ONCAlert | 2017 NANETS Symposium

Redefining Multiple Myeloma Diagnosis and Management

Sikander Ailawadhi, MD
Published Online: Aug 24,2016

Abstract


Our understanding of multiple myeloma including its pathophysiology, clinical behavior, and management, has improved immensely over recent years. This has translated into development of a more diverse portfolio of therapeutic agents and significantly improved patient outcomes, with the survival among standard-risk patients being in the vicinity of 10 years or more. This also has led to redefining some of the basic concepts surrounding this diagnosis, including the very definition of multiple myeloma, response criteria, risk stratification, and goals of treatment. This article reviews some of these concepts that are still evolving, and are thus shaping how we see and manage multiple myeloma - hopefully moving slowly but surely toward its elusive cure.


It is frequently mentioned that the outcomes of patients with multiple myeloma are ever improving, mostly due to the advent of "novel therapeutic agents." It is notable that less than 15 years ago, the diagnosis of multiple myeloma carried a dismal prognosis with no drugs specifically approved by the US Food and Drug Administration (FDA) for its treatment. Since then, not just the therapeutic agents, many of which don't seem "novel" anymore, but our understanding of various other aspects of this disease including its pathophysiology and diagnostic and prognostic techniques have evolved immensely. The goal of this review is to highlight some of these landmark changes that have modified the way we see multiple myeloma and discuss others that are still evolving and that will surely impact the future of patients with this disease, which is so far considered incurable by most.
 

Redefining Multiple Myeloma


While, historically, the definition of active multiple myeloma required treatment to be initiated at the first sign of end-organ damage (per the CRAB criteria),1 it meant that the majority of the patients would not receive treatment to prevent this damage from setting in. This may have been acceptable when the therapeutic options were limited and there was no apparent benefit from early intervention, but in an era when 5-year survival from myeloma is quoted at approximately 50%,2 and some patients are living with this disease for 10 years or longer, the need to prevent end-organ damage rather than merely treating it has become imperative in ensuring improved survivorship and better tolerability to subsequent therapies (TABLE 1).

Considering this, the International Myeloma Working Group (IMWG) has recently updated its definition of active multiple myeloma by adding cases that do not meet the classic CRAB criteria, but that have clonal bone marrow plasma cell percentage ≥60%, involved:uninvolved serum free light-chain ratio ≥100 with the involved serum free light-chain ≥10 mg/dL, or more than 1 focal lesion on magnetic resonance imaging (MRI) studies.3 Furthermore, the widespread utilization and availability of serum and urine free light-chain analyses has decreased the number of truly nonsecretory cases of multiple myeloma, providing measurable markers of disease assessment and response in a larger number of patients. It is also accepted that patients with a biopsy- proven bony or extramedullary plasmacytoma and meeting any of the CRAB criteria even without ≥10% clonal bone marrow plasma cells are treated as active myeloma.3 While all of this certainly will increase the prevalence of active multiple myeloma, it also will affect clinical trial eligibility and outcomes by introducing a subgroup of patients to treatment before the morbidity from the diagnosis affects them.


 



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Redefining Multiple Myeloma Diagnosis and Management
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