NCCN Guidelines® Insights: Multiple Myeloma, Version 3.2022

Callander, Natalie S.; Baljevic, Muhamed; Adekola, Kehinde; Anderson, Larry D.; Campagnaro, Erica; Castillo, Jorge J.; Costello, Caitlin; Devarakonda, Srinivas; Elsedawy, Noura; Faiman, Matthew; Garfall, Alfred L.; Godby, Kelly N.; Hillengaß, Jens; Holmberg, Leona; Htut, Myo; Huff, Carol Ann; Hultcrantz, Malin; Kang, Yubin; Larson, Sarah; Liedtke, Michaela; Martin, Thomas G.; Omel, James; Sborov, Douglas W.; Shain, Kenneth H.; Stockerl‐Goldstein, Keith; Weber, Donna M.; Berardi, Ryan A; Kumar, Rashmi; Kumar, Shaji

doi:10.6004/jnccn.2022.0002

Cited by 114 publications

(98 citation statements)

References 34 publications

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“…From these findings IMPEDE score and SAVED score were recommended to be utilized as a VTE risk stratification tool. 47 Moreover, they should be employed in prospective studies looking into investigating VTE prophylaxis strategies in MM patients.…”

Section: Thrombo-hemorrhagic Risk Factors and Risk Stratificationmentioning

confidence: 99%

Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an <i>ad hoc</i> expert panel

et al. 2022

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The introduction of new therapeutic agents in multiple myeloma (MM), including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has improved the outcomes of patients but, in parallel, has changed the frequency and epidemiology of thrombotic events. Now, thrombosis is a significant cause of morbidity and mortality in MM patients, and optimal thromboprophylaxis is far from being reached. Moving from the recognition that the above issue represents an unmet clinical need, an Expert Panel assessed the scientific literature and composed a framework of recommendations for improving thrombosis control in patients candidates for active treatment for MM. The Panel generated clinical key questions using the criterion of clinical relevance through a Delphi process. It explored four domains, i.e., thrombotic risk factors and risk stratification, primary thromboprophylaxis, management of acute thrombotic events, and secondary thromboprophylaxis. The issued recommendations may assist hematologists in minimizing the risk of thrombosis and guarantee adherence to treatment in patients with MM candidates to active treatment.

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Section: Thrombo-hemorrhagic Risk Factors and Risk Stratificationmentioning

confidence: 99%

Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an <i>ad hoc</i> expert panel

et al. 2022

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“…The advantages of zoledronic acid (4 mg) include lower mean skeletal morbidity rate, increased median time to first SRE, and reduced risk of developing an SRE compared with pamidronate (90 mg) [ 109 ]. BPs are recommended as standard treatment of MM patients with either osteolytic bone lesions or osteopenia in many current guidelines, including those from the National Comprehensive Cancer Network (NCCN) [ 110 ], the American Society of Clinical Oncology (ASCO) [ 111 ], the Mayo Clinic [ 112 ], the European Society for Medical Oncology (ESMO) [ 113 ], and the International Myeloma Working Group (IMWG) [ 11 ]. Zoledronic acid or pamidronate once monthly, at least for the first 1 to 2 years, is recommended for almost all patients with MM who have evidence of MBD [ 11 , 111 , 112 , 113 ] ( Table 1 ).…”

Section: Current Myeloma-related Bone Disease Treatmentmentioning

confidence: 99%

Pathogenesis and Treatment of Myeloma-Related Bone Disease

Yeh

Hsu

Hsiao

et al. 2022

IJMS

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Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/β-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins are involved and play critical roles in MBD. Currently, bisphosphonate and denosumab are the gold standard for MBD prevention and treatment. As the molecular mechanisms of MBD become increasingly well understood, novel agents are being thoroughly explored in both preclinical and clinical settings. Herein, we will provide an updated overview of the pathogenesis of MBD, summarize the clinical management and guidelines, and discuss novel bone-modifying therapies for further management of MBD.

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“…More recently, the MAIA study including patients ineligible for auto-HSCT due to age or comorbidities showed that adding daratumumab to RD (DRD) led to a 47% and 32% reduction in the risk of progression and death, respectively, compared to RD alone [ 50 ]. Given these results, both VRD and DRD have been established as the preferred therapeutic options for patients with newly diagnosed MM who are not eligible for auto-HSCT [ 51 ].…”

Section: Immunomodulatory Drugs (Imids)mentioning

confidence: 99%

CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma

Barankiewicz

Salomon-Perzyński

Misiewicz-Krzemińska

et al. 2022

Cancers

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Multiple myeloma (MM) is the second most common hematological malignancy with a recurrent clinical course. The introduction of immunomodulatory drugs (IMiDs) was one of the milestones in MM therapy leading to a significant improvement in patients’ prognosis. Currently, IMiDs are the backbone of MM therapy in newly diagnosed and relapsed/refractory settings. It is now known that IMiDs exert their anti-myeloma activity mainly by binding cereblon (CRBN), the substrate receptor protein of the CRL4 E3 ubiquitin ligase (CRL4CRBN) complex. By binding CRBN, IMiDs alter its substrate specificity, leading to ubiquitination and proteasomal degradation of proteins essential for MM cell survival. Following the success of IMiDs, it is not surprising that the possibility of using the CRL4CRBN complex’s activity to treat MM is being further explored. In this review, we summarize the current state of knowledge about novel players in the MM therapeutic landscape, namely the CRBN E3 ligase modulators (CELMoDs), the next generation of IMiDs with broader biological activity. In addition, we discuss a new strategy of tailored proteolysis called proteolysis targeting chimeras (PROTACs) using the CRL4CRBN to degrade typically undruggable proteins, which may have relevance for the treatment of MM and other malignancies in the future.

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NCCN Guidelines® Insights: Multiple Myeloma, Version 3.2022

Cited by 114 publications

References 34 publications

Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an <i>ad hoc</i> expert panel

Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an <i>ad hoc</i> expert panel

Pathogenesis and Treatment of Myeloma-Related Bone Disease

CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma

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