June 2004, Volume 8, Number 3

Clinical Q&A

Barbara Holmes Gobel, RN, MS, AOCN^®, Associate Editor

Management of Acneiform Rashes Related to Gefitinib Therapy

Michelle Purdom, RN, BSN

Question: What is the best strategy for the management of acneiform rashes resulting from gefitinib (Iressa^®, AstraZeneca, Wilmington, DE) therapy?

Answer: In May 2003, gefitinib, an oral cancer agent, was granted accelerated approval by the U.S. Food and Drug Administration as monotherapy for patients with locally advanced or metastatic non-small cell lung cancer whose disease had failed to respond to platinum-based and docetaxel chemotherapies. Gefitinib also is under investigation in many research studies for the treatment of various epithelial cancers such as breast, colon, head and neck, brain, and gynecologic.

This is an exciting and challenging time for nurses as they are presented with new and innovative treatments for patients with cancer. Nurses also are faced with new side-effect profiles. Few published studies about the etiology of the toxicities with epidermal growth factor receptor (EGFR) inhibitors such as gefitinib are available, but the exact mechanism for these toxicities still is not known. Only a few published recommendations are available on how to treat these toxicities, and these are based on individual practitioners' experience (Herbst, LoRusso, Purdom, & Ward, 1998; Herbst, Maddox, & Rothenberg, 2002; Riddle, Lee, & Purdom, 2002). Nurses are left to draw on these reports and their experience to determine the best treatment for these side effects.

Gefitinib belongs to a class of drugs called EGFR-tyrosine kinase inhibitors. Gefitinib blocks EGFR, which prevents activation of tyrosine kinase and switches off signals from EGFR. Tyrosine kinase transmits cell-to-cell signals concerning growth, differentiation, adhesion, motility, and death. The human EGFR family is overexpressed or dysfunctional in many human malignancies, including lung cancer. These receptors are targets for cancer therapy, hence the term "targeted therapies." Gefitinib works differently from chemotherapy drugs. Gefitinib is a targeted therapy; the side effects are less toxic than those of conventional chemotherapy drugs, but they are unique.

Gefitinib received approval based on the phase II Iressa Dose Evaluation in Advanced Lung Cancer 2 Trial in patients with advanced non-small cell lung cancer whose disease failed to respond to platinum- and docetaxel-based regimens. The study treated 216 patients. Patients in one arm of the study (n = 102) received 250 mg per day, and patients in the other arm of the study (n = 114) received 500 mg per day. Patients' tumor responses and duration of responses were clinically significant. Tumor response rates for the 250 mg and 500 mg per day groups were 11.8% (95% confidence interval, 6.2%-19.7%) and 8.8% (95% confidence interval, 4.3%-15.5%), respectively, with tumor response duration ranging from three to seven or more months. Stable disease was seen in 31% and 27% of the 250 mg and 500 mg per day arms, respectively (Kris, Natale, & Herbst, 2002). Favorable symptom responses were seen in 78% of patients, with approximately 60% of the patients reporting improvement by the second week of treatment (Kris et al.). Symptom response was measured by means of the Functional Assessment of Cancer Therapy lung and lung cancer subscales. These patient questionnaires are designed to measure the patients' own assessment of their quality of life. The dose-limiting toxicities of gefitinib, diarrhea and skin rash, were determined in early phase I trials. These same toxicities were seen once again in the phase II trials. Most drug-related adverse events were mild, including reversible grade 1 or 2 diarrhea and skin rash. Approximately 0.33% of patients taking gefitinib died from interstitial lung disease, a lung condition that the manufacturer has reported as a possible side effect of this treatment (AstraZeneca Pharmaceuticals, 2003).

The cutaneous adverse effects of gefitinib are similar to those of other EGFR-targeted agents. The most common toxicities result from direct interference with the functions of EGFR's signaling in the skin and include skin manifestations such as rash (macular, papular, or pustular), dry skin, and pruritus. (See Figure 1 and Figure 2 for a view of a patient experiencing rashes related to gefitinib administration.) Also commonly reported as an adverse side effect of gefitinib is diarrhea, which generally is well tolerated and treatable with over-the-counter antidiarrheals. All of these side effects are reversible upon discontinuation of the drug. Patients must realize that they are not having an allergic reaction to the drug, and they should seek treatment for side effects as soon as they occur.

In the author's experience treating patients receiving gefitinib, clindamycin T gel (Cleocin T^® gel, Pfizer Inc., New York, NY) in combination with washing with soap and water and using an unscented moisturizing cream for the management of individual pustules has worked very well. For widespread pustules, clindamycin lotion may be easier to apply. Patients should be cautioned that clindamycin T gel may work only on the pustules and is not appropriate for a macular rash. Overuse of clindamycin T gel may cause the skin to become too dry. If that happens, patients should stop the gel and use a nonperfumed moisturizer, and the physician may consider use of an oral antibiotic. Oral antibiotic treatment such as minocycline hydrochloride (Minocin^®, Wyeth, Madison, NJ) or sulfamethoxazole-trimethoprim (Bactrim DS^®, Roche Pharmaceuticals, Nutley, NJ) also may be considered when the rash is widespread (i.e., more than 50% of the body surface area) or bothersome. Very few bacteria have been found in skin biopsies of pustules, but antibiotics have been reported to be beneficial as treatment. At the University of Texas M.D. Anderson Cancer Center in Houston, treatment with gefitinib normally is withheld if the rash progresses to include more than 50% of the body surface area with symptomatic erythroderma or if macular, papular, or vesicular eruption or desquamation occurs. M.D. Anderson Cancer Center also has found that treatment with topical hydrocortisone does not provide consistent clinical benefit but may be considered for treatment of a widespread rash. Another consideration for a rash that is widespread and intolerable would be a dose reduction or alternate dosing (e.g., two weeks taking the drug and a one-week break from the drug). Patients with a history of acne, rosacea, or other skin disorders may benefit from closer observation by a dermatologist. A dermatologic consult prior to starting treatment and consults as needed while taking gefitinib may help in managing the rash. The expertise of a dermatologic consult may provide some ideas for management of the rash that were not considered by the primary practitioner.

AstraZeneca has created educational handouts for patients taking gefitinib. However, AstraZeneca provides no stated recommendations for the treatment of skin toxicities. In the author's experience with this therapy, patients generally have been tolerant of the acneiform rashes. The rash tends to wax and wane during the course of treatment. The best treatment for the rash often is found through trial and error because patients differ in how easily their rashes are controlled.

References

AstraZeneca Pharmaceuticals. (2003). Iressa^® [Package insert]. Wilmington, DE: Author.

Herbst, R.S., LoRusso, P.M., Purdom, M., & Ward, D. (1998). Dermatologic side effects associated with gefitinib therapy: Clinical experience and management. Clinical Lung Cancer, 4, 366-369.

Herbst, R.S., Maddox, A.M., & Rothenberg, M.L. (2002). Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well tolerated and has activity in non-small-cell lung cancer and other solid tumors: Results of a phase I trial. Journal of Clinical Oncology, 15, 3815-3825.

Kris, M., Natale, R.B., & Herbst, R.S. (2002). A phase II trial of ZD1839 ('Iressa') in advanced non-small cell lung cancer patients who had failed platinum- and docetaxel-based regimens (IDEAL 2) [Abstract 1166]. Proceedings of the American Society of Clinical Oncology, 21, 292a.

Riddle, J., Lee, P., & Purdom, M. (2002). The epidermal growth factor receptor as a novel target for cancer therapy: Case studies and clinical implications. Seminars in Oncology Nursing, 18 (Suppl. 4), 11-19.

Michelle Purdom, RN, BSN, is a research nurse supervisor in the Department of Cancer Medicine Phase 1 Unit at the University of Texas M.D. Anderson Cancer Center in Houston. (Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Clinical Journal of Oncology Nursing or the Oncology Nursing Society.)

Author Contact: Michelle Purdom, RN, BSN, can be reached at mpurdom@mdanderson.org, with copy to editor at CJONeditor@jsobel.com.

Key Words: epidermal growth factor receptors, malignancy

Joseph D. Tariman, RN, APN, MN, APRN-BC, OCN^®

Question: Why do some patients with multiple myeloma undergo more frequent magnetic resonance imaging (MRI), and what are the nursing implications of MRI results?

Answer: Traditional radiographic skeletal survey (metastatic bone survey) has been used to assess for the presence of osteolytic lesions to estimate the tumor burden associated with multiple myeloma as defined by the Durie-Salmon staging system (Durie & Salmon, 1975; Sheridan & Serrano, 2001). Increases in the number and size of bony lytic lesions (usually three or more lesions) reflect advanced metastatic disease. Subsequent follow-up radiographic skeletal surveys during and after treatment help to determine worsening of myeloma status, based on the occurrence of new lytic lesions and/or increases in their size. One of the disadvantages of skeletal survey is the lack of sensitivity, particularly in determining response to treatment (Angtuaco, Moulopoulos, Hronas, & Avva, 2002).

MRI of the major skeleton (skull, spine [cervical, thoracic, lumbar], and pelvis) offers many advantages in patients with multiple myeloma (Angtuaco et al., 2002). Advantages include, but are not limited to,

• Defining the extent of disease in the axial skeleton (bones constituting the head and trunk of the vertebral body)
• Defining diffuse myeloma (extensive infiltration of malignant plasma cells in the bone marrow) versus focal myeloma (multiple, small areas of plasma cell infiltration).
• Assessing associated findings such as existing or impending fractures and cord compression.
• Finding areas for possible computerized tomography-guided biopsy.
• Assessing response to therapy.

MRI also has the potential to predict disease progression in patients with stage I multiple myeloma (Dimopoulos, Moulopoulos, Smith, Delasalle, & Alexanian, 1993; Mariette et al., 1999; Van de Berg et al., 1996) and identify patients with multiple myeloma who are at higher risk for vertebral compression fractures (Lecouvet et al., 1997). MRI has been found to have some correlation with laboratory indexes of myeloma; for example, diffuse abnormal marrow patterns correlate with the percentage of plasma cells in the bone marrow (higher percentage of plasma cells means higher tumor burden correlating with diffuse marrow patterns in MRI), and lower hemoglobin levels correlate with advanced myeloma (Kusomoto et al., 1997; Lecouvet et al., 1998; Moulopoulos et al., 1992). And, lastly, MRI can be a useful tool in differentiating among multiple myeloma and monoclonal gammopathies of unknown significance (MGUS) (Bellaiche et al., 1997). MGUS is a benign condition but a known precursor to myeloma (Kyle et al., 2002).

The major disadvantage of this diagnostic procedure is the high cost of MRI. Other parts of the skeleton, such as the ribs, tibia, fibula, femur, and humeri, also could have osteolytic lesions related to multiple myeloma, but scanning the entire skeleton is not cost effective. The National Comprehensive Cancer Network (NCCN) practice guidelines have not included MRI as part of the standard diagnostic tests in patients with multiple myeloma, but the test is considered useful in some instances such as suspected cord compression and suspicion of solitary plasmacytoma of bone (NCCN, 2003). True solitary plasmacytoma is a rare event; therefore, MRI of the entire spine is very useful in detecting occult plasmacytomas that are difficult to assess by conventional radiographic films (Shrieve, 2002).

MRI scanning in patients with multiple myeloma has gained popularity among myeloma experts since the early 1990s because of its advantages. Although MRI is not included in the NCCN practice guidelines as part of the initial diagnostic workup, most myeloma centers widely use MRI as an adjunct diagnostic tool to supplement traditional radiographic skeletal survey, particularly in clarifying response to therapy in patients with equivocal clinical changes or in nonsecretory myeloma (Dimopoulos et al., 2000; Moulopoulos, Dimopoulos, Alexanian, Leeds, & Libshitz, 1994). One percent to 2% of patients with multiple myeloma have neither serum nor urine monoclonal proteins (true nonsecretors type) usually detected by electrophoresis and/or immunofixation test, tests that generally are used to diagnose multiple myeloma. Surveillance of disease progression and the assessment of disease response to treatment in nonsecretor types of myeloma are difficult to determine because of the absence of the M protein, which usually is followed to determine treatment effectiveness. Disease progression in multiple myeloma is defined by a sustained increase of greater than or equal to 25% in the M protein in serum or urine. Disease progression also may be noted by development of new sites of lytic lesions or hypercalcemia. Response to treatment is defined by a sustained decline of greater than or equal to 50% in the M protein in serum or urine without the occurrence of hypercalcemia or development of new sites of lytic lesion (NCCN, 2003). Clearly, MRI offers clinicians an additional tool not only in assessing the extent of the disease but also in determining response to treatment.

Understanding Magnetic Resonance Imaging Interpretations

The appearance in MRI of the bones depends, to a large extent, on the unmineralized content of the bone cavities. MRI offers the opportunity to map the distribution of yellow and red marrow because they contain a large number of fat protons and water protons, respectively (Van de Berg, Malghem, Lecouvet, & Maldague, 1998). Protons are positively charged particles within a molecule that react to negatively charged particles from a magnetic field, such as MRI, creating images for interpretation. Two important MRI factors distinguish a normal and abnormal MRI appearance of the bone marrow.

• Degree of distribution of the bony trabecula, fat, and water (Angtuaco et al., 2002; Ricci et al., 1990; Van de Berg et al.)
  • Age-related distribution (i.e., physiologic conversion from cellular or red marrow to fatty or yellow marrow with advancing age, starting at adolescence)
• Actual technique used for imaging (imaging parameters or types of MRI sequences) (see Table 1)
  • T1-weighted sequence provides good contrast in the presence of abundant fatty marrow between normal bone marrow and plasma cell infiltrated bone marrow.
  • Short tau-inversion recovery (STIR) sequence results in short inversion time using fat-suppression technique (enhancing fatty marrow appearance because detecting plasma cell tumor is difficult when red marrow predominates the bone).
  • Postcontrast T1-weighted sequence (with IV administration of gadolinium-chelate compounds and fat suppression), increased uptake of gadolinium by malignant plasma cells, causes a bright appearance, hence distinguishing focal from diffuse involvement.

All three sequences usually are used for comparison or differential in suspected areas of myeloma involvement of the bone marrow.

Knowledge of age-related distribution patterns of cellular and fatty marrow and the use of correct technique are critical to the interpretation of MRI studies. Before adolescence, the bone marrow is largely hematopoietic (red), and after adolescence, the marrow starts to convert into yellow (fatty) marrow. The axial skeleton (spine, ribs, pelvis, skull, and the proximal metaphyses of the femur and humerus) eventually becomes fatty in the fourth decade of life, and, by the sixth decade, the marrow is composed mainly of fatty marrow (Ricci et al., 1990). In most cases of myeloma, where the median age of diagnosis is 65 and 80% of patients are older than 60 years (Blade, Kyle, & Greipp, 1996), the axial skeleton is expected to be composed mainly of fatty marrow, which makes differentiating normal versus abnormal marrow appearance easier.

At the Northwestern University Medical Faculty Foundation, myeloma protocol MRI (specific MRI parameters are set to look into bone marrow distribution to assess myeloma disease, such as T1, STIR, and T1 postgadolinium images) of axial skeleton (skull, cervical and thoracolumbar spine, and pelvis) usually is obtained to assess myeloma burden. This protocol includes sagittal T1 and axial STIR and coronal T1 postcontrast for the MRI of the skull. For the spine, sagittal STIR and T1-weighted or axial and sagittal T1 with contrast and fat saturation suppression sequences usually are obtained. For the pelvis, T1-weighted pre- and postcontrast and STIR sequences usually are done.

The STIR sequence is a fat-suppression technique that allows better visualization of cellular lesions (the higher the hematopoietic content of the marrow [red marrow], the more difficult it is to detect tumors). Hence, focal and diffuse lesions stand out against the background of a fat-suppressed marrow. This technique is highly reproducible and has good accuracy when a large field of view such as the pelvis is imaged (Angtuaco et al., 2002). T1-weighted and STIR images could alert the nurse about areas of compression fractures or specific sites of lytic lesions. The MRI report usually mentions the areas of involvement. Nursing care plans should focus on the prevention of further injury to the affected sites. Physicians may prescribe the use of a body brace for multiple compression fractures in the thoracolumbar region, cervical collar for cervical compression fractures, wheelchair, and a walker or cane for large pelvic or femoral bone destruction. Nurses must emphasize adherence to the use of these supportive devices. Ongoing pain assessment and management using the World Health Organization (WHO) pain "treatment ladder" also become part of daily nursing care (WHO, 1990). Direct application of analgesic patches to affected sites may be beneficial. Other specific nursing interventions for pain include assessment and documentation of the individual's severity of pain (0-10 scale), proper positioning of affected limbs, use of supports and braces (cervical collar, back brace, sling) to prevent additional stress on bones, and consultation with physical or occupational therapists. An important component of patient teaching is emphasizing the signs and symptoms of spinal cord compression and when to seek immediate medical attention, particularly in patients whose MRI shows epidural extension or encroachment.

In general, overall background marrow signal of MRI of the axial skeleton of patients with multiple myeloma will show hypointense (dim) appearance on a T1-weighted sequence and hyperintense (bright) on STIR sequence, and enhancement will be seen on T1-weighted postcontrast with fat suppression (see Figure 1). If the MRI is normal, the T1-weighted images appear hyperintense (bright), STIR images appear hypointense (dim), and no enhancement will be seen in T1-weighted postcontrast with fat suppression (Angtuaco et al., 2002).

Other changes in the bones and marrow affect the MRI in patients with myeloma (Angtuaco et al., 2002), including

• Parallel zones of hypointensity along the vertebral margins on T1-weighted images caused by early osteopenic fractures. Edema related to recent compression fractures also may simulate myeloma lesions.
• Irradiated marrow areas, particularly in the spine, are seen as distinct zones of hyperintensity on T1-weighted sequences instead of the usual hypointense appearance and zone of hypointense signal on STIR images instead of hyperintense signal. This is because of the killing effect of radiation to the cellular elements of the marrow that mostly transforms the irradiated area to a primarily fatty marrow (see Figure 2).
• Severe anemia (which stimulates hematopoietic activity in the bone marrow), diffuse marrow fibrosis, and diffuse blastic metastases to the bone marrow cause the marrow signal to be hypointense on T1 and STIR images (instead of the normal hyperintense signal in T1-weighted sequences) because they can simulate appearance of myeloma lesions.

Nursing Implications

MRI offers many advantages compared to a traditional radiographic skeletal survey. Adequate knowledge and understanding of MRI results can be used to plan nursing care for patients with multiple myeloma. Interpretations from MRI, such as impending cord compression, early osteopenic fractures, pathologic compression fractures, extent of the disease, and response to treatment, are important clinical data that should be addressed appropriately. Specific nursing assessments can provide early recognition of spinal cord compression (Sheridan, 1996). Oncology nurses play a vital role in assisting patients to cope with multiple myeloma by developing individualized nursing interventions based on MRI results and interpretations. Pain is a common symptom manifested by patients with multiple myeloma, particularly those with bone destruction. For patients with multiple compression fractures of the spine, oncology nurses can facilitate ongoing adequate pain assessment and management, which may have positive effects on their quality of life (Poulos, Gertz, Pankratz, & Post-White, 2001). Education in patients with abnormal MRI findings should include recognition of early signs and symptoms of impending cord compression, pain control measures, safety measures, and prevention of pathologic fractures.

References

Angtuaco, E.J., Moulopoulos, A., Hronas, T., & Avva, R. (2002). Imaging studies. In J. Mehta & S. Singhal (Eds.), Myeloma (pp. 297-309). London: Martin Dunitz.

Bellaiche, L., Laredo, J., Liote, F., Koeger, A.C., Hamze, B., Ziza, J.M., et al. (1997). Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. Spine, 22, 2551-2557.

Blade, J., Kyle, R.A., & Greipp, P.R. (1996). Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years. British Journal of Haematology, 93, 345-351.

Dimopoulos, M.A., Moulopoulos, A., Datseris, I., Weber, D., Delasalle, K., Gika, D., et al. (2000). Imaging of myeloma bone disease--Implications for staging, prognosis, and follow-up. Acta Oncologica, 39, 823-827.

Dimopoulos, M.A., Moulopoulos, A., Smith, T., Delasalle, K.B., & Alexanian, R. (1993). Risk for disease progression in asymptomatic multiple myeloma. American Journal of Medicine, 94, 57-61.

Durie, B.G., & Salmon, S.E. (1975). A clinical staging system for multiple myeloma: Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer, 36, 842-854.

Kusomoto, S., Jinnai, I., Itoh, K., Kawai, N., Sakata, T., Matsuda, A., et al. (1997). Magnetic resonance imaging patterns in patients with multiple myeloma. British Journal of Haematology, 99, 649-655.

Kyle, R.A., Therneau, T.M., Rajkumar, S.V., Offord, J.R., Larson, D.R., Plevak, M.F., et al. (2002). A long-term study of prognosis in monoclonal gammopathy of undetermined significance. New England Journal of Medicine, 346, 564-569.

Lecouvet, F.E., Malghem, J., Michaux, L., Michaux, J.L., Lehmann, F., Maldague, B.E., et al. (1997). Vertebral compression fractures in multiple myeloma. Part II. Assessment of fracture risk with MR imaging of the spinal bone marrow. Radiology, 204, 201-205.

Lecouvet, F.E., Van de Berg, B.C., Michaux, L., Malghem, J., Maldague, B.E., Jamart, J., et al. (1998). Stage III multiple myeloma: Clinical and prognostic value of spinal marrow MR imaging. Radiology, 209, 653-660.

Mariette, X., Zagdanski, A.M., Guermazi, A., Bergot, C., Arnould, A., Frija, J., et al. (1999). Prognostic value of vertebral lesions detected by magnetic resonance imaging in patients with stage I multiple myeloma. British Journal of Haematology, 104, 723-729.

Moulopoulos, L.A., Dimopoulos, M.A., Alexanian, R., Leeds, N.E., & Libshitz, H.I. (1994). Multiple myeloma: MR patterns of response to treatment. Radiology, 193, 441-446.

Moulopoulos, L.A., Varma, D.G., Dimopoulos, M.A., Leeds, N.E., Kim, E.E., Johnston, D.A., et al. (1992). Multiple myeloma: Spinal MR imaging in patients with untreated newly diagnosed disease. Radiology, 185, 833-840.

National Comprehensive Cancer Network. (2003). NCCN 2002 multiple myeloma clinical practice guidelines in oncology. In The complete library of NCCN clinical practice guidelines in oncology [CD-ROM]. Rockledge, PA: Author.

Poulos, A.R., Gertz, M.A., Pankratz, V.S., & Post-White, J. (2001). Pain, mood disturbance, and quality of life in patients with multiple myeloma. Oncology Nursing Forum, 28, 1163-1171.

Ricci, C., Cova, M., Kang, Y.S., Yang, A., Rahmouni, A., Scott, W.W., Jr., et al. (1990). Normal age-related patterns of cellular and fatty bone marrow distribution in the axial skeleton: MR imaging study. Radiology, 177, 83-88.

Sheridan, C.A. (1996). Multiple myeloma. Seminars in Oncology Nursing, 12, 59-69.

Sheridan, C.A., & Serrano, M. (2001). Multiple myeloma. In C.H. Yarbro, M.H. Frogge, M. Goodman, & S.L. Groenwald (Eds.), Cancer nursing: Principles and practice (5th ed., pp. 1354-1370). Sudbury, MA: Jones and Bartlett.

Shrieve, D.C. (2002). The role of radiotherapy. In J. Mehta & S. Singhal (Eds.), Myeloma (pp. 367-381). London: Martin Dunitz.

Van de Berg, B.C., Lecouvet, F.E., Michaux, L., Labaisse, M., Malghem, J., Jamart, J., et al. (1996). Stage I multiple myeloma: Value of MR imaging of the bone marrow in the determination of prognosis. Radiology, 201, 243-246.

Van de Berg, B.C., Malghem, J., Lecouvet, F.E., & Maldague, B.E. (1998). Magnetic resonance imaging of normal bone marrow. European Radiology, 8, 1327-1334.

World Health Organization. (1990). Cancer pain relief and palliative care: Report of a WHO expert panel. Geneva, Switzerland: Author.

Joseph D. Tariman, RN, APN, MN, APRN-BC, OCN^®, is a certified nurse practitioner in the Multiple Myeloma Program in the Department of Medicine in the Division of Hematology/Oncology at the Northwestern University Medical Faculty Foundation in Chicago, IL.

Author Contact: Joseph D. Tariman, RN, APN, MN, APRN-BC, OCN^®, can be reached at jtariman@nmff.org, with copy to editor at CJONeditor@jsobel.com.

Key Words: magnetic resonance imaging, myeloma