Strictly Clinical

Improving outcomes for patients with multiple myeloma

Over the last decade, progress in multiple myeloma (MM) treatment has extended survival with good quality of life. We’ve increased our understanding of how the genetic features of myeloma tumors influence patient outcomes, and we have new drugs to fight the disease. Although MM remains incurable, new targeted and less toxic therapies are helping many patients manage it as a chronic disease.

MM accounts for about 15% of hematologic cancers. Currently, about 95,000 Americans are living with or in remission from the disease. Median age at diagnosis is 69; MM rarely occurs before age 45. Incidence is almost 60% higher in males than in females and twice as high in blacks as in whites.

Pathophysiology

Although the exact cause of MM is unknown, we know that the disease starts when a change occurs in a single B lymphocyte. When microorganisms invade the body, those B lymphocytes change into plasma cells that make antibodies to help fight infection. MM is a cancer of these plasma cells, which occur primarily in the bone marrow, where they amass and disrupt normal blood cell production.

Normally, genes regulate formation of new cells as the body needs them and regulate cell death when they grow old and nonfunctional. But in MM, abnormal cells make new cells that aren’t needed and don’t die when they get old or damaged. Over time, these malignant cells crowd out normal cells in the bone marrow, invade bone tissue, and spread throughout the body. At diagnosis, about 90% of patients have disease involving multiple sites—hence the term multiple myeloma.

Precursor conditions

MM usually starts as an asymptomatic premalignant stage of plasma cell proliferation termed monoclonal gammopathy of undetermined significance (MGUS). This condition occurs in more than 3% of the population older than age 50 and progresses to MM at a rate of about 1% per year.

Some patients have an intermediate asymptomatic but more advanced premalignant stage called smoldering multiple myeloma (SMM). They have minimal disease with little evidence of progression; instead of early treatment, clinicians may recommend watchful waiting with observation and periodic examinations and imaging tests. While some patients with SMM may not require immediate therapy, they do need careful follow-up. Generally, they’re not treated until symptoms develop. While the risk of progression to active disease is only about 10% annually, most patients eventually progress and require therapy. Therefore, experts recently updated diagnostic guidelines to allow for earlier treatment of SMM, before end-organ damage has occurred, as indicated by the CRAB criteria (discussed below).


Assessment

Some patients may lack symptoms or complain they tire more easily and feel weak. In many cases, the first symptom of MM is bone pain from the effects of myeloma cells on the marrow; fractures may occur from weakened bones. Other early signs may include anemia, recurrent infections, and peripheral neuropathy.

To remember the hallmark clinical features of MM, use the CRAB acronym:

C: Calcium elevation (above 11.5 mg/dL). In about 30% of patients, this manifests as lethargy, confusion, GI distress, or arrhythmias. These features reflect neurologic and cardiac dysfunction.

R: Renal insufficiency (creatinine level above 2 mg/dL). This condition can cause peripheral edema, decreased urine output, and electrolyte imbalances (present in about 50% of patients).

A: Anemia (hemoglobin below 10 g/dL or 2 g below normal). Occurring in nearly 75% of MM patients, anemia causes shortness of breath, dyspnea on exertion, fatigue, and cold intolerance. It reflects immunologic and cardiac dysfunction.

B: Bone disease: In about 80% of patients, bone disease causes lytic lesions, compression or pathological fractures, or osteopenia.

Treatment

Treatment goals are to reduce symptoms, slow disease progression, and prolong remission. Before undertaking aggressive treatment, clinicians and patients must weigh risks against benefits and consider quality of life as the disease progresses.

Most treatment plans include a combination of therapies. Some patients need only supportive care to address anemia, high blood calcium levels, infections, or bone damage. Others receive myeloma-specific therapies to treat disease progression and induce remission. Myeloma-specific therapies include:

  • single or combination drug therapy
  • high-dose chemotherapy with stem cell transplantation
  • radiation therapy for local disease
  • new and emerging drug therapies (as part of a clinical trial).

The approach to treating active MM depends on whether the patient is a candidate for hematopoietic stem cell transplant (HSCT). Eligibility hinges on age, disease progression, impact of disease on activities of daily living, and presence and severity of certain comorbid conditions. Primary treatment regimens include various combinations of such drugs as bortezomib, dexamethasone, cyclophosphamide, doxorubicin, lenalidomide, or thalidomide. (HSCT-eligible patients should avoid melphalan as it may compromise stem cell reserve.) Primary treatment is followed by stem-cell harvest, high-dose therapy chemotherapy, and HSCT. (See Drugs commonly used to treat multiple myeloma.) 

For active MM in patients who aren’t HSCT candidates, primary treatment regimens resemble those used for HSCT candidates and include the same combination therapies with the same drugs. Melphalan can be used as a treatment option in this population. Drugs may be given as single agents, sequentially, or as a combination of drug classes. Sometimes, adding more drugs improves response.

Salvage therapy

Almost all MM patients experience relapses, refractory disease, or both. When preferred therapies fail, various options may be used as salvage therapy. If relapse occurs 6 months after initial therapy, the patient may be retreated with the same primary regimen. Alternatively, different drugs may be used alone or in combination; these drugs may include bortezomib, dexamethasone, cyclophosphamide, doxorubicin, lenalidomide, thalidomide, carfilzomib, cyclophosphamide, vincristine, doxorubicin, high-dose cyclophosphamide, bendamustine, pomalidomide, and vorinostat.

MM patients may experience complications caused by the disease, treatment, or both. For common complications that require early recognition and intervention to improve outcomes and quality of life, see Myeloma complications at a glance.

Other treatments

Like the disease itself, radiation therapy, chemotherapy agents, and immunomodulatory drugs may lead to myelosuppression, causing decreases in red blood cells (RBCs), white blood cells (WBCs), and platelets in the bone marrow. Unless managed effectively, these side effects can disrupt the treatment plan, lower the quality of life, or threaten the patient’s life. If clinicians suspect myelosuppression results from a specific drug therapy, treatment may be withheld or drug dosages may be decreased.

Although a decreased RBC count (manifesting as anemia) is common in MM patients, it also may stem from specific drugs (particularly melphalan, cyclophosphamide, lenalidomide, and pamolinolide), radiation therapy, or HSCT. Management depends on anemia severity and whether the patient has symptoms. In most cases, RBC transfusions are given to patients with hemoglobin values of 8 g/dL or lower. For hemoglobin values of 8 to 10 g/dL, treatment may not be needed (although blood counts and patient status must be monitored). On the other hand, transfusions usually are given if the patient is short of breath or has dyspnea on exertion, fatigue, or cold intolerance. Patients with moderate to severe anemia may receive erythropoietin (a growth factor that stimulates RBC production) instead of blood transfusions. The body takes some time to produce new RBCs, so erythropoietic agents may take 2 to 6 weeks to have an effect.

Neutropenia (WBC reduction) can result from such drugs as melphalan, cyclophosphamide, bortezomib, lenalidomide, and pamolinolide, as well as from radiation therapy. This condition may cause serious infections that call for antibiotic therapy. In some cases, patients need prophylactic antibiotics to prevent infection, especially after high-dose chemotherapy. Some neutropenic patients may receive WBC growth factors, such as filgrastim or pegfilgrastim. In this case, be sure to teach patients about handwashing technique and hygiene to help avoid infection and advise them to receive certain immunizations, such as pneumococcal and influenza vaccines. Caution them not to receive immunizations with live organisms.

Thrombocytopenia (platelet reduction), can result from such drugs as bortezomib and lenalidomide. Excessive bleeding from cuts or injuries may require platelet transfusions or platelet growth factors.

Managing renal dysfunction

MM patients may have serious renal dysfunction. Excretion of large amounts of protein in the urine can cause kidney damage, affecting filtration and the tubules (which aid urine formation). Also, many patients have high blood calcium or uric acid levels, which can damage the kidneys.

In some cases, successful myeloma treatment can improve kidney function and may even restore it to normal. Bisphosphonate therapy using zoledronic acid or pamidronate can reduce blood calcium levels. Patients may need to follow a renal diet and limit fluids to help conserve kidney function. If this diet isn’t effective, they may require dialysis.

Managing bone pain

Myeloma tumor expansion may cause bone pain. Keeping patients on the MM regimen helps reduce tumor spread and related pain. Bone fractures also may cause pain. Many patients require pain medications, such as nonsteroidal anti-inflammatory agents and, in some cases, opioids. Although opioids can cause sedation and constipation, they can be highly effective and, in cancer patients, aren’t associated with a high risk of addiction or dependency.

Because MM patients are at increased risk for bone fractures, bisphosphonate therapy with zoledronic acid or pamidronate may be warranted. Tumors may cause the vertebrae to collapse and press on nerves, causing spinal cord compression; in this case, the patient may have pain radiating from the back. Radiation or kyphoplasty can be effective in treating such compression.

Managing peripheral neuropathy

Peripheral neuropathy may stem from the disease itself or certain anticancer drugs, including oncovin, bortezomib, thalidomide, and lenalidomide. Other problems that can cause or contribute to neuropathy include diabetes, nerve compression stemming from vertebral fractures, and vitamin deficiencies (particularly of folate or vitamin B12). Signs and symptoms may include temporary or ongoing numbness, tingling, burning, coldness, or weakness in the arms or legs. Reducing drug dosages or stopping drugs altogether may reduce symptoms or resolve them completely. Symptomatic treatment with pregabalin or anticonvulsants has shown efficacy as well.

Managing deep vein thrombosis

Standard MM drug therapies, such as thalidomide and lenalidomide, are linked to increased incidence of deep vein thrombosis (DVT) when used in combination with corticosteroids (such as dexamethasone) or liposomal doxorubicin. Other factors that can increase DVT risk include central line use, decreased mobility, recent surgery, smoking, a history of DVT, or a family history of blood-clotting problems. To reduce DVT risk, most newly diagnosed MM patients are prescribed aspirin, coumadin, or low-molecular-weight heparin.

Managing fatigue

One of the most troublesome complaints in MM patients, fatigue can stem from many factors, including disease-related anemia, treatment and medication side effects, physical immobility, sleep disturbances, nutritional deficits, depression, stress, and anxiety. Each patient’s fatigue should be evaluated individually and appropriate management strategies implemented to address problems contributing to fatigue.

Encourage patients to stay active each day and plan rest periods before and after activities, to drink plenty of water, and to eat a well-balanced diet that includes high-protein foods. Recommend nutritional supplements with meals or a snack. Advise patients to get help managing stressful problems or difficult emotions or situations, and to accept offers of help from others. (See Online resources.)

Vital role of the nurse

MM remains a complex disease to diagnose and treat, but recent advances are prolonging survival. Some people are now living with the disease for many years. You can improve patient outcomes and quality of life by gaining a greater understanding of MM and potential complications, learning how to assess the disease, and ensuring early intervention.      

Selected references

American Cancer Society. Cancer Facts and Figures 2016. Atlanta, GA: American Cancer Society; 2016.

www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf

Leukemia and Lymphoma Society. Facts 2014-2015. lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/generalcancer/pdf/facts.pdf

National Comprehensive Cancer Network. NCCN Guidelines Version 2.2015. (September 30, 2014). www.nccn.org/about/news/ebulletin/ebulletindetail.aspx?ebulletinid=418

Tariman J, Faiman B, eds. Multiple Myeloma: A Textbook for Nurses. Pittsburgh, PA: Oncology Nursing Society; 2015.

Yarbro CH, Wujcik D, Gobel BH. Cancer Symptom Management. Burlington, MA: Jones & Bartlett Learning, LLC; 2014.

Kimberly Catania is a clinical nurse specialist in hematology at The Ohio State University Comprehensive Cancer Center, Arthur G. James and Richard J Solove Research Institute, in
Columbus.

 

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One thought on “Improving outcomes for patients with multiple myeloma”

  1. Lynne Brophy says:

    Thank you for this wonderful article. I appreciate the CRAB acronym. Please continue to include these types of scholarly articles.

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