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Current Diagnosis and Management of Multiple Myeloma

Current Diagnosis and Management of Multiple Myeloma

ABSTRACT: The availability of a wide variety of treatments for multiple myeloma allows healthcare providers to tailor treatments to individual patient needs, and has enabled prolonged survival of patients with the disease. Improved understanding of the disease, its treatment options, and potential side effects of therapy has provided unique opportunities for oncology nurses to employ preventive approaches, care strategies, and patient and family education and support over time. Because therapies have been developed that prolong the survival time, people with multiple myeloma are in the position of living with the disease for many years. Additional challenges are presented as healthcare providers develop wellness and quality of life plans of care in the setting of multiple myeloma survivorship. This article will explore the diagnosis, treatment planning, and clinical management of patients with multiple myeloma.

Multiple myeloma (myeloma) is a malignant disorder of the mature B plasma cell.[1] It can be considered a bone marrow disorder, and like leukemia, it prevents normal hematopoiesis and bone marrow function. This results in anemia, thrombocytopenia, and neutropenia. Unique to myeloma is the ability of the myeloma cell to cause problems such as cavitary bone lesions, hypercalcemia, renal failure, and solid plasmacytomas. Normal plasma cells produce normal immunoglobins. In patients with myeloma, abnormal or fragmented immunoglobin chains are secreted, often causing problems due to deposition in the body, particularly in the kidneys.

Multiple myeloma accounts for only about 1.3% of all malignancies in the United States. The American Cancer Society has estimated that about 20,180 new cases of multiple myeloma were diagnosed in the US in 2010, with an estimated 10,650 deaths.[2] The mean age of affected individuals is 62 years for men and 61 years for women, with less than 2% of cases occurring in patients younger than 40 years old. It is the second most common hematologic malignancy in the United States, second only to non-Hodgkin’s lymphoma if all subtypes are considered.[2,3]

Like many cancers, the exact cause of myeloma is not known. Age is a predominant factor. The incidence is higher in men and twice as high in African Americans. Genetic factors are implicated in familial trends.[4]

Myeloma is considered not curable, but treatment advances have improved the survival. Prior to the introduction of melphalan and prednisone in the 1960s, the survival time was less than a year.[5] Autologous stem cell transplant was introduced in the 1980s, further improving survival. The introduction of therapies such as thalidomide (Thalomid), lenalidomide (Revlimid), and bortezomib (Velcade) has also contributed to improved outcome of patients with myeloma in recent years, both in the relapsed-disease setting and at initial diagnosis. An overall survival time of 44.8 months has been reported,[5] and some patients are living up to 10 years from initial diagnosis.[3]

Although approximately 20% of all myeloma patients are diagnosed while they are completely asymptomatic, patients with symptomatic active disease will present with bone pain, fatigue, weight loss, and paresthesias.[6] The most common clinical features at presentation are anemia, lytic bone lesions, renal insufficiency, hypercalcemia, and infection.[7]

Initial Diagnostic Workup for Multiple Myeloma

Initial diagnostic workup includes the items in Table 1. LDH levels help with assessment of tumor cell burden, and the level of beta-2 microglobulin is now considered a standard measure of the myeloma tumor burden.[8] Blood serum analysis also includes quantitative immunoglobulin testing to determine levels of the different types of abnormal antibodies. Assessing the changes and amounts of the immunoglobins in the serum and urine is often helpful in tracking the progression of myeloma disease, although some patients have myeloma that does not secrete abnormal immunoglobins. For those who do, this is often referred to as the “M-spike,” as the monoclonal myeloma protein shows a spike on the plasma electrophoresis test results. The serum free light chain assay has prognostic value for myeloma as well as other plasma cell disorders, including monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, immunoglobulin light chain amyloidosis, and solitary plasmacytoma.[8]

Cytogenetic Abnormalities Associated With “High Risk” Multiple Myeloma
Definition of Multiple Myeloma
Staging Systems for Multiple Myeloma
Myeloma Therapy
European Bone Marrow Transplant (EBMT) and International Myeloma Working Group (IMWG) Response Criteria

Along with the diagnostic staging and patient-specific comorbid conditions (such as renal failure, diabetes, heart conditions, etc), cytogenetic markers may be used on an individual basis to determine the best therapy for a given patient. Cytogenetic tests evaluate whole chromosomes from the nucleus of the cell at the time of mitotic metaphase. This helps to determine the changes in number or structure of chromosomes. One drawback of conventional cytogenetic testing (karyotyping) in myeloma is that the myeloma cells have a low proliferative activity, and it may take up to 2 weeks to receive complete results. Fluorescence in situ hybridization (FISH) is more sensitive but also more expensive.[9–11]

A number of these genetic abnormalities, cytokines, and serum tumor markers have been implicated in the pathogenesis and risk-stratification of myeloma. Although some cytogenetic testing may be done at initial diagnosis, the results are not incorporated into response criteria.[11] Table 2 lists some of the cytogenetic abnormalities that have a negative prognostic implication.

Based on the results of the clinical and laboratory evaluation, patients are initially classified as to whether they have smoldering (asymptomatic) or active (symptomatic) disease. Table 3 highlights definitions of smoldering and active myeloma that may affect treatment decisions.

The first multiple myeloma classification system was published by Durie and Salmon in 1975.[12] The second classification system, the International Staging System for Multiple Myeloma (ISS) is used more commonly in the clinical setting (see Table 4).

Treatment is an induction chemotherapy. This is often a multiagent combination chemotherapy. In selected patients, it is followed by high-dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT). In general, if a patient is a potential HSCT candidate, agents that may later affect stem cell function, such as nitrosoureas or alkylating agents (eg, melphalan or prolonged use of lenalidomide), should be avoided up front. Reduced-intensity or mini-allogeneic transplants have been investigated as therapy following autologous HSCT and as salvage therapy for selected patients.[8] Some patients may be referred to an appropriate clinical trial. In general, different treatment modalities are used over time.

The National Comprehensive Cancer Network (NCCN) has developed clinical guidelines for myeloma treatment.[8] Table 5 describes the common regimens that are used.

Two different response criteria are used to determine the effectiveness of treatment for multiple myeloma. These are described in Table 6.

Myeloma treatment guidelines reflect improvement not only in targeted therapies, but also in supportive care strategies, such as hematopoietic growth factors, blood component support, antibiotics, and antihypercalcemia drugs. Bone disease, renal dysfunction, and other complications such as hypercalcemia, hyperviscosity, and coagulation/thrombosis should be treated with appropriate adjunctive measures.[8]

Nurses have a unique opportunity and challenge to assimilate knowledge about these therapies, disease manifestations, and individual patient comorbidities to collaboratively develop a comprehensive patient care plan with the healthcare team. The section that follows relates to the nursing care of patients with multiple myeloma.


Bone Problems
Skeletal involvement affects nearly 70% of myeloma patients during the course of their disease.[13] Patients with myeloma may have osteolytic or cavitary bone lesions, which may lead to fractures and/or spinal cord compression. Because the myeloma cell produces osteoclast-activating factors (OAFs), there is an upregulation of osteoclast activity. Hypercalcemia is also common.

All patients with documented bone disease should be given a bisphosphonate (pamidronate [Aredia] or zoledronic acid [Zometa]) monthly. It may also be given preventively for patients with osteopenia or osteoporosis.[6,8] The major side effects with prolonged use include renal insufficiency, hypocalcemia, and osteonecrosis of the jaw. Because of the latter, patients should have a comprehensive dental evaluation before receiving any bisphosphonate treatment. They should be instructed to practice good dental hygiene and speak with their oncologists before undergoing any invasive dental procedure.[6] Serum calcium should be routinely monitored; hypercalcemia may be treated with hydration, calcitonin, diuretics, and/or steroids.[8]

Because the osteopenia and lytic lesions place the patient at high risk for fractures, it is crucial that oncology nurses know the number and sites of lytic lesions, to determine whether a patient is at risk for spontaneous pathologic fracture. Orthopedic consultation should be sought for impending or actual long-bone fractures, bony compression of the spinal cord, or any vertebral column instability.

Treatment may include kyphoplasty (vertebroplasty) and/or stabilizing surgery. Percutaneous vertebroplasty is guided by fluoroscopy or CT, with the patient under sedation. An acrylic cement is injected into the malignant bone cavity, thereby strengthening the vertebra(e) and preventing further compression of the myeloma-cavitated body.[14] Prior to the procedure, the patient should have coagulation factors (PT [prothrombin time]/PTT [partial thromboplastin time]) and platelet count checked and corrected if necessary. Nurses need to ensure that the patient and family are informed about any functional limitations that may occur because of pathologic bone lesions. Although even minor movements by the patient alone—such as turning in bed or lifting a shopping bag—can lead to a spontaneous fracture, all healthcare staff need to make sure that the patient is not turned or moved in a way that may contribute to a fracture.

Maintaining and improving physical functioning should be part of the patient’s treatment plan. Exercise training is safe during and after cancer treatment, and it results in improvements in physical functioning, quality of life, and cancer-related fatigue.[15] As with other individuals age 65 years and older, patients with myeloma have particular risk factors related to falls (eg, visual problems, orthostatic hypotension, problems with gait and balance). In 2006, the Centers for Disease Control and Prevention (CDC) estimated that approximately 16% of all US adults in that age group fell at least once, and 31% of those who fell sustained an injury.[16] Assessment of safe mobility should be performed continually, as maximizing balance and strength can reduce the patient’s risk of falls. Exercise prescriptions should be individualized according to the patient’s disease, pretreatment level of aerobic fitness, medical comorbidities, response to treatment, and the immediate or persistent negative effects of treatment that are experienced at any given time.[15]

When recommending activity to patients with myeloma, fracture risk and limitations that may imposed by existing neuropathies, in particular, need to be taken into account. Steroids, a very common component of the treatment plan for myeloma, can cause a wide range of moderate to life-threatening side effects. Those that can affect mobility include proximal myopathy or muscle weakness, weight gain, visual changes, osteoporosis, and osteonecrosis.[17]

At every encounter, nurses should evaluate myeloma patients’ abilities to perform activities of daily living in a safe manner, so that falls and fractures are avoided. The nurse should ensure that appropriate referrals are made to rehabilitation physicians or physical therapists or, minimally, that an activity or exercise program is prescribed.


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