patient with relapsed/refractory multiple myeloma indicates that his cancer harbours the t(11;14) mutation. According to the clinical data, which of the following agents would you consider in the context of a risk-driven clinical trial?

  1. A. Targeted antibodies
  2. B. Immune checkpoint inhibitors
  3. C. BCL2 inhibitors
  4. D. BRAF inhibitors

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Risk-stratifying patients with relapsed/refractory multiple myeloma for tailored clinical trials aims to inform a personalized therapeutic approach and optimize outcomes. New investigational treatments that incorporate genomic-directed stratification hold promise to improve or overcome the adverse prognosis of high-risk multiple myeloma.1 The selective BCL2 inhibitor, venetoclax, has been shown in clinical trials to have single-agent activity in patients with heavily treated relapsed/refractory multiple myeloma, predominantly in patients with a t(11;14) mutation.2

References

  1. Giovanni Solimando A, et al. J Clin Med. 2019; 8:997.
  2. Uckun FM, et al. EBioMedicine 2019;39:612-620.
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touchEXPERT OPINIONS

Biomarkers and novel therapies in relapsed/refractory multiple myeloma: Where are we heading in 2020?

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Introduction

Watch leading expert, Prof. Graham Jackson, discuss the importance of identifying high-risk patients with relapsed/refractory multiple myeloma and the role of biomarkers and novel therapies in optimizing individual patient care.

This activity is intended for haematologists and oncologists.

Learning Objectives

After watching this touchEXPERT OPINIONS, you should be able to:

  • Identify those patients with relapsed/refractory multiple myeloma with the most significant unmet needs
  • Describe existing and novel biomarker testing and the relevance for optimizing the treatment of relapsed/refractory multiple myeloma
  • Discuss the evidence for novel treatments and the potential for further treatment optimization with combination treatments in clinical trials and practice