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Treatment of the complications of multiple myeloma
Author:
S Vincent Rajkumar, MD
Section Editor:
Robert A Kyle, MD
Deputy Editor:
Rebecca F Connor, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Aug 01, 2016.

INTRODUCTION — Patients with multiple myeloma frequently develop complications related to their disease, including hypercalcemia, renal insufficiency, infection, and skeletal lesions, which require specific treatment in addition to therapy directed at the malignant clone [1,2]. Some of these problems are discussed in detail elsewhere within UpToDate, but will be briefly reviewed here.

The importance of these complications was highlighted in a study of death within 60 days of diagnosis in patients with myeloma entering onto the United Kingdom's Medical Research Council (MRC) trials. The incidence of early death was 10 percent, with the most common contributors being bacterial infection (50 percent) and renal failure (28 percent) [3].

Treatment of the complications of multiple myeloma will be reviewed here. The uses of chemotherapy and hematopoietic cell transplantation in the treatment of multiple myeloma are discussed separately, as is the diagnosis of multiple myeloma. (See "Overview of the management of multiple myeloma" and "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma".)

HYPERCALCEMIA — Hypercalcemia is present in over 10 percent of patients with myeloma at the time of diagnosis and may require emergent treatment. Patients with hypercalcemia may be asymptomatic or complain of a variety of symptoms such as anorexia, nausea, vomiting, polyuria, polydipsia, increased constipation, weakness, confusion, or stupor. Hypercalcemia can also contribute to the development of renal insufficiency. (See "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma", section on 'Hypercalcemia' and "Clinical manifestations of hypercalcemia".)

In most patients with myeloma the diagnosis of hypercalcemia does not require measurement of the ionized calcium. However, if a patient presents with an elevated serum calcium level but no associated symptoms, the ionized calcium should be measured to confirm hypercalcemia prior to the initiation of treatment since rarely the monoclonal protein binds to calcium [4]. The treatment of hypercalcemia depends upon the calcium level, the rapidity with which it developed, and the patient's symptoms. In general, the following approach may be considered:

Hydration, preferably with isotonic saline, plus either dexamethasone as part of myeloma therapy or prednisone (1 mg/kg per day) is effective in most cases of mild hypercalcemia (eg, serum calcium <12 mg/dL).

In moderate to severe hypercalcemia (eg, serum calcium >14 mg/dL), treatment includes hydration, corticosteroids, and a bisphosphonate such as zoledronic acid or pamidronate. Calcitonin is used if rapid reduction of calcium levels is needed or if patients are refractory to bisphosphonates alone.

Extremely severe hypercalcemia (eg, >18 mg/dL) may require hemodialysis in addition to the measures outlined above.

Typically, zoledronic acid is administered intravenously at a dose of 4 mg over 15 minutes, and pamidronate is given intravenously at a dose of 60 to 90 mg over at least two hours. The dose of zoledronic acid needs to be reduced in patients with renal failure. In patients who present with acute and severe renal failure, pamidronate is preferable since the dosing of zoledronic acid may be difficult to determine in the acute setting. Further details regarding the treatment of hypercalcemia are presented separately. (See "Treatment of hypercalcemia".)

RENAL INSUFFICIENCY — Renal insufficiency, which can be acute or insidious in onset, occurs in approximately one-half of patients with multiple myeloma. A variety of etiologic mechanisms may be involved, including those related to the excess production of monoclonal light chains (light-chain cast nephropathy), deposition of intact light chains causing nephrotic syndrome (light chain deposition disease), light chain amyloidosis, hypercalcemia, radiocontrast media-induced acute renal failure (usually due to dehydration in the presence of Bence Jones proteinuria) and, infrequently, hyperuricemia. (See "Epidemiology, pathogenesis, and etiology of kidney disease in multiple myeloma and other monoclonal gammopathies".)

All patients with multiple myeloma, especially those with large amounts of urinary free light chain excretion, should take measures to minimize renal damage. These include the avoidance of nephrotoxins such as aminoglycosides and NSAIDs and the maintenance of hydration by drinking enough fluids to produce 3 liters of urine/day. Certain medications frequently used for the treatment of multiple myeloma or its complications (eg, lenalidomide, zoledronic acid) may require dose adjustment for renal insufficiency or may contribute to renal failure. The treatment of renal insufficiency is directed at the underlying cause, and is discussed elsewhere as is the use of plasmapheresis and/or hemodialysis in the setting of acute renal failure. (See "Epidemiology, pathogenesis, and etiology of kidney disease in multiple myeloma and other monoclonal gammopathies" and "Treatment and prognosis of kidney disease in multiple myeloma and other monoclonal gammopathies".)

The presence of acute renal failure due to light-chain cast nephropathy may also have impact on the choice of initial induction therapy. A dexamethasone-containing triplet regimen, such as bortezomib, cyclophosphamide, plus dexamethasone (VCD) or bortezomib, thalidomide plus dexamethasone (VTD) may be preferred [5]. VCD and VTD do not need dose reductions for renal failure; weekly doses of the drugs used in these regimens can be adjusted based on counts and other adverse effects. Usually, renal function improves with therapy. Even if it does not, autologous hematopoietic cell transplantation can be performed, but at greater morbidity and mortality in patients with renal insufficiency. (See "Overview of the management of multiple myeloma", section on 'Renal function' and "Selection of initial chemotherapy for symptomatic multiple myeloma".)

INFECTION — Patients with myeloma are at increased risk for infection [6,7]. The rate of infections is highest in the first three to four months of induction therapy and in the setting of relapsed disease [3,7]. Factors that contribute to the increased risk of infection include impaired lymphocyte function, suppression of normal plasma cell function, hypogammaglobulinemia, and chemotherapy induced neutropenia. Pneumonias and urinary tract infections account for the majority infections with Streptococcus pneumoniae, Haemophilus influenza, and Escherichia coli being the most common organisms.

Prophylaxis — Preventative measures that may decrease the rate of infection among patients with myeloma include the use of vaccines, prophylactic antibiotics or antivirals, and intravenous immunoglobulin.

Patients with myeloma should have yearly influenza vaccines and a single pneumococcal vaccine at the time of diagnosis. Although the antibody response is reduced in many myeloma patients [8-10], an individual may mount a suboptimal response and still obtain a benefit. Furthermore, there is no evidence that influenza or pneumococcal vaccination is associated with a higher risk of reaction compared to a normal population. Antibody response to pneumococcal vaccination may be suboptimal and prolonged penicillin prophylaxis for pneumococcus should be administered if recurrent pneumococcal infections occur. (See "Prevention of sepsis in the asplenic patient".)

The use of prophylactic antibiotics is controversial. A prospective study of the value of antimicrobial prophylaxis has completed accrual and results are pending. In clinical practice, we administer routine antibiotic prophylaxis with either a fluoroquinolone (eg, levofloxacin 500 mg daily) or trimethoprim-sulfamethoxazole (TMP-SMX) (eg, 80/400 mg once daily or 160/400 mg every other day) during the first three to four months of chemotherapy. In general, TMP-SMX should be avoided in patients receiving thalidomide or lenalidomide therapy due to increased risk of serious skin toxicity; in these patients a fluoroquinolone is preferable. In addition, for all patients receiving bortezomib, we administer antiviral prophylaxis (eg, acyclovir 400 mg twice daily or valacyclovir 500 mg once daily) because of the increased risk of herpes zoster (varicella zoster reactivation) with this agent. (See "Treatment of relapsed or refractory multiple myeloma", section on 'Bortezomib'.)

The decision to administer prophylactic antibiotics at least in the first few months of initial therapy is based upon the high risk of infections in this setting, as well as the results of a small prospective, randomized trial of 54 patients with previously untreated multiple myeloma randomly assigned to treatment with TMP-SMX (160/800 mg PO BID) or placebo for the first two months of induction chemotherapy, which typically included melphalan and prednisone [11]. When compared with patients who were assigned to observation, patients assigned to TMP/SMX had significantly fewer bacterial infections (11 versus 2 patients) and severe infections (8 versus 1 patient) in the first three months. The need for prophylactic antibiotics in the setting of other myeloma therapies (eg, thalidomide, lenalidomide) is less clear.

Intravenous immune globulin (IGIV, IVIG) may be helpful in selected patients who have recurrent, serious infections despite the use of prophylactic antibiotics. (See "Overview of the management of multiple myeloma", section on 'Prevention and management of complications' and "Immune globulin therapy in primary immunodeficiency", section on 'Efficacy' and "Immune globulin therapy in primary immunodeficiency", section on 'Administration and dosing'.)

Treatment — Patients with multiple myeloma suspected of having an infection should be treated promptly (after obtaining appropriate cultures of blood, urine, chest x-ray, etc.) with empiric antibiotics covering encapsulated bacteria and gram negative microorganisms chosen according to the flora and resistance patterns seen at the institution. (See "Overview of neutropenic fever syndromes" and "Diagnostic approach to the adult cancer patient with neutropenic fever" and "Treatment and prevention of neutropenic fever syndromes in adult cancer patients at low risk for complications".)

Patients with neutropenic fever after chemotherapy may be candidates for prophylactic myeloid growth factors (colony stimulating factors) with subsequent chemotherapy cycles. (See "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation", section on 'Secondary prophylaxis'.)

SKELETAL LESIONS — Skeletal lytic lesions leading to bone pain are present at the time of diagnosis in approximately 60 percent of patients with myeloma and up to 20 percent may have osteopenia. A roentgenographic survey including the skull, spine, pelvis, humeri, and femora is a key component in the diagnosis of myeloma and should be routinely repeated at six-month intervals to monitor for the development of skeletal lesions. Imaging with additional plain films, positron emission tomography (PET), PET/CT (computed tomography), and/or magnetic resonance imaging (MRI) is indicated in patients with unexplained bone pain and if pain develops at new sites. (See "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma", section on 'Imaging'.)

Avascular necrosis of the femoral and/or humeral heads is a rare and usually asymptomatic complication during the treatment of multiple myeloma [12]. Cumulative dexamethasone dose, male sex, and younger age increase this risk.

Vertebral compression fractures are common and can result in decreased total lung capacity and changes in the weight-bearing patterns of the spine potentially leading to more fractures.

Prevention of skeletal events — Skeletal lesions can result in bone pain, pathologic fractures, and spinal cord compression. All patients with myeloma should be encouraged to be as active as possible in order to maintain bone density while avoiding activities with an excessive risk of trauma. (See "Prevention of osteoporosis".)

Patients with one or more lesions on skeletal radiographs and those with osteopenia should be given bisphosphonate therapy, which significantly reduces the number of skeletal events (eg, pathologic fracture, irradiation of or surgery on bone, and spinal cord compression). This subject is discussed in depth separately. (See "The use of osteoclast inhibitors in patients with multiple myeloma".)

The most important complications of prolonged bisphosphonate therapy are acute renal failure (more often with zoledronic acid), albuminuria (mainly related to pamidronate) and osteonecrosis of the jaw. If these complications occur, either the dose or the frequency of bisphosphonate administration should be decreased or the agent discontinued. (See "Risks of therapy with bone antiresorptive agents in patients with advanced malignancy".)

Denosumab is a monoclonal antibody to RANKL (receptor activator of nuclear factor-kappaB ligand) that is used for the treatment of osteoporosis and for the management of bone metastases in the setting of a solid tumor. Randomized phase III trials have compared the efficacy of denosumab versus zoledronic acid in patients with bone lesions in the setting of multiple myeloma or solid tumors [13,14]. As an example, a phase III trial of 1776 patients with metastatic bone lesions due to multiple myeloma or non-breast, non-prostate solid tumors randomly assigned therapy to denosumab or zoledronic acid [13]. Denosumab and zoledronic acid resulted in similar times to first on-study skeletal-related event and similar survival rates for the group as a whole. However, a post-hoc subset analysis of the 180 patients with multiple myeloma noted higher mortality among those assigned to denosumab therapy (Hazard ratio 2.26; 95% CI 1.13 to 4.50). The suggestion of inferior survival among patients with multiple myeloma treated with denosumab led the US Food and Drug Administration to approve the use of denosumab in patients with bone metastases from solid tumors, but not multiple myeloma. This is discussed in more detail separately. (See "Mechanisms of bone metastases", section on 'Multiple myeloma' and "Denosumab for osteoporosis" and "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors", section on 'Denosumab'.)

Treatment of fractures — Pathologic fractures or impending fractures of long bones require stabilization with an intramedullary rod. Although the decision to stabilize lytic lesions is made by an orthopedic surgeon and depends in part upon the location of the lesions, a usual rule of thumb is that if there is 50 percent or more destruction of cortical bone thickness, surgical fixation is required. (See "Evaluation and management of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Local treatment'.)

Vertebral fractures may benefit from the intralesional injection of a methyl methacrylate cement with kyphoplasty or vertebroplasty. (See 'Kyphoplasty and vertebroplasty' below.)

Pain control

Pharmacologic therapy — Analgesics and analgesic adjuvants, in combination with chemotherapy, can usually control the bone pain from lytic lesions. (See "Cancer pain management with opioids: Optimizing analgesia" and "Cancer pain management: Use of acetaminophen and nonsteroidal antiinflammatory drugs" and "Cancer pain management: Adjuvant analgesics (coanalgesics)".)

Kyphoplasty and vertebroplasty — Vertebroplasty involves the percutaneous injection of bone cement (methyl methacrylate) under fluoroscopic guidance into a collapsed vertebral body (VB). Kyphoplasty is a technique that involves the introduction of inflatable bone tamps (KyphX Xpander Balloon, Kyphon, Inc.) into the VB [15]. Once inflated, the bone tamps restore the height of the VB, while creating a cavity that can be filled with viscous bone cement. Kyphoplasty is significantly more expensive than vertebroplasty. The choice between kyphoplasty and vertebroplasty is best dictated by the expertise of the practitioner at each institution [16]. (See "Osteoporotic thoracolumbar vertebral compression fractures: Clinical manifestations and treatment", section on 'Vertebral augmentation procedures (vertebroplasty and kyphoplasty)'.)

Kyphoplasty and vertebroplasty have been associated with pain relief in prospective trials in patients with myeloma [17-20]:

An international, non-blinded trial randomly assigned treatment with kyphoplasty versus non-surgical management in 134 patients with cancer (37 percent with myeloma) and painful vertebral body compression fractures [21]. In an intention-to-treat analysis, kyphoplasty resulted in a decrease in a back-specific disability measurement at one month. In addition, kyphoplasty was associated with a significantly lower percentage of patients requiring walking aids (46 versus 25 percent), bracing (22 versus 2 percent), bed rest (46 versus 23 percent), and medications of any kind (82 versus 52 percent).

In a prospective, uncontrolled study, 55 consecutive kyphoplasty procedures were performed in 18 patients with osteolytic VB compression fractures due to myeloma [17]. Significant improvements in pain, physical function, vitality, and social functioning were noted. Pain relief was seen in 80 percent. On average, 34 percent of VB height lost at the time of fracture was restored by this procedure, with no major complications. Asymptomatic cement leakage was noted in 2 of the 55 levels treated.

Another report evaluated kyphoplasty and vertebroplasty in a consecutive group of 21 patients with myeloma and 35 with other primary malignancies, all of whom suffered intractable spinal pain secondary to VB fractures [18]. Marked or complete pain relief was achieved in 84 percent; no patient's pain was made worse and there were no deaths or procedure-related complications. Reductions in pain scores remained significant up to one year following the procedures. The mean percent of restored vertebral body height following kyphoplasty was 42 ± 21 percent. Asymptomatic cement leakage was noted following vertebroplasty or kyphoplasty in 9 and zero percent of cases, respectively.

These procedures have never been tested in a blinded trial in myeloma. Two randomized trials of vertebroplasty versus sham vertebroplasty for painful osteoporotic vertebral fractures demonstrated no benefit to vertebroplasty [22,23]. Patients assigned to vertebroplasty and those assigned to sham vertebroplasty demonstrated similar improvements in pain at night and rest, physical functioning, quality of life, and perceived improvement.  

In general, the choice between vertebroplasty and kyphoplasty depends on the expertise of the physician performing the procedure. Local radiation therapy is rarely needed after these procedures except in rare cases in which the patient has myeloma refractory to systemic therapy.

Short-term complications occur predominantly due to extravasation of the cement and may include increased pain and damage from heat or pressure to the spinal cord or nerve roots, and rarely cement embolization. Patients thought to be most likely to benefit are those who have pain that anatomically correlates to the area of fracture and is most severe in the upright position (eg, standing or walking) and decreases in the reclining position.

Radiation — Up to 40 percent of patients with myeloma will require radiation to control disease at some point in their disease course [24]. Common indications for radiation therapy include:

Pain control of lytic lesions that are refractory to systemic therapy.

Treatment of spinal cord compression from plasmacytoma. (See 'Cord compression' below.)

Primary treatment of solitary plasmacytoma. (See "Diagnosis and management of solitary plasmacytoma of bone" and "Diagnosis and management of solitary extramedullary plasmacytoma".)

Post-surgical radiation after stabilization of impending fractures is rarely needed [25]. Extensive radiation should be avoided because it can reduce bone marrow reserve, compromise future chemotherapy, and may prevent a future autologous stem cell procedure. Most patients can get equally rapid pain relief and reduction in tumor mass with systemic therapy for myeloma. The dose of radiation used varies according to the clinical situation. Palliation of lytic bone lesions may be accomplished with 20 to 30 Gy administered in 5 to 10 fractions while higher doses are required for the treatment of solitary plasmacytoma (in which the intent is curative) or spinal cord compression [26]. Whether radiation is more effective when given in conjunction with chemotherapy is unclear [27]. (See 'Cord compression' below.)

There are limited data regarding the ideal dose of palliative radiation for bone lesions. A retrospective single institution study of 101 patients administered palliative radiation to 306 symptomatic bone sites reported at least partial symptom relief in 98 percent of sites receiving 10 or greater Gy of radiation with no dose response demonstrated [27]. A minority of sites had complete symptom control (26 percent).

Cord compression — Spinal cord compression from an extramedullary plasmacytoma or retropulsed bone should be suspected in patients with severe back pain, weakness, or paresthesias of the lower extremities, or bladder or bowel dysfunction or incontinence. Magnetic resonance imaging (MRI) or computed tomographic (CT) myelography of the entire spine must be performed immediately if this complication is suspected. (See "Clinical features and diagnosis of neoplastic epidural spinal cord compression, including cauda equina syndrome".)

Prompt diagnosis and immediate treatment are critically important in the preservation of neurological function in patients with spinal cord compression. The goals of treatment include pain control, avoidance of complications, and the preservation or improvement of neurologic functioning. In patients with neurologic symptoms directly due to cord compression, radiation therapy is given along with dexamethasone, and up to half of patients may have improvement of motor function with radiotherapy with longer fractionation schedules providing better relief [28]. Systemic therapy with regimens such as bortezomib, cyclophosphamide, dexamethasone (VCD) or bortezomib, thalidomide, dexamethasone (VTD) work rapidly and can be used instead of radiation in selected patients if there is minimal neurologic deficit. Surgical decompression is necessary only if the neurologic deficit does not improve or if the compression is due to retropulsed bone. Details regarding the treatment of neoplastic spinal cord compression are presented separately. (See "Treatment and prognosis of neoplastic epidural spinal cord compression, including cauda equina syndrome".)

ANEMIA — The vast majority (97 percent) of patients with myeloma will have anemia (hemoglobin ≤12 g/dL) at some time during the course of the disease. The initial evaluation of anemia in a patient with myeloma should include a search for common causes of anemia in patients without myeloma (eg, iron or vitamin deficiencies). (See "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma", section on 'Anemia' and "Approach to the adult with anemia".)

The treatment of anemia associated with myeloma depends upon the severity of the anemia, the presence or absence of symptoms related to anemia, and whether the patient is undergoing active chemotherapy. Patients with significant symptoms should be considered for red blood cell transfusion. If a transfusion is indicated, irradiated, leukoreduced cross-matched red cells are preferred. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult".)

The decision to use erythropoiesis-stimulating agents (ESAs) for anemia in multiple myeloma is based upon a number of factors, including stage of disease, response to anti-myeloma therapy, serum erythropoietin levels, cost, and reimbursement policies (eg, need for physician administration). In addition, the use of ESAs is a risk factor for the development of venous thromboembolism among patients with myeloma, especially those treated with thalidomide [29]. In patients with newly diagnosed myeloma, induction chemotherapy with a good disease response is usually associated with a prompt improvement in hemoglobin levels, and it is better to avoid the use of ESAs. ESAs are generally reserved for patients receiving chemotherapy with a hemoglobin level of 10 g/dL or less [30]. The typical dosage is erythropoietin 40,000 units once a week or darbepoetin 200 micrograms every two to three weeks. Darbepoetin has an advantage when physician administration is required. More information on the ASH/ASCO guidelines and suggested starting doses can be found elsewhere. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer", section on 'Overview of treatment options for anemia in cancer patients'.)

Randomized placebo-controlled trials have shown that symptomatic anemia during the plateau phase of multiple myeloma is often improved by the administration of erythropoietin (EPO) [31-33]. In one randomized trial, 145 patients with multiple myeloma and a hemoglobin concentration <11 g/dL were treated with either 150 units/kg of EPO or a matching volume of placebo subcutaneously three times a week for 12 weeks [33]. The dose was doubled at week four if the hemoglobin response was inadequate.

During the double-blind phase of the study, patients receiving EPO had a significantly lower incidence of transfusion (28 versus 47 percent) and larger increase in hemoglobin concentration (1.8 versus 0.0 g/dL). During the open label portion of the trial, patients initially receiving placebo who were switched to EPO had a mean increase in hemoglobin concentration of 2.4 g/dL.

HYPERVISCOSITY SYNDROME — Occasional patients with multiple myeloma develop the hyperviscosity syndrome. This syndrome is characterized by oronasal bleeding, blurred vision, neurologic symptoms, confusion, and heart failure. Serum viscosity measurements do not correlate well with symptoms or the clinical findings. Plasmapheresis promptly relieves the symptoms and should be performed regardless of the viscosity level if the patient is symptomatic [34]. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)

THROMBOSIS — Patients with multiple myeloma or the precursor lesion monoclonal gammopathy of undetermined significance (MGUS) have an increased incidence of venous thromboembolism (VTE). In addition, a few studies have suggested an increased risk of arterial thromboembolism (ATE) in these populations as manifested by stroke, transient ischemic attack, myocardial infarction, or symptomatic peripheral artery disease. These increased rates appear to be both a result of the malignancy itself and the therapy given (eg, thalidomide or lenalidomide-based regimens).

A population-based study of over 4 million patients receiving care at US Veterans Affairs hospitals reported rates of VTE among patients with MM or MGUS of approximately 8.7 and 3.1 cases per 1000 person-years, respectively [35].

Population-based data from Sweden comparing persons with MM or MGUS with matched controls demonstrated that patients with MM and MGUS had increased risks of VTE and ATE in the first 10 years after diagnosis [36]:

The increase in risk of VTE was highest for patients with MM in the first year after diagnosis (hazard ratio [HR] 7.5, 95% CI 6.4-8.9).

Patients with MM also had an increased risk of ATE in the first year (HR 1.9, 95% CI 1.8-2.1).

Patients with MGUS demonstrated increased risks of VTE and ATE, but the magnitude of effect was smaller.

A prospective trial in 195 consecutive patients with newly diagnosed MM treated with three cycles of chemotherapy followed by high dose melphalan and autologous hematopoietic cell transplantation reported a higher than expected frequency of ATE [37]. Induction chemotherapy included doxorubicin and dexamethasone plus either vincristine (VAD), thalidomide (TAD), or bortezomib (PAD). Eleven patients developed ATE, six of which occurred during induction chemotherapy.

Issues related to the treatment of VTE, the risk of VTE with thalidomide analogs, and the use of VTE prophylaxis with thalidomide analogs are presented separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults" and "Overview of the treatment of lower extremity deep vein thrombosis (DVT)" and "Thrombotic complications following treatment of multiple myeloma with immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide)".)

NEUROPATHY — Patients with multiple myeloma can develop peripheral neuropathy related to the disease itself or as a toxicity of treatment (eg, thalidomide, bortezomib) [30,38]. When it occurs, the painful sensory neuropathy can interfere with quality of life and with performance of activities of daily living, and it may require dose modification and/or treatment discontinuation. This is discussed in more detail separately. (See "Overview of neurologic complications of non-platinum cancer chemotherapy", section on 'Bortezomib' and "Overview of neurologic complications of non-platinum cancer chemotherapy", section on 'Thalidomide and related agents'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Plasma cell dyscrasias" and "Society guideline links: Epidural spinal cord compression".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Multiple myeloma (The Basics)")

Beyond the Basics topics (see "Patient education: Multiple myeloma symptoms, diagnosis, and staging (Beyond the Basics)" and "Patient education: Multiple myeloma treatment (Beyond the Basics)")

SUMMARY — Common complications of multiple myeloma include hypercalcemia, renal insufficiency, infection, skeletal lesions, and anemia. Less common complications include venous thromboembolism and the hyperviscosity syndrome.

Hypercalcemia – Patients with hypercalcemia may be asymptomatic or present with anorexia, nausea, vomiting, polyuria, polydipsia, constipation, weakness, confusion, or stupor. The treatment of hypercalcemia depends upon the calcium level, the rapidity with which it developed, and the patient's symptoms. Emergent treatment with hydration, glucocorticoids, bisphosphonates, and/or hemodialysis/calcitonin is indicated for symptomatic patients. (See 'Hypercalcemia' above and "Treatment of hypercalcemia".)

Renal insufficiency – All patients with multiple myeloma should take measures to minimize renal damage (eg, avoid nephrotoxins such as aminoglycosides and NSAIDs and maintain adequate hydration). Many medications used for myeloma require dose adjustment for renal insufficiency (eg, lenalidomide, zoledronic acid). Treatment of renal insufficiency is directed at the underlying cause. (See 'Renal insufficiency' above and "Treatment and prognosis of kidney disease in multiple myeloma and other monoclonal gammopathies".)

Infection – Prophylactic measures that may minimize infection in patients with myeloma include yearly influenza vaccines, pneumococcal vaccine at the time of diagnosis, prophylactic antibiotics during the first months of induction chemotherapy, and intravenous immune globulin for selected patients who have recurrent, serious infections. Patients suspected of having an infection should be treated promptly with empiric antibiotics covering encapsulated bacteria and gram negative microorganisms. (See 'Infection' above and "Immunizations in adults with cancer" and "Treatment and prevention of neutropenic fever syndromes in adult cancer patients at low risk for complications".)

Skeletal lesions – Physical activity should be encouraged in order to maintain bone density, but requires adequate pain control. Patients with one or more lesions on skeletal radiographs and those with osteopenia are candidates for bisphosphonate therapy to prevent skeletal events. Pathologic fractures or impending fractures of long bones require stabilization with an intramedullary rod. Vertebral fractures may benefit from kyphoplasty or vertebroplasty. Most pain related to lytic lesions can be controlled with the combination of analgesics and active myeloma chemotherapy. Spinal cord compression is a clinical emergency and should be suspected in patients with severe back pain, weakness, or paresthesias of the lower extremities, or bladder or bowel dysfunction or incontinence. (See 'Skeletal lesions' above and "Treatment and prognosis of neoplastic epidural spinal cord compression, including cauda equina syndrome".)

Anemia – The treatment of anemia associated with myeloma depends upon the severity of the anemia, the presence or absence of symptoms related to anemia, and whether the patient is undergoing active chemotherapy. Patients with significant symptoms should be considered for red blood cell transfusion. Erythropoiesis-stimulating agents are generally reserved for patients receiving chemotherapy with a hemoglobin level of 10 g/dL or less. (See 'Anemia' above and "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer".)

Neuropathy – Patients with multiple myeloma can develop peripheral neuropathy related to the disease itself or as a toxicity of treatment (eg, thalidomide, bortezomib). When it occurs, the painful sensory neuropathy can interfere with quality of life and with performance of activities of daily living, and it may require dose modification and/or treatment discontinuation. (See "Overview of neurologic complications of non-platinum cancer chemotherapy", section on 'Bortezomib' and "Overview of neurologic complications of non-platinum cancer chemotherapy", section on 'Thalidomide and related agents'.)

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