Skip to main content
Top
Published in: European Radiology 12/2010

01-12-2010 | Oncology

Early response assessment in patients with multiple myeloma during anti-angiogenic therapy using arterial spin labelling: first clinical results

Authors: Michael Fenchel, Marina Konaktchieva, Katja Weisel, Sabina Kraus, Harald Brodoefel, Claus D. Claussen, Marius Horger

Published in: European Radiology | Issue 12/2010

Login to get access

Abstract

Objective

To determine if arterial-spin-labelling (ASL) MRI can reliably detect early response to anti-angiogenic therapy in patients with multiple myeloma by comparison with clinical/haematological response.

Methods

Nineteen consecutive patients (10 men; mean age 63.5 ± 9.1 years) were included in the present study. Inclusion criteria were diagnosis of stage III multiple myeloma and clinical indication for therapeutical administration of bortezomib or lenalidomide. We performed MRI on 3.0T MR in the baseline setting, 3 weeks after onset of therapy and after 8 weeks. Clinical responses were determined on the basis of international uniform response criteria in correlation with haematological parameters and medium-term patient outcome. MRI studies were performed after approval by the local institutional review board.

Results

Fifteen patients responded to anti-myeloma therapy; 4/19 patients were non-responders to therapy. Mean tumour perfusion assessed by ASL-MRI in a reference lesion was 220.7 ± 132.5 ml min−1 100 g−1 at baseline, and decreased to 125.7 ± 86.3 (134.5 ± 150.9) ml min−1 100 g−1 3 (8) weeks after onset of therapy (P < 0.02). The mean decrease in paraproteinaemia at week 3 (8) was 52.3 ± 47.7% (58.2 ± 58.7%), whereas β2-microglobulinaemia decreased by 20.3 ± 53.1% (23.3 ± 57.0%). Correlation of ASL perfusion with outcome was significant (P = 0.0037).

Conclusion

ASL tumour perfusion measurements are a valuable surrogate parameter for early assessment of response to novel anti-angiogenic therapy.
Literature
1.
go back to reference Kumar S, Fonseca R, Dispenzieri A et al (2002) Bone marrow angiogenesis in multiple myeloma: effect of therapy. Br J Haematol 119:665–671CrossRefPubMed Kumar S, Fonseca R, Dispenzieri A et al (2002) Bone marrow angiogenesis in multiple myeloma: effect of therapy. Br J Haematol 119:665–671CrossRefPubMed
2.
go back to reference Pruneri G, Ponzoni M, Ferreri AJ et al (2002) Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol 118:817–820CrossRefPubMed Pruneri G, Ponzoni M, Ferreri AJ et al (2002) Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol 118:817–820CrossRefPubMed
3.
go back to reference Lin C, Luciani A, Belhadj K et al (2009) Patients with plasma cell disorders examined at whole-body dynamic contrast-enhanced MR imaging: initial experience. Radiology 250:905–915CrossRefPubMed Lin C, Luciani A, Belhadj K et al (2009) Patients with plasma cell disorders examined at whole-body dynamic contrast-enhanced MR imaging: initial experience. Radiology 250:905–915CrossRefPubMed
4.
go back to reference Pollock JM, Tan H, Kraft RA et al (2009) Arterial spin-labeled MR perfusion imaging: clinical applications. Magn Reson Imaging Clin N Am 17:315–338CrossRefPubMed Pollock JM, Tan H, Kraft RA et al (2009) Arterial spin-labeled MR perfusion imaging: clinical applications. Magn Reson Imaging Clin N Am 17:315–338CrossRefPubMed
5.
go back to reference Blade J, Samson D, Reece D et al (1998) Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 102:1115–1123CrossRefPubMed Blade J, Samson D, Reece D et al (1998) Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 102:1115–1123CrossRefPubMed
6.
go back to reference Montazel J, Divine M, Lepage E et al (2003) Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging. Radiology 229:703–709CrossRefPubMed Montazel J, Divine M, Lepage E et al (2003) Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging. Radiology 229:703–709CrossRefPubMed
7.
go back to reference Takeuchi M, Matsuzaki K Nishitani H (2009) Diffusion-weighted magnetic resonance imaging of endometrial cancer: differentiation from benign endometrial lesions and preoperative assessment of myometrial invasion. Acta Radiol 1:1–7 Takeuchi M, Matsuzaki K Nishitani H (2009) Diffusion-weighted magnetic resonance imaging of endometrial cancer: differentiation from benign endometrial lesions and preoperative assessment of myometrial invasion. Acta Radiol 1:1–7
8.
go back to reference Kyle RA, Rajkumar SV (2004) Multiple myeloma. N Engl J Med 28(351):1860–1873CrossRef Kyle RA, Rajkumar SV (2004) Multiple myeloma. N Engl J Med 28(351):1860–1873CrossRef
10.
go back to reference Attal M, Harousseau JL, Facon T et al (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502CrossRefPubMed Attal M, Harousseau JL, Facon T et al (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502CrossRefPubMed
11.
go back to reference Hideshima T, Anderson KC (2002) Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat Rev Cancer 2:927–937CrossRefPubMed Hideshima T, Anderson KC (2002) Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat Rev Cancer 2:927–937CrossRefPubMed
12.
go back to reference Richardson PG, Sonneveld P, Schuster MW et al (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498CrossRefPubMed Richardson PG, Sonneveld P, Schuster MW et al (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498CrossRefPubMed
13.
go back to reference Richardson PG, Barlogie B, Berenson J et al (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348:2609–2617CrossRefPubMed Richardson PG, Barlogie B, Berenson J et al (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348:2609–2617CrossRefPubMed
14.
go back to reference Richardson PG, Schlossman RL, Weller E et al (2002) Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 100:3063–3067CrossRefPubMed Richardson PG, Schlossman RL, Weller E et al (2002) Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 100:3063–3067CrossRefPubMed
15.
go back to reference Davies FE, Raje N, Hideshima T et al (2001) Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 98:210–216CrossRefPubMed Davies FE, Raje N, Hideshima T et al (2001) Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 98:210–216CrossRefPubMed
16.
go back to reference Hideshima T, Chauhan D, Shima Y et al (2000) Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 96:2943–2950PubMed Hideshima T, Chauhan D, Shima Y et al (2000) Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 96:2943–2950PubMed
17.
go back to reference Horger M, Pereira P, Claussen CD et al (2008) Hyperattenuating bone marrow abnormalities in myeloma patients using whole-body non-enhanced low-dose MDCT: correlation with haematological parameters. Br J Radiol 81:386–396CrossRefPubMed Horger M, Pereira P, Claussen CD et al (2008) Hyperattenuating bone marrow abnormalities in myeloma patients using whole-body non-enhanced low-dose MDCT: correlation with haematological parameters. Br J Radiol 81:386–396CrossRefPubMed
18.
go back to reference Walker R, Barlogie B, Haessler J et al (2007) Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol 25:1121–1128CrossRefPubMed Walker R, Barlogie B, Haessler J et al (2007) Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol 25:1121–1128CrossRefPubMed
19.
go back to reference Angtuaco EJ, Fassas AB, Walker R et al (2004) Multiple myeloma: clinical review and diagnostic imaging. Radiology 231:11–23CrossRefPubMed Angtuaco EJ, Fassas AB, Walker R et al (2004) Multiple myeloma: clinical review and diagnostic imaging. Radiology 231:11–23CrossRefPubMed
20.
go back to reference Warmuth C, Gunther M, Zimmer C (2003) Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging. Radiology 228:523–532CrossRefPubMed Warmuth C, Gunther M, Zimmer C (2003) Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging. Radiology 228:523–532CrossRefPubMed
21.
go back to reference Schor-Bardach R, Alsop DC, Pedrosa I et al (2009) Does arterial spin-labeling MR imaging–measured tumor perfusion correlate with renal cell cancer response to antiangiogenic therapy in a mouse model? Radiology 251:731–742CrossRefPubMed Schor-Bardach R, Alsop DC, Pedrosa I et al (2009) Does arterial spin-labeling MR imaging–measured tumor perfusion correlate with renal cell cancer response to antiangiogenic therapy in a mouse model? Radiology 251:731–742CrossRefPubMed
22.
go back to reference Rahmouni A, Montazel JL, Divine M et al (2003) Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging. Radiology 229:710–717CrossRefPubMed Rahmouni A, Montazel JL, Divine M et al (2003) Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging. Radiology 229:710–717CrossRefPubMed
Metadata
Title
Early response assessment in patients with multiple myeloma during anti-angiogenic therapy using arterial spin labelling: first clinical results
Authors
Michael Fenchel
Marina Konaktchieva
Katja Weisel
Sabina Kraus
Harald Brodoefel
Claus D. Claussen
Marius Horger
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
European Radiology / Issue 12/2010
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-010-1870-z

Other articles of this Issue 12/2010

European Radiology 12/2010 Go to the issue