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Diagnosis and management of multiple myeloma

Introduction

Multiple myeloma (MM), the second most common type of blood cancer, is now recognized as a genetically complex and heterogeneous disease. As well as a variable clinical presentation, response to treatment and survival remains heterogeneous, with some patients with MM living for 1–2 years whilst others are alive and progression-free at 10 years. This variation in outcome is due to patient characteristics as well as biologic features of MM.

As a result of recent advances in diagnosis and therapy, there has been a dramatic improvement in the outcome of MM in the last decade. However, MM remains an incurable disease, with relapses and resistances frequently observed, probably due to the genomic complexity and clonal evolution of MM over the course of treatment. Recognizing the heterogeneity in the biology and clinical presentation of patients with newly diagnosed MM, current clinical investigations are moving away from a ‘one size fits all’ treatment paradigm to both risk- and response-adaptive strategies.

This themed collection features a selection of recent full-text articles and chapters from the Springer Nature portfolio that focus on the biologic features of MM, advances in our understanding of the genomic complexity of MM and its clinical implications, and state-of-art diagnostic and therapeutic approaches. Over time this collection will be enhanced by the addition of specially commissioned articles and resources that provide further guidance to healthcare practitioners, as well as selected full-text articles sourced from other prominent publishers.

Diagnosis, staging and clinical features

Genomic complexity of multiple myeloma and its clinical implications

In this review, Manier et al. describe the 'driver' gene alterations involved in the development and progression of multiple myeloma (MM) and discuss the therapeutic implications of a comprehensive understanding of the genomic complexity of MM.

Summary points
  • Multiple myeloma (MM) is a genetically complex and heterogeneous disease resulting from multiple genomic events that lead to tumor development and progression.
  • One of the unique features of MM is the presence of well-defined pre-malignant states termed monoclonal gammaopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).
  • A combination of primary events, secondary genetic events and marked clonal heterogeneity lead to tumor development and progression from MGUS to late-stage MM.
  • This genomic complexity is a challenge to finding effective therapies for patients with MM.
  • Genome-wide association studies have identified seven loci that contribute to inherited genetic susceptibility to MM, and collectively account for ~13% of the familial risk of MM. The complete functional role of these candidate genes remains to be elucidated.
  • In addition, multiple chromosomal translocations, copy-number variations and single-nucleotide events have been described in MM and may be driver events in oncogenesis or secondary events leading to progression.
  • Most likely, several driver events need to coincide for the development and progression of the disease.
  • The existence of clonal heterogeneity adds a layer of complexity by means of clonal competition during disease progression and represents a challenge to the development of targeted therapies  for MM.

Mainer et al. Nat Rev Clin Oncol 2017; 14: 100–113. doi: 10.1038/nrclinonc.2016.122

Pathology of multiple myeloma

In this chapter, Manier et al. describe the 'driver' gene alterations involved in the development and progression of multiple myeloma (MM) and discuss the therapeutic implications of a comprehensive understanding of the genomic complexity of MM.

Summary points
  • The pathologic diagnosis of multiple myeloma (MM) and other plasma cell proliferative disorders (PCPD) is made on the bone marrow aspirate and biopsy specimen.
  • The goal of the pathologic examination of the bone marrow is to: (a) quantify bone marrow plasma cells (PC); (b) establish PC clonality; (c) distinguish MM from lymphoplasmacytic lymphoma (LPL) and other B-cell lymphomas with plasmacytic differentiation; (d) analyze prognostic factors; (e) detect amyloid deposits; and (f) detect other potential pathologic processes.
  • The standard of care for PC quantification is still morphologic assessment of the bone marrow aspirate and biopsy.
  • Clonality of PCs is inferred by showing of monotypic immunoglobulin light chain expression (kappa or lambda) and/or abnormal patterns of antigen expression.
  • Bone marrow examination helps differentiate LPL from MM. In MM, a monomorphic PC population is usually pure without associated lymphoid component, whereas in LPL small lymphocytes and plasmacytoid lymphocytes typically predominate.
  • The most important laboratory prognostic factors are proliferation rate of neoplastic plasma cells and cytogenetic findings.
  • Amyloid accumulation in extracellular space leads to multiple organ dysfunction; amyloid deposits can be detected in the tissue biopsy using Congo Red stain under polarized light.
  • There is a wide range of pathologic processes that can accompany PCPDs. The most common ones are large granular lymphocyte proliferations and therapy-related myeloid neoplasms.

Jevremovic D & Morice W. In: Multiple Myeloma. Edited by Gertz MA & Rajkumar SV. Springer New York, 2014. doi:10.1007/978-1-4614-8520-9_3

Diagnostic advances in multiple myeloma

This review article summarizes advances in diagnostic testing for multiple myeloma, including detection of monoclonal proteins and imaging techniques to diagnose bone lesions and extramedullary disease.

Summary points
  • There have been several advances in the diagnosis of multiple myeloma (MM) in recent years.
  • Serum free light chains (FLC) have improved the ability to diagnose light chain MM; however, there are still difficulties in the serologic diagnosis of MM in some cases, particularly IgA MM. A novel heavy/light chain nephelometric assay (HevyLite) can identify and quantify the M-protein in some of these cases.
  • New evidence supports the use of FLC in bodily fluids such as ascites, pleural effusions, and spinal fluid to diagnose and quantify extramedullary disease.
  • Major advances in diagnostic imaging have changed the International Myeloma Working Group recommendations for the initial evaluation of MM to include whole body low-dose computed tomography, whole body magnetic resonance imaging, and positron emission tomography/computed tomography.

Barley K & Chari A. Curr Hematol Malig Rep 2016; 11: 111–117. doi:10.1007/s11899-016-0314-5

Risk stratification in multiple myeloma

Focusing on the Revised International Staging System, the authors here review current prognostic variables and their significance in the staging of multiple myeloma.

Summary points
  • Multiple myeloma (MM) remains a highly heterogeneous disease with the overall survival ranging from a few months to decades among different cases.
  • There are many variables that affect risk stratification and prognostic factors in MM can be divided into tumor factors or host factors.
  • Tumor biology factors relate to the MM chromosomal abnormalities, gene expression profile, and tumor burden.
  • Lactate dehydrogenase, plasma cell proliferative rate, extramedullary disease and initial presentation as plasma cell leukemia are additional measures of tumor burden.
  • Host-related factors include age, performance status, and comorbidities.
  • The widely used International Staging System (ISS) does not incorporate genetics, age, and other important variables in its risk stratification.
  • Although it has its own limitations, the recently published Revised International Staging System (R-ISS) that was built upon the framework of ISS, is a more comprehensive and predictive tool for MM patients.

Ooi MGM, de Mel S, & Chng WJ. Curr Hematol Malig Rep 2016; 11: 137–147. doi:10.1007/s11899-016-0307-4

Interpretation of cytogenetic results in multiple myeloma for clinical practice

This article reviews how multiple myeloma is classified into specific subtypes based on primary cytogenetic abnormalities and provides a concise overview of how to interpret cytogenetic abnormalities based on the disease stage.

Summary point
  • Multiple myeloma (MM) is a cytogenetically heterogeneous plasma cell malignancy.
  • Cytogenetic abnormalities in MM affect every aspect of the disease, from evolution of the malignancy to clinical presentation, response to therapy and prognosis.
  • The sheer number and complexity of cytogenetic abnormalities that occur in MM and the multiple ways in which each can affect patient care and counseling make the evaluation and interpretation of cytogenetic abnormalities in MM a daunting task.
  • Primary cytogenetic abnormalities classify premalignant monoclonal gammopathy of undetermined significance (MGUS) and MM into several distinct, mostly non-overlapping subtypes, and are believed to have a role in the initial pathogenesis of MGUS.
  • The two main types of primary cytogenetic abnormalities in MM are trisomies and translocations involving the immunoglobulin heavy chain (IgH) gene.
  • Secondary cytogenetic abnormalities can occur in any of the primary subtypes of MM and influence disease outcome to varying degrees.
  • The detection and interpretation of cytogenetic abnormalities in MM is of critical importance for prognosis and risk stratification of MM. In addition, it can also help in the choice of drugs and in selecting overall therapeutic strategy.
  • The importance of cytogenetic evaluation is indicated by the recent incorporation of high-risk cytogenetic abnormalities into the Revised International Staging System for MM.

Rajan AM & Rajkumar SV. Blood Cancer J 2015; 5: e365. doi:10.1038/bcj.2015.92

Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting

Nuclear imaging is an important tool for diagnosis and response monitoring in patients with multiple myeloma (MM). This article reviews the effectiveness of radiopharmaceuticals that target metabolism, surface receptors and angiogenesis in MM.

Summary points
  • Whole-body X-ray (WBX) has been the method of choice for detecting skeleton abnormalities in multiple myeloma (MM). However, its value in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones.
  • Therefore, alternative techniques are necessary to visualize disease activity. The properties of nuclear imaging enable the identification of disease activity by directly targeting the specific cellular properties of malignant plasma cells, such as metabolism, surface receptors and angiogenesis.
  • Various nuclear imaging techniques and tracers have been used for detecting disease activity and bone lesions in newly diagnosed MM patients.
  • Most studies have been performed with [18 F]-FDG-PET. In newly diagnosed MM, [18 F]-FDG-PET detects more lesions, including extramedullary disease, compared to WBX and provides useful information about treatment response and outcome.
  • However, few nuclear imaging studies have been conducted in relapsed MM patients.
  • Nuclear imaging may be helpful in relapsed MM because it is frequently difficult to detect new disease activity with WBX, magnetic resonance imaging or bone marrow biopsy due to its scattered growth pattern.
  • In the future, nuclear tracers may be used for staging and response monitoring of relapsing MM patients.

de Waal EGM et al. Eur J Nucl Med Mol Imaging 2017; 44: 332–341. doi:10.1007/s00259-016-3576-1

Bone disease in multiple myeloma

In this chapter Eda et al. discuss the pathogenesis of osteolytic bone disease and focus on advances in our understanding of its biology and therapeutic implications.

Summary points
  • Bone involvement represented by osteolytic bone disease (OBD) or osteopenia is one of the pathognomonic and defining characteristic of multiple myeloma (MM).
  • OBD negatively impacts both patients’ quality of life and survival, highlighting the importance of treatment strategies that alleviate OBD in MM.
  • OBD is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling; OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu.
  • Inhibition of osteolysis and stimulation of OB differentiation leads to reduced tumor growth in vivo.
  • Novel agents targeting OBD are promising therapeutic strategies not only for the treatment of MM OBD but also for the treatment of MM.
  • Several novel agents in addition to bisphosphonates are currently under investigation for their positive effect on bone remodeling via OC inhibition or OB stimulation.

Eda H et al. In: Plasma Cell Dyscrasias. Edited by Roccaro AM & Ghobrial IM. Springer International Publishing, 2016. doi:10.1007/978-3-319-40320-5_14

Advances in understanding prognosis in myeloma

This review article summarizes current concepts of prognostic markers in myeloma.

Summary points
  • Response to myeloma treatment and survival remains heterogeneous, with some patients living for 1–2 years whilst others are alive and progression-free at 10 years.
  • This variation in outcome is due to patient characteristics plus features intrinsic to the myeloma tumor.
  • Alongside the introduction of novel therapies there has been a greater understanding of disease biology and mechanisms of resistance. This has led to an increase in the number of prognostic markers that can be used in myeloma.
  • This is important not only for more accurate counselling of patients in terms of disease outcome, but also in paving the way for risk-adapted therapy.
  • Indeed, the prognostic value of certain markers varies according to which therapy the patient receives.
  • These prognostic factors will require constant re-evaluation as agents with new mechanisms of action are added into the myeloma treatment algorithm.

Smith D & Yong K. Br J Haematol 2016; 175: 367–380. doi: 10.1111/bjh.14304

Treatment

Defining and treating high-risk multiple myeloma

This article reviews the available data on best therapeutic approaches for high-risk multiple myeloma.

Summary points
  • Multiple myeloma (MM) is more recently being recognized as a heterogeneous group of disease with variability in outcomes based on specific clinical and biologic predictors.
  • This heterogeneity is related to either host features or specific characteristics of the tumor.
  • MM patients can be broadly categorized into standard, intermediate and high risk for disease relapse, morbidity and mortality.
  • By defining high-risk biologic and clinical variables, a strong case can be made for a more precise counseling of the patients regarding their disease prognosis, and for treating patients with investigational agents within the framework of risk-adapted clinical trials.
  • The high-risk features include patient-specific factors such as old age, poor performance status and comorbidities; clinical features such as primary plasma cell leukemia and extramedullary disease; disease-specific biologic features such as deletion 17p, t(4;14) and high-risk gene expression profiling signatures.
  • All high-risk MM patients should be encouraged to participate in clinical trials exploring novel agents and novel treatment strategies.

Usmani SZ et al. ​​​​​​​Leukemia 2015; 29: 2119–2125. doi: 10.1038/leu.2015.209

The role of maintenance therapy in multiple myeloma

​​​​​​​Based on a comprehensive literature search, Lipe et al. analyze the most current literature and to provide recommendations for maintenance therapy in multiple myeloma.

Summary points
  • Multiple myeloma (MM) is the second most common type of blood cancer and remains incurable despite advances in therapy.
  • Therapy for MM is typically administered in a phased approach, which often consists of initial induction therapy, consolidation, and maintenance therapy.
  • There is strong evidence to suggest that maintenance therapy with bortezomib and lenalidomide improves progression-free survival. Data regarding overall survival (OS) is more variable, but at least three trials suggest improved OS with maintenance therapy.
  • As a result of the data, the authors recommend continuous maintenance therapy with lenalidomide/dexamethasone or bortezomib for the transplant-ineligible population (GRADE 2A); the choice of maintenance therapy should be matched to the induction regimen.
  • For patients receiving both lenalidomide and bortezomib during induction, maintenance therapy should be guided by patient preference, toxicity profile, and risk-stratification of disease.
  • For transplant-eligible patients, stratified maintenance therapy should be based on risk features and depth of response. For standard risk patients who have achieved a sustained complete response (CR), lenalidomide maintenance for 2 years (GRADE 2B) is recommended.
  • For patients with less than a CR, indefinite maintenance therapy with lenalidomide (GRADE 2B) is advised. If patients are intolerant or resistant to lenalidomide, bortezomib maintenance should be used (GRADE 2B). A combined bortezomib–lenalidomide or bortezomib-based maintenance strategy for high-risk patients (GRADE 2C) is also recommended.

Lipe et al.​​​​​​​ Blood Cancer J 2016; 6: e485. doi: 10.1038/bcj.2016.89

Novel induction regimens in multiple myeloma

The focus of this review is a critical analysis of combinations of novel agents in the treatment of newly diagnosed multiple myeloma in both transplant eligible and ineligible patients.

Summary points
  • Multiple myeloma (MM) is the second most common hematologic malignancy, accounting for 1% of neoplastic diseases and 13% of hematologic cancers, and predominantly affects the elderly.
  • The introduction of novel therapies such as thalidomide, lenalidomide, and bortezomib for the treatment of MM in the last 15 years has drastically improved progression-free survival (PFS), overall survival (OS), and quality of life for patients with MM.
  • In transplant-eligible patients, the three-drug regimens CyBorD, RVD, and BiRD appear to be the most effective with tolerable adverse effect profile and PFS benefit.
  • Carfilzomib in combination with lenalidomide and dexamethasone has been shown to induce deep responses to the point of negative minimal residual disease state on flow cytometry.
  • In transplant-ineligible patients, continuous use of two-drug regimens bortezomib/dexamethasone or lenalidomide/dexamethasone has shown superior overall response and PFS with enhanced tolerability compared with three-drug regimens.
  • New agents for the treatment of MM are under investigation in the relapsed or refractory disease state. As these agents are approved and move to the upfront setting, more exciting and promising results for both the transplant eligible and ineligible patient population will be seen.

Runcie KD & Mark TM. Curr Hematol Malig Rep 2015; 10: 388–394. doi:10.1007/s11899-015-0282-1

Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity

This article provides an overview of the challenges in the care of patients with relapsed/refractory multiple myeloma, current and emerging treatment options, and the possible role of hematopoietic stem cell transplantation.

Summary points
  • The use of modern therapies such as thalidomide, bortezomib, and lenalidomide coupled with upfront high-dose therapy and autologous stem cell transplant (ASCT) has resulted in improved survival in patients with newly diagnosed multiple myeloma (MM).
  • However, patients with relapsed/refractory  MM (RRMM) present a therapeutic challenge as they often have poorer clinical outcomes. These patients have a median survival of only 1.5 years, and their clinical course is typified by decreasing response duration with an increasing number of salvage regimens.
  • Current treatment standards for RRMM include (1) salvage chemotherapy, (2) salvage autologous stem cell transplant (ASCT), (3) allogeneic hematopoietic stem cell transplant (allo-SCT), and (4) post-transplant consolidation/maintenance therapy.
  • Emerging therapies that target different mechanisms of action including immunotherapy, deacetylase inhibitors, monoclonal antibodies, and new proteasome inhibitors are promising and may change the therapeutic landscape in RRMM.
  • Their favorable safety profiles as monotherapy in patients with RRMM will enable combinatorial use with ASCT/allo-SCT to further improve long-term disease control.
  • Improvement in transplant outcomes has re-ignited a debate on the timing and possible role for salvage ASCT and allogeneic stem cell transplant in RRMM.
  • As the treatment options for management of patients with RRMM become increasingly complex, physicians must consider both disease- and patient-related factors in choosing the appropriate therapeutic approach, with the goal of improving efficacy while minimizing toxicity.
  • Enrolment of patients in clinical trials designed to answer unresolved issues in the treatment of patients with RRMM is highly recommended.

Cornell RF & Kassim AA. Bone Marrow Transplant 2016; 51: 479–491. doi: 10.1038/bmt.2015.307

Transplantation for multiple myeloma

This article provides an overview of the challenges in the care of patients with relapsed/refractory multiple myeloma, current and emerging treatment options, and the possible role of hematopoietic stem cell transplantation.

Summary points
  • Multiple myeloma (MM) is a disorder characterized by accumulation of malignant plasma cells in the bone marrow, hypercalcemia, monoclonal protein, and end organ damage.
  • Newer generation proteasome inhibitors, monoclonal antibodies, and novel agents have been approved for patients with MM, which is increasing the life expectancy of the patients. However, hematopoietic stem cell transplantation still remains the cornerstone of treatment.
  • Approximately 24 hours after completion of the preparative chemotherapy, patients undergoing autologous hematopoietic stem cell transplant (AHSCT) receive a reinfusion of peripheral blood progenitor cells followed by a period of pancytopenia. Red blood cell and platelet transfusions are administered as necessary while hematopoietic colony-stimulating factors are used to speed neutrophil engraftment, which occurs by day 10–11. Platelet counts are expected to recover to >20,000 by day 16.
  • For myeloablative allogeneic hematopoietic stem cell transplant (allo-HSCT) the process is similar to AHSCT but myeloablative transplants require that patients receive high-dose chemotherapy with or without total body radiation, followed by donor stem cell infusion.
  • Non-myeloablative-allogeneic transplantation remains investigational and its role needs to be validated in the era of novel agents.
  • Syngeneic allogeneic transplants are from the identical twin donor and only a limited number of syngeneic transplants have been performed in MM.
  • Transplantation helps in early reduction of clonal diversity and increases the likelihood of cure. Long-term follow-up studies show that AHSCT can achieve profound cytoreduction and cure a portion of patients even before the introduction of novel drugs.
  • Novel immune therapeutic agents such as anti-CD38 antibodies, checkpoint blockade inhibitors, cellular therapies, and vaccines will be available soon and will enhance the anti-myeloma response without transplant-associated risks; such strategies will be complimentary and not a replacement for transplant.

Jethava YS & van Rhee F. In: Plasma Cell Dyscrasias. Edited by Roccaro AM & Ghobrial IM. Springer International Publishing, 2016. doi:10.1007/978-3-319-40320-5_13

Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies

Here, Guillerey et al. review the immunological microenvironment in myeloma and highlight the numerous promising immune-targeting strategies approved or in clinical trials for the treatment of myeloma.

Summary points
  • Multiple myeloma (MM) is a tumor localized at various sites within the bone marrow (BM). With over 20,000 new cases diagnosed per year in the United States, MM represents 1% of all cancers and approximately 10% of all hematological malignancies.
  • Early studies established the role of the BM microenvironment in MM pathology but the immune component of this microenvironment has not received full attention until recently.
  • MM is a multistep progressing disease that starts with an asymptomatic premalignant lesion called monoclonal gammopathy of undetermined significance (MGUS) and develops to an escape phase in which active MM can be observed.
  • Several lines of evidence indicate that changes in the immune responses may drive the development from MGUS to MM progression. Along with genetic changes in plasma cells the BM microenvironment is believed to play a crucial role in disease progression to symptomatic myeloma.
  • Therapeutic options such as autologous stem cell transplant, thalidomide, immunomodulatory drugs, and proteasome inhibitors can restore and enhance anti-myeloma immune responses. However, in spite of the clinical success of these therapies, MM remains largely incurable and most patients relapse.
  • Research is currently ongoing to design new therapeutic strategies able to eradicate residual disease, trigger the immune elimination of myeloma cells, and prevent relapse.
  • Harnessing the immune system is an appealing solution and new approaches such as immunotherapy with natural killer cell-based therapies or immune checkpoint modulation hold great promise for MM patients.

Guillerey C, Nakamura K, Vuckovic S, Hill GR, Smyth MJ. Cell Mol Life Sci 2016; 73:1569–1589. doi: 10.1007/s00018-016-2135-z

Multiple myeloma minimal residual disease

This chapter reviews the different levels of remission used to define depth of response in myeloma and their clinical significance, as well as the prognostic value and unique characteristics of minimal residual disease detection.

Summary points
  • Assessment of minimal residual disease (MRD) is becoming standard diagnostic care for potentially curable neoplasms such as some acute leukemias as well as chronic myeloid and lymphocytic leukemia.
  • Multiple myeloma (MM) remains an incurable disease and no clinical trial has randomized MM patients according to their MRD status in order to investigate the role of MRD to individualize therapy.
  • The experience of several cooperative groups using different MRD techniques has indicated that persistence of MRD is always an adverse prognostic feature.
  • It is thus recommended that it would be safer to take clinical decisions based on MRD-positivity rather than on MRD-negativity, since the patchy pattern of bone marrow (BM) infiltration typically observed in MM leads to a degree of uncertainty regarding MRD-negative results: does this guarantee absence of tumor cells or is it the result of a non-representative BM sample due to patchy tumor infiltration?
  • Many studies have shown the value of MRD to evaluate the efficacy of specific treatment phases and therefore to support potential treatment decisions.
  • Several groups have confirmed the added value of MRD in MM, and the time has come to establish the role of baseline risk factors plus MRD monitoring for tailored therapy. This requires the introduction of standardized, highly sensitive, cost-effective, and broadly available MRD techniques in clinical trials.
  • The choice of MRD technology for monitoring will depend on how individual centers’ priorities adjust to the specific advantages that each tool has to offer.

Paiva B, García-Sanz R, & San Miguel JF. In: Plasma Cell Dyscrasias. Edited by Roccaro AM & Ghobrial IM. Springer International Publishing, 2016. doi:10.1007/978-3-319-40320-5_7

Smoldering multiple myeloma: emerging concepts and therapeutics

This review focuses on advances in the smoldering multiple myeloma risk-stratification model and recent clinical trials in this patient population.

Summary points
  • Smoldering multiple myeloma (SMM) is a pre-malignant condition with an inherent risk for progression to multiple myeloma (MM).
  • The 2014 International Myeloma Working Group guidelines define SMM as a monoclonal gammopathy disorder with serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 hours and/or clonal bone marrow plasma cells 10–60% without any myeloma-defining events or amyloidosis.
  • Risk of progression from SMM to MM varies depending on type and degree of monoclonal gammopathy, involvement of light chains, underlying cytogenetic abnormalities, molecular gene expression profile, early radiographical findings, and the duration of SMM.
  • Over the past few years, research advances in SMM have led to the delineation of newer risk factors for progression and identification of a ‘high-risk’ group that would potentially benefit from early treatment.
  • Finding the therapy with maximal benefit and minimal adverse effect will be crucial. Predictive markers for treatment efficacy, utility of high dose chemotherapy with stem cell transplantation, and maintenance therapy are key questions that will be answered in the next few years.
  • The use of imaging, genetic, and other tools may also help physicians to dichotomize SMM patients into those that have a high likelihood of progression and hence need treatment to try and alter the natural history of the disease and those that have a low likelihood of progression who can be managed with observation alone and will most likely not progress to symptomatic myeloma in their lifetime.
  • Research in SMM will be focus on ascertaining the right therapy and its optimal timing. The use of novel MM agents will progress forward into the realm of SMM. Future trials will also look at defining whether early treatment of high-risk SMM would yield the evasive ‘cure’ for MM.

Sundararajan S, Kumar A, Korde N, Agarwal A. Curr Hematol Malig Rep 2016; 11: 102–110. doi: 10.1007/s11899-016-0305-6

Treatment-related symptom management in patients with multiple myeloma: a review

This review discusses current multiple myeloma treatment options, effective symptom management approaches, and practical strategies for supportive care.

Summary points
  • Recent therapeutic advances have significantly improved overall survival in patients with multiple myeloma (MM), with a concomitant increase in susceptibility to disease- and treatment-related symptoms.
  • Current therapeutic regimens for relapsed/refractory MM include proteasome inhibitors (eg, bortezomib, carfilzomib) and immunomodulatory agents (eg, thalidomide, lenalidomide, pomalidomide), alone or in combination with chemotherapy or corticosteroids.
  • Toxicities associated with agents and combination regimens used in the treatment of MM include myelosuppression, venous thromboembolism, peripheral neuropathy, infections, fatigue, gastrointestinal disorders, and/or cardiac events.
  • Treatment-specific tools and clinical assessments can be useful for optimizing dosing and schedule adjustments to increase therapy duration, and implementing supportive care strategies (such as growth factors, transfusional support, intravenous hydration, bisphosphonates, and antiviral therapies) to manage treatment-related symptoms.
  • Effective management of the patient with MM requires knowledge of the disease and of treatment-associated adverse events in addition to preventative measures, supportive care strategies, and management of comorbidities. Patient education and individualized survivorship plans can play a role in achieving maximal patient responses to treatment.
  • Improved survival after MM diagnosis has led to increased patient susceptibility to other diseases and comorbidities due to advanced age, thus optimal symptom management will be important to maximize quality of life for patients in addition to disease control and survival.

Colson K. Support Care Cancer 2015; 23: 1431–1445. doi:10.1007/s00520-014-2552-1