Perspective
Perspectives in the Rapidly Evolving Treatment Landscape of Multiple Myeloma: Expert Review of New Data Presentations from ASH 2019

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Abstract

The number and type of therapeutic options available to treat patients with multiple myeloma has risen dramatically over recent years, offering exciting opportunities to significantly improve the future management of this currently incurable disease. Some of the latest advances in the settings of newly diagnosed and relapsed/refractory multiple myeloma were presented at the 61st Annual Meeting of the American Society of Hematology (Orlando, Florida, December 7 to 10, 2019) and are reviewed in this article with accompanying expert commentary. Presentations covered the use of registry-generated real-world data to define the characteristics of ‘functional’ high-risk patients in order to enable early therapeutic intervention for this poor-prognosis subset; studies that reported impressive new and updated data with novel combinations of targeted agents across different settings, including biomarker-specific subgroups; and promising early-phase data with novel immunotherapeutic approaches, such as bispecific antibodies and chimeric antigen receptor T-cell B-cell maturation antigen-directed therapies. This review offers insights into how these latest developments may fit within the rapidly evolving treatment landscape. The adoption and optimal use of novel therapies may be impacted by logistical challenges such as limited funding and access to necessary infrastructure to provide these treatments. In this manuscript, we focus particularly on Asia-Pacific regions and identify areas for development, such as establishment of robust national registries, promotion of investigator-initiated trials, compassionate-use treatment programs, and collaboration between jurisdictions with similar patterns of care. The hope is that such efforts will augment research outputs and ultimately translate into improved patient outcomes in the real world.

Introduction

Multiple myeloma is one of the most common, yet incurable, hematologic malignancies1; accounting for approximately 10% of all hematologic cancers, it affects mainly elderly individuals, with a median age at diagnosis of 72 years.2

Recent years have seen a dramatic increase in the number and type of therapeutic options available to treat patients with multiple myeloma, resulting in improved patient outcomes.1 These include immunomodulatory agents, such as thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors, such as bortezomib; second-generation proteasome inhibitors, such as carfilzomib and ixazomib; first-in-class small-molecule inhibitors venetoclax (a B-cell lymphoma 2 [BCL-2] inhibitor) and selinexor (a chromosomal region maintenance protein 1 [CRM1] inhibitor); bendamustine, an alkylating agent; panobinostat, a histone deacetylase inhibitor; and monoclonal antibodies, such as elotuzumab and daratumumab.

However, although these therapies offer exciting opportunities to significantly improve patient outcomes, physicians are faced with several challenges, such as keeping abreast of the latest developments, and determining which agents and which combinations/sequences of agents (of those that are locally available/reimbursed) to use across different settings. Furthermore, the adoption and optimal use of these novel therapies may be compromised, not only by limited funding, but also by the absence of necessary infrastructure, such as molecular testing facilities and national registries to provide real-world evidence.

This article reviews some of the most compelling new clinical data presented on multiple myeloma at the 61st Annual Meeting of the American Society of Hematology (ASH) held in Orlando, Florida (December 7-10, 2019), and offers perspectives and insights into how these latest developments may fit within the rapidly evolving treatment landscape, based on expert discussions at a Scientific Debrief meeting held at ASH. Gaps in treatment practice relating to the optimal use of approved and investigational agents across Asia-Pacific regions relevant to the ASH 2019 data are identified, and practicalities and challenges in patient management among Asian and Western countries are discussed. The often limited applicability of clinical trial data to the real-world setting, and the considerable value of information collected through registries and investigator-initiated trials, are also considered.

As mentioned above, the data reviewed in this article were reported in congress abstracts/presentations rather than in the peer-reviewed literature. The abstracts selected for review are those that the authors consider will most likely be impactful across the multiple myeloma treatment landscape in the foreseeable future, especially within Asia-Pacific regions, and are grouped into 3 main sections: newly diagnosed multiple myeloma (NDMM), relapsed/refractory multiple myeloma (RRMM), and novel therapies. The aim is to provide insights and perspectives with a regional context, which are based on expert opinion, rather than treatment recommendations based on unpublished data.

Section snippets

Defining Functional High-risk Patients to Inform Response-adaptive Strategies

In the management of NDMM, it is necessary to identify functional high-risk patients (median survival < 24 months from diagnosis) at an early stage of treatment – a group with ongoing unmet therapeutic needs. The Revised International Staging System3 is the most commonly used risk-stratification model in multiple myeloma, but this does not capture all functional high-risk disease, and there are barriers to risk stratification in some jurisdictions (owing to limited access to cytogenetic or

Discussion

It is important to note that the data reviewed in this article are based on congress abstracts/presentations rather than peer-reviewed publications. However, they reflect the rapidly evolving treatment landscape for multiple myeloma, with impressive new data for targeted therapy combinations, including proteasome inhibitors, and immunomodulatory and antibody-based approaches, together with early yet promising data on investigational BCMA-directed immunotherapies such as bispecific antibodies

Summary

In summary, the heterogeneity of multiple myeloma requires an individualized approach to treatment, requiring consideration of many factors. As highlighted in the data presented at ASH, patient risk stratification, identification and effective use of predictive biomarkers of response, and elucidation of optimal combinations and sequences of novel targeted therapies will all contribute to improved long-term patient outcomes while ensuring an appropriate balance between response and toxicity.

Disclosures

This work was supported by Amgen Asia Holding Ltd. Chng Wee Joo has received grants from Amgen, Janssen, Celgene, and AbbVie, and honoraria from Amgen, Janssen, Celgene, AbbVie, and Takeda. Hang Quach has received research grants from Amgen, Celgene, Karyopharm, and GlaxoSmithKline; research drug supplies from Sanofi; and is an advisory board member for Amgen, Celgene, Karyopharm, GlaxoSmithKline, Janssen Cilag, and Specialized Therapeutics. Noopur Raje has received research funding from

Acknowledgments

The authors would like to thank the following additional contributors who attended the Scientific Debrief meeting at ASH 2019 and contributed to the discussions: Kihyun Kim (Korea), Amit Khot (Australia), Junya Kuroda (Japan), Lugui Qiu (China), Tran-Der Tan (Taiwan), and Sung-Soo Yoon (Korea). Medical writing assistance was provided by Rachel Mason of Lighthouse Medical Communications US, a Lucid Group company, and was funded by Amgen.

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