Complications
Occurs in 60% to 70% of patients.[5][6] Treatment of the underlying disease and use of bisphosphonates (e.g., zoledronic acid, pamidronate) are usually sufficient to reduce the pain. Denosumab may be used instead of bisphosphonates, particularly for patients with renal impairment.[175][176][177] In June 2018, the UK Medicines and Healthcare products Regulatory Agency issued a safety alert following a pooled analysis of four phase 3 studies of denosumab in patients with advanced malignancies involving bone.[178] New primary malignancies were reported more frequently among patients receiving denosumab than in those receiving zoledronic acid (cumulative incidence of new primary malignancy at 1 year was 1.1% for denosumab and 0.6% for zoledronic acid). No treatment-related pattern for individual cancers or cancer groupings was identified.
Some patients may require additional pain medication. Avoiding nonsteroidal anti-inflammatory drugs is recommended.
Radiation therapy is sometimes used to treat localized areas where there is bone destruction and pain.
Vertebroplasty and kyphoplasty are options in selected patients with severe refractory pain from pathologic compression fractures.
Pathologic and compression fractures of the vertebral bodies and hypercalcemia are related to osteolytic bone lesions. Plasma cells produce osteoclast-activating factors and osteoblast-inhibiting factors that result in increased bone resorption and osteolytic lesions.
Bisphosphonates (e.g., zoledronic acid, pamidronate) are the standard therapy for MM-related bone disease.[175][176]
[ 
]
Denosumab (a monoclonal antibody that targets the receptor activator of nuclear factor-kappaB ligand [RANKL]) may be used instead of bisphosphonates, particularly for patients with renal impairment.[175][176][177] In June 2018, the UK Medicines and Healthcare products Regulatory Agency issued a safety alert following a pooled analysis of four phase 3 studies of denosumab in patients with advanced malignancies involving bone.[178] New primary malignancies were reported more frequently among patients receiving denosumab than in those receiving zoledronic acid (cumulative incidence of new primary malignancy at 1 year was 1.1% for denosumab and 0.6% for zoledronic acid). No treatment-related pattern for individual cancers or cancer groupings was identified.
Treatment consists of maintaining hydration, and treatment of the underlying MM, as well as inhibition of osteoclastic bone resorption with glucocorticoids and/or bisphosphonates.
Denosumab may be used instead of bisphosphonates, particularly for patients with renal impairment.[175][176][177] In June 2018, the UK Medicines and Healthcare products Regulatory Agency issued a safety alert following a pooled analysis of four phase 3 studies of denosumab in patients with advanced malignancies involving bone.[178] New primary malignancies were reported more frequently among patients receiving denosumab than in those receiving zoledronic acid (cumulative incidence of new primary malignancy at 1 year was 1.1% for denosumab and 0.6% for zoledronic acid). No treatment-related pattern for individual cancers or cancer groupings was identified.
Commonly associated with MM, but the treatment of the underlying MM corrects the anemia. Anemic patients sometimes benefit from erythropoietin (EPO) administration, if baseline serum erythropoietin levels are below 50 units/mL.[224] It is important to ensure that the patient is not iron-deficient before initiating EPO. In general, treatment is started when hemoglobin levels fall <10-11 g/dL.
Cytopenia is linked to tumor infiltration of the bone marrow, renal impairment, and myelosuppressive effects of chemotherapy.
Can be prevented or reduced by the use of growth factors (e.g., granulocyte colony-stimulating factor/filgrastim).
Peripheral neuropathy caused by MM is reported in up to 20% of patients.[230] Symmetric, distal sensory or sensorimotor neuropathy is most common and is associated with axonal degeneration, with or without amyloid deposition. In some cases, neuropathy is associated with monoclonal antibodies directed against peripheral nerve myelin.
Treatment-related neuropathy is common, affecting up to 75% of patients.[230] Neuropathic pain may be treated with medications such as gabapentin and duloxetine.
Patients with MM treated with thalidomide-, lenalidomide-, or pomalidomide-containing regimens are at increased risk for venous thromboembolism (VTE).[231][232]
Use of prophylactic anticoagulant therapy with aspirin, low-molecular-weight heparin, apixaban, or rivaroxaban is recommended with a risk-stratified approach using scoring systems such as IMPEDE or SAVED.[44][233][234][235][236][237][238][239][240]
The certainty of the evidence for the comparative effects of aspirin, vitamin K antagonist, low-molecular-weight heparin, and direct oral anticoagulant on all‐cause mortality, deep vein thrombosis, pulmonary embolism, or bleeding in ambulatory patients with MM is low or very low.[241]
A predictor for an adverse outcome. The causes are often multifactorial and include hypercalcemia, MM kidney, hyperuricemia, toxicity from intravenous urography, dehydration, plasma cell infiltration, pyelonephritis, medications such as nonsteroidal anti-inflammatory drugs, and amyloidosis.
Aggressive hydration and treatment of the underlying MM are the usual measures.[174] Decisions about dialysis are affected by the status of the underlying disease.
Patients with MM are at an increased risk of infections because of the underlying hypogammaglobulinemia and treatments.[69][70]
For patients with newly diagnosed myeloma who are starting treatment, prophylactic levofloxacin for the first 12 weeks of therapy may reduce the risk of febrile episodes and death.[225] This practice could be considered in patients who are at high risk of early mortality. However, it may not be widely adopted given concern over antimicrobial resistance; local antibiotic resistance patterns should be considered.
Hepatitis B virus (HBV) reactivation has been reported in patients with MM receiving immunomodulatory therapy (e.g., daratumumab [some fatal cases], carfilzomib). All patients should be screened for HBV as clinically indicated.[226] Patients already receiving immunomodulatory therapy and for whom HBV serology is unknown should also be tested for HBV. Patients with positive HBV serology should be monitored for clinical and laboratory signs of HBV reactivation during and after treatment. Treatment should be stopped in patients with HBV reactivation, and experts in the treatment of HBV should be consulted. Resumption of immunomodulatory therapy in patients whose HBV reactivation is adequately controlled should be discussed with physicians who have expertise in managing HBV.[227][228]
Antiviral prophylaxis with acyclovir is indicated for patients who are seropositive for herpes simplex virus or varicella zoster virus.[214] Given the risk for herpes zoster reactivation with therapies such as proteasome inhibitors (e.g., carfilzomib, bortezomib) and monoclonal antibodies (e.g., daratumumab, isatuximab, elotuzumab), antiviral prophylaxis with acyclovir should be given for the duration of treatment and continued for at least 3-6 months after completion of treatment.[214]
Streptococcus pneumoniae and Haemophilus influenzae infections usually occur early and typically during response to chemotherapy.
Healthcare providers should ensure that patients receive all appropriate vaccinations: in particular, the influenza, pneumococcal, and recombinant zoster vaccinations.[214]
Prophylaxis for Pneumocystis jirovecii pneumonia may be considered in patients with MM with particular risk: for example, those who have relapsed or refractory disease receiving high doses of dexamethasone (doses ≥40 mg/day for 4 days per week).[214]
Gram-negative infections occur in refractory, advancing disease, in the setting of previous antibiotic therapy, instrumentation, immobilization, colonization with hospital flora, and azotemia.
Patients should be taught to take the onset of fever seriously and seek immediate medical attention.
Patients who are hypogammaglobulinemic with recurrent infections or who have survived a serious infection may benefit from monthly infusions of intravenous immune globulin (IVIG).[214]
Characterized by spontaneous bleeding, headache, and neurologic and visual disorders. It is associated with IgM paraproteins, but also with IgG3 subclass and IgA. Treatment includes plasmapheresis, which reduces both M-protein concentration and serum viscosity, and MM-specific therapy.
Older patients with MM are at increased risk of cardiovascular disease, mainly cardiac ischemia and/or congestive heart failure due to myocardial infiltration with amyloid, causing dilated or restrictive cardiomyopathy, hyperviscosity syndrome, and/or anemia.
Treatment-related cardiac failure is associated with carfilzomib treatment.[229] Appropriate risk factor management should be provided to older patients and patients with underlying risk factors.
Patients with MM are also susceptible to high-output congestive heart failure of unclear etiology.
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