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Bildgebung bei „smoldering“ (asymptomatischem) multiplem Myelom

Vergangenheit, Gegenwart und Zukunft

Imaging in smoldering (asymptomatic) multiple myeloma

Past, present and future

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Zusammenfassung

Klinisches Problem

Aktuelle klinische Studien sprechen für eine Therapie des „smoldering multiple myeloma” (SMM) mit hohem Progressionsrisiko schon bei der Diagnosestellung und nicht erst zum Zeitpunkt der Progression in ein symptomatisches multiples Myelom (MM). Die Früherkennung einer Knochen- und/oder Knochenmarkbeteiligung durch entsprechende sensitive Bildgebungsverfahren kann zur Ermittlung von SMM-Patienten mit hohem Risiko für eine Progression beitragen.

Radiologische Standardverfahren

Nach aktuellen Konsensusleitlinien (2011) ist die Röntgenuntersuchung des Skeletts ein Grundpfeiler der Beurteilung einer Knochenbeteiligung bei Diagnosestellung und in Verlaufskontrollen wegen eines SMM. Jedoch hat die Röntgenuntersuchung des Skeletts eine geringe Sensitivität für Knochenläsionen und liefert keine Informationen zu Knochenmarkveränderungen.

Innovative Verfahren

Moderne bildgebende Verfahren wie die Fluordeoxyglukose-Positronenemissionstomographie-Computertomographie (FDG-PET-CT) und die Magnetresonanztomographie (MRT) liefern zusammen mit innovativen Funktionsuntersuchungen eine bessere Einschätzung allgemeiner Veränderungen im Knochenmark- und im Knochenkompartiment. Mit diesen Verfahren kann die beginnende Progression vom SMM zum MM quantitativ objektiviert werden.

Leistungsfähigkeit

Obwohl moderne Bildgebungsverfahren häufig zum Staging und zur Risikoabschätzung bei multiplem Myelom eingesetzt werden, sind sie nur in begrenztem Maß bei SMM untersucht worden. Die spärlichen Daten zum SMM zeigen, dass 2 oder mehr in der MRT entdeckte umschriebene Knochenmarkveränderungen Indikatoren für eine rasche Progression in ein symptomatisches Stadium sind. Ob die FDG-PET-CT in asymptomatischen Stadien ähnliche Aussagen erlaubt, ist nach aktueller Datenlage noch unklar.

Ergebnisse

Moderne Bildgebungsverfahren sind der Skelettradiographie in Bezug auf Spezifität und Sensitivität überlegen und sollten dieser bei Hochrisikopatienten mit asymptomatischem Myelom vorgezogen werden. In Zukunft sollte in jedem Fall eine Ganzkörperbildgebung erfolgen, die Läsionen des Knochenmarks und des mineralisierten Knochens sensitiv nachweist und mit so wenig ionisierender Strahlung und Kontrastmittel wie möglich auskommt.

Praktische Empfehlungen

Neuere Bildgebungsverfahren müssen in prospektiven klinischen Studien zur Untersuchung des Übergangs vom SMM zum MM validiert werden; Ziel sollte dabei sein, angemessene Therapieentscheidungen zu ermöglichen. Außerdem sind Bemühungen zur Kostensenkung und größeren Verfügbarkeit von Ganzkörper-MRT und/oder FD-PET-CT erforderlich, um deren flächendeckende Einführung als zuerst eingesetzte diagnostische Verfahren zu erleichtern. Für zukünftige klinische Studien zur Therapie früher Stadien sind systematische Fehler wie „lead-time bias“ und „length-time bias“ zu berücksichtigen, die einen Nutzen einer sensitiven Diagnostik und einer frühen Therapie vortäuschen können.

Die englische Volltextversion dieses Beitrags ist über SpringerLink (unter „Supplemental“) verfügbar.

Abstract

Clinical issue

Emerging clinical trial data support treatment of high-risk smoldering multiple myeloma (SMM) upon diagnosis, and not only at the time of progression to symptomatic complications (multiple myeloma). Early detection of bone and/or bone marrow involvement by sensitive imaging modalities may help define SMM patients at a high risk of progression.

Standard radiological methods

Current (2011) consensus guidelines recognize skeletal survey as a cornerstone modality for assessment of bone involvement at initial diagnosis and during follow-up of SMM. Skeletal survey has severe limitations related to underdetection of bone lesions and also provides no information on bone marrow abnormalities.

Methodical innovations

Modern imaging strategies such as fluorodeoxyglucose positron-emission tomography/CT (FDG PET/CT) and MRI, in conjunction with functional innovations, provide improved estimates of global abnormalities in the bone marrow and bone compartments. These methods have the potential to objectively quantify early transformation from SMM to multiple myeloma.

Performance

Although frequently used for staging and risk prognostication in multiple myeloma, modern imaging techniques have only been evaluated to a limited extent in SMM. Scant data in SMM indicate the prognostic value of two or more MRI-detected focal bone marrow abnormalities, which, if present, predict rapid progression to multiple myeloma. Data evaluating the role of FDG PET/CT in detecting early bone marrow abnormalities as an aid to predicting risk or directing treatment in SMM is currently lacking.

Achievements

The superior specificity and sensitivity of modern imaging techniques compared to skeletal survey suggest that these should have a place in standard practice management of patients at a high risk of SMM progression. The model imaging of the future should be an all-in-one strategy offering high diagnostic performance for bone marrow abnormalities and low-volume bone lesions, as well as allowing monitoring by minimizing radiation exposure and the need for contrast agents.

Practical recommendations

Newer imaging techniques need to be validated in prospective clinical trials assessing the SMM to multiple myeloma transition, with the aim of enabling appropriate management decisions. Efforts are also needed to improve the costs and availability of whole-body MRI and/or FDG PET/CT, in order to facilitate their widespread adoption as first-line detection modalities. Future clinical trials of therapeutic agents using earlier detection strategies will have to be carefully designed and take into consideration the risk of lead-time and length-time biases, which might falsely demonstrate longer overall survival.

The English full text version of this article is available at SpringerLink (under “Supplemental”).

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Literatur

  1. Landgren O, Waxman AJ (2010) Multiple myeloma precursor disease. JAMA 304:2397–2404

    Article  CAS  PubMed  Google Scholar 

  2. Dimopoulos M, Kyle R, Fermand JP et al (2011) Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood 117:4701–4705

    Article  CAS  PubMed  Google Scholar 

  3. Waxman AJ, Kuehl M, Balakumaran A et al (2010) Smoldering (asymptomatic) multiple myeloma: revisiting the clinical dilemma and looking into the future. Clin Lymphoma Myeloma Leuk 10:248–257

    Article  PubMed  Google Scholar 

  4. Perez-Persona E, Vidriales MB, Mateo G et al (2007) New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 110:2586–2592

    Article  CAS  PubMed  Google Scholar 

  5. Dispenzieri A, Kyle RA, Katzmann JA et al (2008) Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 111:785–789

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Gonsalves WI, Rajkumar SV, Gupta V et al (2014) Quantification of clonal circulating plasma cells in newly diagnosed multiple myeloma: implications for redefining high-risk myeloma. Leukemia

  7. Kyle RA, Remstein ED, Therneau TM et al (2007) Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 356:2582–2590

    Article  CAS  PubMed  Google Scholar 

  8. Neben K, Jauch A, Hielscher T et al (2013) Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load. J Clin Oncol 31:4325–4332

    Article  PubMed  Google Scholar 

  9. Rajkumar SV, Gupta V, Fonseca R et al (2013) Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma. Leukemia 27:1738–1744

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Mateos MV, Hernandez MT, Giraldo P et al (2013) Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 369:438–447

    Article  CAS  PubMed  Google Scholar 

  11. Wisloff F, Andersen P, Andersson TR et al (1991) Incidence and follow-up of asymptomatic multiple myeloma. The myeloma project of health region I in Norway. II. Eur J Haematol 47:338–341

    Article  CAS  PubMed  Google Scholar 

  12. D’Arena G, Gobbi PG, Broglia C et al (2011) Pamidronate versus observation in asymptomatic myeloma: final results with long-term follow-up of a randomized study. Leuk Lymphoma 52:771–775

    Article  Google Scholar 

  13. Hillengass J, Bauerle T, Bartl R et al (2011) Diffusion-weighted imaging for non-invasive and quantitative monitoring of bone marrow infiltration in patients with monoclonal plasma cell disease: a comparative study with histology. Br J Haematol 153:721–728

    Article  PubMed  Google Scholar 

  14. Walker R, Barlogie B, Haessler J et al (2007) Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol 25:1121–1128

    Article  PubMed  Google Scholar 

  15. Zamagni E, Patriarca F, Nanni C et al (2011) Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood 118:5989–5995

    Article  CAS  PubMed  Google Scholar 

  16. Dimopoulos M, Terpos E, Comenzo RL et al (2009) International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia 23:1545–1556

    Article  CAS  PubMed  Google Scholar 

  17. Edelstyn GA, Gillespie PJ, Grebbell FS (1967) The radiological demonstration of osseous metastases. Experimental observations. Clin Radiol 18:158–162

    Article  CAS  PubMed  Google Scholar 

  18. Murray I, Kalemis A, Glennon J et al (2010) Time-of-flight PET/CT using low-activity protocols: potential implications for cancer therapy monitoring. Eur J Nucl Med Mol Imaging 37:1643–1653

    Article  PubMed  Google Scholar 

  19. Hara AK, Paden RG, Silva AC et al (2009) Iterative reconstruction technique for reducing body radiation dose at CT: feasibility study. AJR Am J Roentgenol 193:764–771

    Article  PubMed  Google Scholar 

  20. Masuda Y, Kondo C, Matsuo Y et al (2009) Comparison of imaging protocols for 18F-FDG PET/CT in overweight patients: optimizing scan duration versus administered dose. J Nucl Med 50:844–848

    Article  PubMed  Google Scholar 

  21. Baur-Melnyk A, Buhmann S, Becker C et al (2008) Whole-body MRI versus whole-body MDCT for staging of multiple myeloma. AJR Am J Roentgenol 190:1097–1104

    Article  PubMed  Google Scholar 

  22. Gleeson TG, Moriarty J, Shortt CP et al (2009) Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions, and correlation of disease distribution with whole-body MRI (WBMRI). Skeletal Radiol 38:225–236

    Article  CAS  PubMed  Google Scholar 

  23. Bauerle T, Hillengass J, Fechtner K et al (2009) Multiple myeloma and monoclonal gammopathy of undetermined significance: importance of whole-body versus spinal MR imaging. Radiology 252:477–485

    Article  PubMed  Google Scholar 

  24. Ghanem N, Lohrmann C, Engelhardt M et al (2006) Whole-body MRI in the detection of bone marrow infiltration in patients with plasma cell neoplasms in comparison to the radiological skeletal survey. Eur Radiol 16:1005–1014

    Article  PubMed  Google Scholar 

  25. Horger M, Weisel K, Horger W et al (2011) Whole-body diffusion-weighted MRI with apparent diffusion coefficient mapping for early response monitoring in multiple myeloma: preliminary results. AJR Am J Roentgenol 196:W790–W795

    Article  PubMed  Google Scholar 

  26. Giles SL, Messiou C, Collins DJ et al (2014) Whole-body diffusion-weighted MR imaging for assessment of treatment response in myeloma. Radiology 131529

  27. Hillengass J, Zechmann C, Bauerle T et al (2009) Dynamic contrast-enhanced magnetic resonance imaging identifies a subgroup of patients with asymptomatic monoclonal plasma cell disease and pathologic microcirculation. Clin Cancer Res 15:3118–3125

    Article  PubMed  Google Scholar 

  28. Tian J, Fu L, Yin D et al (2014) Does the novel integrated PET/MRI offer the same diagnostic performance as PET/CT for oncological indications? PLoS One 9:e90844

    Article  PubMed Central  PubMed  Google Scholar 

  29. Tofts PS, Brix G, Buckley DL et al (1999) Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10:223–232

    Article  CAS  PubMed  Google Scholar 

  30. Bhutani M, Turkbey B, Tan E et al (2014) Bone marrow angiogenesis in myeloma and its precursor disease: a prospective clinical trial. Leukemia 28:413–416

    Article  CAS  PubMed  Google Scholar 

  31. Hylton N (2006) Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. J Clin Oncol 24:3293–3298

    Article  CAS  PubMed  Google Scholar 

  32. Wasser K, Moehler T, Neben K et al (2004) Dynamic MRI of the bone marrow for monitoring multiple myeloma during treatment with thalidomide as monotherapy or in combination with CED chemotherapy. Rofo 176:1285–1295

    Article  CAS  PubMed  Google Scholar 

  33. Nonomura Y, Yasumoto M, Yoshimura R et al (2001) Relationship between bone marrow cellularity and apparent diffusion coefficient. J Magn Reson Imaging 13:757–760

    Article  CAS  PubMed  Google Scholar 

  34. Dimopoulos MA, Moulopoulos A, Smith T et al (1993) Risk of disease progression in asymptomatic multiple myeloma. Am J Med 94:57–61

    Article  CAS  PubMed  Google Scholar 

  35. Moulopoulos LA, Dimopoulos MA, Smith TL et al (1995) Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol 13:251–256

    CAS  PubMed  Google Scholar 

  36. Mariette X, Zagdanski AM, Guermazi A et al (1999) Prognostic value of vertebral lesions detected by magnetic resonance imaging in patients with stage I multiple myeloma. Br J Haematol 104:723–729

    Article  CAS  PubMed  Google Scholar 

  37. Hillengass J, Fechtner K, Weber MA et al (2010) Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol 28:1606–1610

    Article  PubMed  Google Scholar 

  38. Dhodapkar MV, Sexton R, Waheed S et al (2014) Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120). Blood 123:78–85

    Article  CAS  PubMed  Google Scholar 

  39. Merz M, Hielscher T, Wagner B et al (2014) Predictive value of longitudinal whole-body magnetic resonance imaging in patients with smoldering multiple myeloma. Leukemia

  40. Hillengass J, Ayyaz S, Kilk K et al (2012) Changes in magnetic resonance imaging before and after autologous stem cell transplantation correlate with response and survival in multiple myeloma. Haematologica 97:1757–1760

    Article  PubMed Central  PubMed  Google Scholar 

  41. Bartel TB, Haessler J, Brown TL et al (2009) F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood 114:2068–2076

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Castellani M, Carletto M, Baldini L et al (2010) The prognostic value of F-18 fluorodeoxyglucose bone marrow uptake in patients with recent diagnosis of multiple myeloma: a comparative study with Tc-99m sestamibi. Clin Nucl Med 35:1–5

    Article  PubMed  Google Scholar 

  43. Usmani SZ, Mitchell A, Waheed S et al (2013) Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3. Blood 121:1819–1823

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Derlin T, Weber C, Habermann CR et al (2012) 18F-FDG PET/CT for detection and localization of residual or recurrent disease in patients with multiple myeloma after stem cell transplantation. Eur J Nucl Med Mol Imaging 39:493–500

    Article  PubMed  Google Scholar 

  45. Nanni C, Zamagni E, Celli M et al (2013) The value of 18F-FDG PET/CT after autologous stem cell transplantation (ASCT) in patients affected by multiple myeloma (MM): experience with 77 patients. Clin Nucl Med 38:e74–e79

    Article  PubMed  Google Scholar 

  46. Agool A, Schot BW, Jager PL et al (2006) 18F-FLT PET in hematologic disorders: a novel technique to analyze the bone marrow compartment. J Nucl Med 47:1592–1598

    PubMed  Google Scholar 

  47. Dankerl A, Liebisch P, Glatting G et al (2007) Multiple Myeloma: Molecular Imaging with 11C-Methionine PET/CT – Initial Experience. Radiology 242:498–508

    Article  PubMed  Google Scholar 

  48. Durie BG, Waxman AD, D’Agnolo A et al (2002) Whole-body (18)F-FDG PET identifies high-risk myeloma. J Nucl Med 43:1457–1463

    PubMed  Google Scholar 

  49. Larsen JT, Kumar SK, Dispenzieri A et al (2013) Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia 27:941–946

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Rajkumar SV, Larson D, Kyle RA (2011) Diagnosis of smoldering multiple myeloma. N Engl J Med 365:474–475

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Dispenzieri A, Stewart AK, Chanan-Khan A et al (2013) Smoldering multiple myeloma requiring treatment: time for a new definition? Blood 122:4172–4181

    Article  CAS  PubMed  Google Scholar 

  52. Hanrahan CJ, Christensen CR, Crim JR (2010) Current concepts in the evaluation of multiple myeloma with MR imaging and FDG PET/CT. Radiographics 30:127–142

    Article  PubMed  Google Scholar 

  53. Regelink JC, Minnema MC, Terpos E et al (2013) Comparison of modern and conventional imaging techniques in establishing multiple myeloma-related bone disease: a systematic review. Br J Haematol 162:50–61

    Article  CAS  PubMed  Google Scholar 

  54. Hutchison GB, Shapiro S (1968) Lead time gained by diagnostic screening for breast cancer. J Natl Cancer Inst 41:665–681

    CAS  PubMed  Google Scholar 

  55. Feinleib M, Zelen M (1969) Some pitfalls in the evaluation of screening programs. Arch Environ Health 19:412–415

    Article  CAS  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. M. Bhutani und O. Landgren geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Correspondence to O. Landgren M.D., Ph.D..

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Bhutani, M., Landgren, O. Bildgebung bei „smoldering“ (asymptomatischem) multiplem Myelom. Radiologe 54, 572–581 (2014). https://doi.org/10.1007/s00117-014-2694-7

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