Multiple Myeloma

Course #30713 - $50 • 10 Hours/Credits


Self-Assessment Questions

    1 . Which tumor marker is identified when a definitive diagnosis of multiple myeloma is established?
    A) Bence Jones proteinuria
    B) Tamm Horsfall mucoprotein
    C) Vascular endothelial growth factor
    D) Macrophage inflammatory protein 1α

    HISTORY OF THE DISEASE

    As early as 1844 the as-yet unidentified disease of multiple myeloma was documented by descriptions of fragile soft bones ("mollities and fragilitas ossium") [4,5]. Building on the discoveries of British physician William Macintyre, who noted that unusual proteins in urine also contributed to this disease, Dr. Bence Jones researched these findings even further, publishing his discoveries in 1848. This was undoubtedly momentous in medical history; Bence Jones proteinuria, or light chains, subsequently emerged as the first tumor marker on record [6]. As research continued, identification of lesions in bone from the infiltration of multiple plasma cells signified a more complex disease process. By 1873, this disease was officially termed multiple myeloma [7]. Moving into the early 1900s, x-ray imaging revealed lytic lesions from bone destruction. Evidence pointed to the bone marrow itself as the producer of plasma cells capable of destroying the bone. Improved technology coupled with refined laboratory testing of serum and urine and advances in bone marrow aspirations and biopsies over the next 50 years yielded results. Immunoglobulins (Ig) were classified by immunoelectrophoresis. In 1956, Bence Jones proteins were subtyped as kappa and lambda, so named in honor of the researchers Korngold and Lipari [8].

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    2 . The first measures of success with melphalan as first-line treatment for multiple myeloma were reported in
    A) 1956.
    B) 1962.
    C) 1964.
    D) 1969.

    HISTORY OF THE DISEASE

    Despite significant accomplishments, it was not until 1958, with more than a century elapsing since the initial discovery of this disease, that the first chemotherapy treatment for MM, melphalan, became available. Measures of success were reported four years later, in 1962, with melphalan being recognized as first-line treatment for the disease.

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    3 . Multiple myeloma is defined as a malignancy of
    A) stromal cells within the iliac crest.
    B) human leukocyte antigen on T-cells.
    C) terminally differentiated B-lymphocytes.
    D) T cells in their role as memory lymphocytes.

    PATHOPHYSIOLOGY

    There is often confusion regarding the classification of MM as a malignancy. Although there is extensive bone destruction throughout the skeletal system created by malignant plasma cells, MM is not considered a bone cancer. It is considered a hematologic malignancy, with some similarities to leukemia in the areas of treatment and subsequent complications of impaired immunity. While leukemic cells circulate in the blood, the malignant plasma cells associated with MM remain within the bone marrow compartment. It has been proposed that these plasma cells can only survive in bone marrow [16].

    Multiple myeloma is defined as a malignancy of plasma cells, specifically terminally differentiated B-lymphocytes. When plasma cells mutate or become aberrant, the Igs produced by plasma cells are homogenous or monoclonal. The myeloma cells produce and secrete the characteristic monoclonal protein (M protein) detected in serum or urine. Various terms denote this paraprotein: protein spike, M spike that has been likened to a church spire, myeloma protein, and "sticky-m" protein. Identification of the M spike is detected by electrophoresis, a laboratory test that separates and identifies proteins [17]. When more light chains are produced than match the heavy chains, light chains are excreted by the kidneys and detected in the urine. This is termed Bence Jones proteinuria.

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    4 . A multiple myeloma patient with anemia, lytic lesions, renal insufficiency, and hypercalcemia, with the absence of light chains in the urine and serum, may be diagnosed with
    A) plasmacytoma.
    B) nonsecretory multiple myeloma.
    C) smoldering, indolent, or asymptomatic multiple myeloma.
    D) monoclonal gammopathy of undetermined significance (MGUS).

    MULTIPLE MYELOMA DIFFERENTIATION

    Nonsecretory MM is a malignant form of the disease characterized by an absence of M protein secreted in either serum or urine (light chains). In patients with nonsecretory MM, plasma cells have become so de-differentiated that they are incapable of producing protein; hence, none are released into blood or urine. These patients present with anemia, lytic lesions, renal impairment, and hypercalcemia [1,22,23].

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    5 . The symptoms that require treatment in patients with indolent or smoldering multiple myeloma that becomes symptomatic are
    A) anemia and lytic lesions.
    B) anemia and renal failure.
    C) anemia and hypocalcemia.
    D) anemia and hypercalcemia.

    MULTIPLE MYELOMA DIFFERENTIATION

    Treatment may not be required for many years. If symptoms develop, erythropoietin may be administered for anemia and bisphosphonates may be prescribed for hypercalcemia. It is imperative that patients follow up with an oncologist on a regular basis to monitor for any disease progression [1,22,23].

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    6 . Multiple myeloma is
    A) diagnosed in 10,710 patients annually.
    B) the cause of an estimated 19,900 deaths.
    C) more frequently diagnosed in women than in men.
    D) the second most common hematologic malignancy.

    EPIDEMIOLOGY/ETIOLOGY OF MULTIPLE MYELOMA

    Multiple myeloma is the second most common hematologic malignancy, and 1.83% of all cancers diagnosed in the United States are myeloma [25]. In 2021, an estimated 34,920 individuals will be diagnosed with MM and an estimated 12,410 individuals will die as a result of the disease [25]. The median age at diagnosis is 69 years. There is evidence that demographic factors may affect the risk of developing the disease. MM occurs twice as frequently in blacks as whites and at a higher ratio in men than in women [25,26]. The 5-year survival rate after diagnosis is approximately 53.9%, with a range of less than six months to more than 10 years [26].

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    7 . Clinical signs and symptoms of multiple myeloma are
    A) lytic lesions, back pain, and hypocalcemia.
    B) back pain, renal impairment, and hypercalcemia.
    C) upper respiratory infection, urinary tract infection, and hypocalcemia.
    D) hypocalcemia, urinary tract infection, and upper respiratory infection.

    CLINICAL PRESENTATION

    It is not unusual for a diagnosis of MM to be determined during a routine physical examination in patients who have presented to the physician's office with totally unrelated symptoms [28]. Blood work usually initially reveals anemia or renal insufficiency, warranting further investigation. In the majority of patients, MM manifests itself between the fifth and seventh decades of life. Many patients attribute their symptoms of lower back or rib pain, fatigue, weakness, and feeling out of breath on exertion to the normal aging process. Patients report their back pain is not relieved at night when resting and increases with a change in position. Neurologic involvement, with paresthesias and sensory loss in the extremities, may also be a presenting symptom [21,24,29]. Patients may voice some frustration during the prediagnosis period, reporting frequent office visits for upper respiratory or recurrent urinary tract infections that never completely resolve.

    Upon initial diagnosis, approximately 80% of the patients have pathologic disease with punched out areas of bone due to lytic lesions; some will have evidence of fractures [28]. Seventy percent of patients presenting with this disease have anemia, and approximately 20% will have an elevated serum creatinine, showing signs of acute or chronic renal impairment [30]. Obviously, a more advanced stage of disease will reveal increased organ involvement or damage, evidenced by hypercalcemia and lytic bone lesions. For patients presenting with a more aggressive disease, this poses a serious problem requiring prompt intervention to halt the disease process [1,2,21]. The hallmarks of the disease—calcium elevation, renal insufficiency, anemia, and bone disease—are known by the acronym CRAB [31].

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    8 . Immunoglobulin (Ig)-mediated immunity protects against invading pathogens. Which Ig prevents antigens from attaching to epithelial cell surfaces?
    A) IgA
    B) IgD
    C) IgE
    D) IgM

    AN OVERVIEW OF MULTIPLE MYELOMA-RELATED PHYSIOLOGY

    IgA is the second most common Ig and is formed as a dimer, a more complicated structure. In general, IgA is found in the mucous membranes in the mouth, saliva, tears, nose, digestive tract, and lungs. It provides defense against micro-organisms by preventing antigens from attaching to epithelial cell surfaces [32,33].

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    9 . The three phases of bone homeostasis are
    A) resorption, reversal, and formation.
    B) formation, reversal, and destruction.
    C) reversal, maintenance, and destruction.
    D) resorption, destruction, and reconstruction.

    AN OVERVIEW OF MULTIPLE MYELOMA-RELATED PHYSIOLOGY

    Bone homeostasis under the normal physiologic process is achieved when there is a balance between bone resorption and bone formation. The cells responsible for remodeling (i.e., osteoblasts, osteocytes, and osteoclasts) participate in three phases of bone homeostasis:

    • Resorption

    • Reversal

    • Formation

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    10 . The major component responsible for new bone formation is
    A) osteocytes.
    B) osteoclasts.
    C) osteoblasts.
    D) bone marrow.

    AN OVERVIEW OF MULTIPLE MYELOMA-RELATED PHYSIOLOGY

    The third and final phase of the growth of new bone occurs during formation. Osteoblasts, the major component of formation, arise from pluripotent stem cells, which differentiate into fibrous tissue, adipocytes, cartilage, or muscle. The periosteum and marrow stromal cells have osteoblast progenitor cells; these cells are committed to differentiate into osteoblasts and are instrumental in acting as receptors for bone growth factors and remodeling. In a slow process over time, the bone matrix fibers introduced by the osteoblasts strengthen and completely fill in the area cleared away by osteoclasts. Flattened lining cells then cover this new area, and a resting phase ensues until the cycle repeats itself.

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    11 . Which of the following is NOT a diagnostic test that is part of the initial work-up for multiple myeloma?
    A) Skeletal survey
    B) Blood glucose level
    C) Complete metabolic panel
    D) Serum protein electrophoresis

    DIAGNOSIS

    Approximately two to three days are required to complete and receive the results from all of the following diagnostic tests when diagnosing MM. Initial diagnostic tests include [21,37,44,47,48]:

    • Complete history and physical

    • Complete blood count (CBC) with manual differentiation and peripheral smear (looking for rouleaux formation)

    • Complete metabolic panel (CMP), which includes blood urea nitrogen (BUN), creatinine, calcium, albumin, and lactate dehydrogenase (LDH)

    • Serum protein electrophoresis (SPEP)

    • Quantitative Ig

    • Urine for urinalysis, culture, and sensitivity

    • Urine protein electrophoresis (UPEP) with immunofixation

    • 24-hour urine collection (looking specifically for Bence Jones light chains)

    • Free light chains in serum

    • Immunofixation electrophoresis (IFE)

    • Skeletal survey (whole body)

    • Whole body magnetic resonance imaging (MRI)

    • Whole body computed tomography (CT) scan

    • 18Fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/CT scan

    • Bone marrow biopsy with aspiration

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    12 . The preferred site for bone marrow aspiration for biopsy in patients with multiple myeloma is the
    A) pelvic bone.
    B) anterior iliac crest.
    C) posterior iliac crest.
    D) nondominant fibula.

    DIAGNOSIS

    Red marrow is the target for biopsy. Realizing that the marrow will have decreased by approximately 50% in adults, with the remainder being adipose tissue, there is little to be gained from sampling marrow from various sites for comparison [22,56]. The iliac crest is usually selected for the aspiration and biopsy and is reportedly the least uncomfortable from all the sites [22,56]. The posterior iliac crest is the preferred site; the anterior iliac crest is an alternative if the patient is unable to lie prone or is obese [22,56]. In patients with MM, the sternum is never the optimum site for the bone marrow aspiration because the bones are too fragile and the procedure would present a heightened risk of perforating the sternum and damaging the underlying organs.

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    13 . According to the Revised International Staging System, a patient with multiple myeloma and a serum ß-2 microglobulin level of less than 3.5 mg/L and a serum albumin of 4 g/dL would be categorized as
    A) stage I.
    B) stage II.
    C) stage III.
    D) None of the above

    STAGING

    REVISED INTERNATIONAL STAGING SYSTEM FOR MULTIPLE MYELOMA

    StageSerum AlbuminSerum ß-2 MicroglobulinSerum Lactate DehydrogenaseChromosomal Abnormalities
    I≥3.5 g/dL<3.5 mg/LNormalStandard risk
    IIAny other combinations of prognostic factors
    IIINA>5.5 mg/LHighHigh risk
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    14 . The average survival time for a patient diagnosed with stage III multiple myeloma is
    A) 12 months.
    B) 29 months.
    C) 44 months.
    D) 62 months.

    STAGING

    Stage I disease has historically been associated with an average survival time of 62 months; stage II survival is an estimated 44 months, and stage III is 29 months [62]. However, overall survival times have increased with newer chemotherapy agents and treatment algorithms. The estimated survival times indicated by disease stage are often very disturbing to patients and families. MM has many variables within the disease process. The disease itself produces complications, compounded with the side effects from specific treatments. It is important to point out that survival is not predetermined and that individuals have lived with the disease for up to 10 years. Patients require support to understand that, with ongoing research, evolving treatments provide new hope and longer survival times [1].

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    15 . For high-risk nontransplant patients with multiple myeloma, treatment often includes
    A) bleomycin.
    B) carfilzomib.
    C) prednisone.
    D) dexamethasone.

    TREATMENT MODALITIES

    Oncology nurses working with inpatients on a medical/oncology unit may never receive orders to administer high-dose chemotherapy to patients with MM, but having knowledge of what this entails is applicable to patient care. Many of the regimens described for transplant candidates are also options for nontransplant candidates. For example, as in transplant-eligible patients, three-drug regimens are preferred by the National Comprehensive Cancer Network (NCCN). Patients ineligible for initiation of treatment with a three-drug regimen can be started with a two-drug regimen, with a third drug added after performance status improves. A two-drug regimen is preferred for elderly and/or frail patients [51]. The preferred regimens for primary therapy of nontransplant patients include [51,69]:

    • Bortezomib/lenalidomide/dexamethasone

    • Daratumumab/lenalidomide/dexamethasone

    • Lenalidomide/low-dose dexamethasone (for frail, elderly patients)

    • Bortezomib/cyclophosphamide/dexamethasone (for patients with acute renal insufficiency)

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    16 . When used as the main form of chemotherapy in nontransplant patients, the standard melphalan regimen is repeated every
    A) 21 days.
    B) 30 days.
    C) 42 days.
    D) 58 days.

    TREATMENT MODALITIES

    As with transplant patients, nontransplant patients are stratified by risk. Although melphalan-containing regimens are no longer considered the standard of care for nontransplant patients, they may be useful in certain circumstances [51]. For example, for nontransplant patients who are not high risk, oral melphalan and prednisone offer an easier mode of administration, with fewer side effects [51,73]. This regimen, which is repeated every 42 days, consists of [69]:

    • Melphalan 9 mg/m2 oral dose given on days 1–4

    • Prednisone 60 mg/m2 given on days 1–4

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    17 . One of the two bisphosphonates approved for use in the treatment of multiple myeloma is
    A) tiludronate.
    B) risedronate.
    C) alendronate.
    D) zoledronic acid.

    TREATMENT MODALITIES

    There are two bisphosphonates currently approved by the U.S. Food and Drug Administration (FDA) for use in the treatment of MM: zoledronic acid and pamidronate. Zoledronic acid is administered once every three to four weeks at a dose of 4 mg over 15 minutes as IV infusion [69]. Zoledronic acid is more costly than pamidronate but is 100 times more potent. Renal function should be monitored for elevated creatinine and albumin levels. In patients who develop renal deterioration with no other apparent cause, bisphosphonate therapy with zoledronic acid or pamidronate should be withheld until the serum creatinine returns to within 10% of the baseline level. Intermittent evaluation (every three to six months) for the presence of albuminuria is recommended. Patients with pre-existing mild-to-moderate renal impairment should receive a reduced dosage of zoledronic acid. Use in patients with severe renal impairment is not recommended. Alternately, a pamidronate dose of 90 mg is administered over four to six hours by IV infusion once every three to four weeks. Pamidronate is used more frequently in patients with MM than zoledronic acid [69,76,80].

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    18 . Medication-related osteonecrosis of the jaw (MRONJ) is more likely to occur
    A) in therapy of shorter duration.
    B) when the medication is halted.
    C) in the maxilla than the mandible.
    D) with the use of more potent bisphosphonate therapy.

    TREATMENT MODALITIES

    Side effects that may arise during the use of bisphosphonates include [23,61,83]:

    • Bone pain

    • Fever

    • GI symptoms: nausea, vomiting, diarrhea (usually transient and do not require treatment)

    • Medication-related osteonecrosis of the jaw (MRONJ): temporary or permanent loss of blood supply to the jaw bone (usually the mandible) resulting in necrotic areas

    MRONJ is a serious and more significant issue. It is characterized by loose teeth and areas of exposed jaw bone, with resulting pain and infection. This condition is more likely to occur with more potent bisphosphonate therapy (e.g., IV zoledronic acid) and with longer duration of therapy [76,84].

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    19 . Due to the risk for severe fetal deformities, women of childbearing age who are prescribed thalidomide must
    A) use one form of birth control.
    B) agree to undergo hysterectomy.
    C) have two negative pregnancy tests prior to beginning thalidomide and will need to be tested for pregnancy at certain times during her treatment (as directed by her physician).
    D) None of the above

    TREATMENT MODALITIES

    Women who take thalidomide must use two acceptable forms of birth control (as directed by their physician) for four weeks before beginning thalidomide, during their treatment, and for four weeks after treatment. The woman must have two negative pregnancy tests prior to beginning thalidomide and will need to be tested for pregnancy in a lab at certain times during her treatment [92]. Women who are two years postmenopausal or have undergone a hysterectomy may be excused from meeting these requirements [92]. Men receiving thalidomide treatment who are sexually active should be counseled to use a condom during treatment or completely avoid any sexual contact with a woman who is pregnant or may become pregnant while taking this medication and for four weeks after completing treatment. Women taking thalidomide cannot breastfeed, and men cannot donate sperm; neither is permitted to donate blood [51,88,92,93,94].

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    20 . Thalidomide produces several actions to combat the effect of malignant myeloma cells, including
    A) promoting fibroblast growth factor.
    B) decreasing the effect of glycoproteins.
    C) potentiating cytokine production and pathways.
    D) inhibiting tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6).

    TREATMENT MODALITIES

    Thalidomide produces several actions to combat the effects of myeloma cells [85,86,90]:

    • Inhibits angiogenesis by blocking fibroblast growth factor

    • Blocks VEGF

    • Inhibits plasma cells and marrow cells

    • Interrupts cytokine production and pathways

    • Down regulates or inhibits TNF-α and IL-6

    • Increases effect of glycoproteins, which have antitumor necrosis factor activity

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    21 . Possible side effects of lenalidomide, an immunomodulator used in the treatment of multiple myeloma, include
    A) anemia.
    B) neutropenia.
    C) thrombocytopenia.
    D) All of the above

    TREATMENT MODALITIES

    The major side effects with lenalidomide, all of which require dose reduction or interruption, are the myelosuppressive effects of neutropenia, anemia, and thrombocytopenia. For patients with a combination regimen including doxorubicin and erythropoietin, the heightened risk of thromboembolic events bears very close monitoring. The GI symptoms of constipation, loss of appetite, and diarrhea are usually less significant than the myelosuppressive effects [9,69,83]. Side effects may be treated as follows [10,83]:

    • Neutropenia: Growth factors

    • Anemia: Transfusion support with packed red blood cells and growth factors

    • Thrombocytopenia: Platelet transfusion

    • GI symptoms: Laxatives, appetite stimulants, antidiarrheals

    • Muscle cramps: Quinine taken at bedtime may relieve leg cramps

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    22 . Which of the following medication regimens is approved for the treatment of multiple myeloma?
    A) Bortezomib, melphalan, and prednisone
    B) Lenalidomide, bortezomib, and dexamethasone
    C) Bortezomib, melphalan, prednisone, and thalidomide
    D) All of the above

    TREATMENT MODALITIES

    Bortezomib is a proteasome inhibitor and one of the more recently developed targeted therapies available for relapsed or refractory MM. Due to the improved survival seen with this drug, it was approved by the FDA as a first-line/induction treatment in 2008. Bortezomib is approved for use alone or in combination with melphalan and prednisone (VMP) [69]. Other combinations used, though not specifically approved for use in the United States, include lenalidomide/bortezomib/dexamethasone (RVD) and bortezomib/melphalan/prednisone/thalidomide (VMPT) [6].

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    23 . Peripheral neuropathy that develops as a result of bortezomib use is generally treated with
    A) gabapentin.
    B) amitriptyline.
    C) acetaminophen.
    D) dexamethasone.

    TREATMENT MODALITIES

    It should be noted that approximately 15% of patients experience severe (grade 3 or 4) neuropathy with the VMP combination [69]. Supplements such as the amino acids L-carnitine and L-glutamine and vitamins B6 and B12 may offer some neuroprotection. Additionally, an mRNA test is in development that would identify patients with MM at risk for bortezomib-induced peripheral neuropathy. The incidence of neuropathy has been demonstrated to be significantly less with subcutaneous bortezomib than with IV administration [6]. Neuropathy can be reversed in the majority of patients with gabapentin.

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    24 . An autologous stem cell transplant uses stem cells obtained from
    A) the patient.
    B) an unrelated donor.
    C) the patient's identical twin.
    D) a cancer-free family member with closely matched HLA type.

    STEM CELL TRANSPLANTATION

    Several types of PBSC transplants are available. The more common and much preferred method for patients with MM is the autologous transplant. This method is usually recommended for eligible patients younger than 70 years of age with newly diagnosed MM, but, as stated, select older patients may be eligible [68]. With autologous transplants, the patient's own cells are harvested and reinfused at the optimum time in an attempt to achieve as complete a remission as possible. Sufficient cells are obtained to allow for tandem transplants if deemed necessary. Tandem transplantation is an option for patients whose response to the first autologous transplant is less than complete. However, the added benefit of tandem transplantation versus a single autologous transplant is unclear [6,110]. Patients given the option of an autologous transplant may choose to go through the induction process and harvest their own stem cells but continue on with maintenance therapy. Their decision, obviously after an in-depth discussion with the3 oncologist, is to wait until they reach a plateau, when they no longer respond to the chemotherapy or immunomodulator, and then undergo the necessary transplant [1,2,23,75,111]. Repeat autologous transplantation (following a single autologous transplant) is an option for patients who relapse after a remission of greater than two years [6].

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    25 . The first phase of the stem cell transplant procedure, induction, has the goal of
    A) increasing the number of stem cells.
    B) obtaining donor stem cells for transplantation.
    C) reducing the number of plasma cells and M protein levels.
    D) monitoring absolute neutrophil count to ensure that engraftment has occurred.

    STEM CELL TRANSPLANTATION

    With preliminary testing completed, the first phase of the transplant procedure is induction, with the goal of reducing the number of plasma cells and M protein levels. Depending on the stage of the disease and taking into account any prior treatments administered, the following chemotherapy, immunomodulators, and/or glucocorticoids may be ordered [21]:

    • Glucocorticoids (e.g., dexamethasone and prednisone)

    • Immunomodulators

      • Thalidomide

      • Lenalidomide

      • Pomalidomide

    • Proteasome inhibitors

      • Bortezomib

      • Carfilzomib

      • Ixazomib

    • Alkylating agents (e.g., melphalan, cyclophosphamide)

    • Other cytotoxic drugs (e.g., vincristine, doxorubicin, and liposomal doxorubicin)

    • Monoclonal antibodies

      • Daratumumab

      • Elotuzumab

    • Histone-deacetylase inhibitors

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    26 . What percentage of bone marrow cells are stem cells?
    A) 1%
    B) 5%
    C) 15%
    D) 40%

    STEM CELL TRANSPLANTATION

    Only 1% of marrow cells are stem cells, and an even smaller percentage exist in the peripheral blood. Stem cells require mobilization to enable sufficient cells for collection. Colony growth stimulating factors is prescribed and given on a daily basis, boosting the number of WBCs and mobilizing them by approximately 18-fold [123]. Patients or care providers will be instructed regarding administration of the subcutaneous injection. Alternatively, patients may receive the injections at an outpatient clinic or infusion center. Most patients and caregivers, however, are able to inject the medication.

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    27 . A patient who exhibits a 90% or greater reduction in M protein levels after stem cell transplant is categorized as having a
    A) good response.
    B) partial response.
    C) complete response.
    D) very good partial response.

    STEM CELL TRANSPLANTATION

    Response to therapy is categorized as [51,87,109,127]:

    • Complete response (CR): No M spike in serum or urine; no detectable soft tissue plasmacytomas; marrow contains 5% or less of plasma cells

    • Very good partial response (VGPR): 90% or greater reduction in M protein

    • Partial response (PR): 50% to 90% reduction in M protein

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    28 . The most common oncologic emergency, occurring in 10% of patients with multiple myeloma, is
    A) renal failure.
    B) hypercalcemia.
    C) atrial fibrillation.
    D) spinal cord compression.

    COMPLICATIONS ASSOCIATED WITH MULTIPLE MYELOMA

    The most common oncologic emergency, hypercalcemia, occurs in greater than 10% of patients with MM [4,6,128]. Calcium maintains teeth and bones and is an essential factor for clotting and intracellular metabolism. Calcium exists in three forms: 45% is bound to protein, 45% is freely ionized, and the remaining 10% is associated with phosphate, sulfate, or citrate [1,4]. Patients with MM are at risk for hypercalcemia due to pathologic bone destruction and the subsequent release of calcium into the circulation. This is an added assault to the kidneys, which may already be impaired; the kidneys can compensate for only a limited time in trying to excrete extra calcium. The normal range of serum calcium is 9–11 mg/dL.

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    29 . The first sign of spinal cord compression is usually
    A) pain.
    B) sensory loss.
    C) autonomic loss.
    D) motor weakness.

    COMPLICATIONS ASSOCIATED WITH MULTIPLE MYELOMA

    As many as 70% of patients diagnosed with MM present with back pain due to lytic lesions of the spine upon initial diagnosis, and lytic lesions in bone never repair. Despite standardized treatment with bisphosphonates and encouraging patients to remain as mobile as possible, vertebral bodies fracture and SCC follows. The early onset of SCC may initially go undetected, but the usual pathologic sequence of this disease is [20,29,61,131,132,133]:

    1. Pain

    2. Motor weakness: Stiffness, heaviness in limbs

    3. Motor loss: Lack of coordination and ataxic gait; paralysis with the continuation of motor loss

    4. Sensory loss: Numbness, paresthesia, inability to sense temperature variations, loss of sensation of deep pressure, inability to sense vibration

    5. Autonomic loss: Early signs of bowel and bladder dysfunction, impotence, loss of sphincter tone (a later sign, equates with poorer prognosis)

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    30 . The initial treatment approach for renal failure in patients with multiple myeloma is
    A) allopurinol.
    B) plasmapheresis.
    C) treatment of the underlying malignancy.
    D) angiotensin-converting enzyme inhibitors.

    COMPLICATIONS ASSOCIATED WITH MULTIPLE MYELOMA

    The initial treatment approach for renal failure in patients with MM is treatment of the underlying malignancy. VAD is effective when rapid reduction in the M protein is a priority. Cyclophosphamide or melphalan and prednisone at a reduced dose may be the preferred choice for older patients. The efficacy of bortezomib in relapsed and refractory MM has been discussed. Studies have also shown that bortezomib-based regimens may be effective in patients with MM who present with renal failure [146,147,148,149,150]. If angiotensin-converting enzyme (ACE) inhibitors and diuretics are being taken, they should be discontinued immediately. Diet modification is often also necessary.

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