Magnetic Resonance Imaging of Bone Marrow and its Results as a Criterion for Administration of Maintenance Therapy After Auto-HSCT in Multiple Myeloma Patients

MV Solov’ev, LP Mendeleeva, GA Yatsyk, NS Lutsik, MV Firsova, EG Gemdzhian, VG Savchenko

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Maksim Valer’evich Solov’ev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-31-92; е-mail: maxsolovej@mail.ru

For citation: Solov’ev MV, Mendeleeva LP, Yatsyk GA, et al. Magnetic Resonance Imaging of Bone Marrow and its Results as a Criterion for Administration of Maintenance Therapy After Auto-HSCT in Multiple Myeloma Patients. Clinical oncohematology. 2018;11(4):360–7.

DOI: 10.21320/2500-2139-2018-11-4-360-367


ABSTRACT

Aim. To evaluate the efficacy of maintenance therapy in multiple myeloma (MM) patients after autologous hematopoietic stem cell transplantation (auto-HSCT) based on the results of MRI of bone marrow.

Materials & Methods. The study included 32 MM patients aged 36 to 66 years (median 57 years) with complete remission after a single auto-HSCT. MRI of spine and pelvic bones was performed to identify the nature of bone marrow lesions and to determine the volume of tumor tissue on the day 100 after auto-HSCT. As maintenance therapy after auto-HSCT 14 patients received daily 15 mg lenalidomide in the period from day 1 to day 21 of the 28-day treatment course within 1 year. Monitoring of 18 patients was conducted without maintenance therapy. Statistical analysis included the assessment of progression-free survival (PFS) and relapse risk relationship to clinical and laboratory parameters.

Results. Twenty patients had a positive MRI (tumor volume > 1 cm3). Zero variation of MR signal in bone marrow and detection of a < 1 cm3 tumor were regarded as a negative MRI, which was the case in 12 patients. After reaching the negative MRI the best rates of 2-year PFS were registered: 100 % with maintenance therapy and 84 % without maintenance therapy. In patients with tumor load on MR scans the 2-year PFS significantly (= 0.03) varied and accounted for 80 % in patients who received maintenance therapy vs. 33 % in patients without maintenance therapy. Administration of maintenance therapy after detecting residual tumor on MR scans on day 100 after auto-HSCT has a positive effect on PFS rates. Multivariate analysis confirmed the residual tumor on MR scans of bone marrow to be the most important parameter PFS depends on.

Conclusion. A negative MRI after auto-HSCT is a favourable prognostic factor determining a long-lasting (> 2 years) MM free period, despite the lack of maintenance therapy.

Keywords: multiple myeloma, magnetic resonance imaging (MRI), autologous hematopoietic stem cell transplantation (auto-HSCT), maintenance therapy, minimal residual disease.

Received: May 11, 2018

Accepted: August 29, 2018

Read in PDF 


REFERENCES

  1. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2016;61(1, прил. 2):1–24. doi: 10.18821/0234-5730-2016-61-1(Прил.2). [Mendeleeva LP, Votyakova OM, Pokrovskaya OS, et al. National clinical guidelines on diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2016;61(1, Suppl. 2):1–24. doi: 10.18821/0234-5730-2016-61-1(Прил.2). (In Russ)]

  2. Kumar SK, Rajkumar SV, Dispenzieri A, et Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111(5):2516–20. doi: 10.1182/blood-2007-10-116129.

  3. Mendeleeva LP, Solovev MV, Alexeeva A, at al. Multiple Myeloma in Russia (First Results of the Registration Trial). Blood. 2017;130(Suppl 1):5408.

  4. Passweg JR, Baldomero H, Bader Р, et al. Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant. 2018. doi: 10.1038/s41409-018-0153-1. [Epub ahead of print]

  5. Passweg JR, Baldomero H, Bader P, et al. Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually. Bone Marrow Transplant. 2016;51(6):786–92. doi: 10.1038/bmt.2016.20.

  6. Gay F, Oliva S, Petrucci MT, et al. Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis. Leukemia. 2017;31(8):1727–34. doi: 10.1038/leu.2016.381.

  7. Roussel M, Lauwers-Cances V, Robillard N, et al. Front-Line Transplantation Program With Lenalidomide, Bortezomib, and Dexamethasone Combination As Induction and Consolidation Followed by Lenalidomide Maintenance in Patients With Multiple Myeloma: A Phase II Study by the Intergroupe Francophone du Myelome. J Clin Oncol. 2014;32(25):2712–7. doi: 10.1200/JCO.2013.54.8164.

  8. Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(Suppl 4):iv52–61. doi: 10.1093/annonc/mdx096.

  9. Syed YY. Lenalidomide: A Review in Newly Diagnosed Multiple Myeloma as Maintenance Therapy After ASCT. Drugs. 2017;77(13):1473–80. doi: 10.1007/s40265-017-0795-0.

  10. Goldschmidt H, Lokhorst HM, Mai EK, et al. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018;32(2):383–90. doi: 10.1038/leu.2017.211.

  11. Rosinol L, Oriol A, Teruel AI, et al. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia. 2017;31(9):1922–7. doi: 10.1038/leu.2017.35.

  12. Mellqvist UH, Gimsing P, Hjertner O, et al. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013;121(23):4647–54. doi: 10.1182/blood-2012-11-464503.

  13. Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol. 2012;30(24):2946–55. doi: 10.1200/JCO.2011.39.6820.

  14. McCarthy PL, Owzar K, Hofmeister C, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1770–81. doi: 10.1056/NEJMoa1114083.

  15. Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide Maintenance after Stem-Cell Transplantation for Multiple Myeloma. N Engl J Med. 2012;366(19):1782–91. doi: 10.1056/NEJMoa1114138.

  16. Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905. doi: 10.1056/NEJMoa1402888.

  17. Solovev MV, Mendeleeva LP, Pokrovskaya OS, et al. Maintenance Therapy after Autologous Haematopoietic Stem Cell Transplantation (auto-HSCT) in Multiple Myeloma Patients with and without Minimal Residual Disease (MRD). Blood. 2016;128(22):2260.

  18. Solovev MV, Mendeleeva LP, Pokrovskaya OS, et al. The Duration of MRD-Negative Status in Multiple Myeloma (MM) Patients after Auto-HSCT Is a Criterion for Prolonged Remission without Maintenance Therapy. Blood. 2017;130(Suppl 1):3294.

  19. Dutoit JC, Verstraete KL. Whole-body MRI, dynamic contrast-enhanced MRI, and diffusion-weighted imaging for the staging of multiple myeloma. Skelet Radiol. 2017;46(6):733–50. doi: 10.1007/s00256-017-2609-6.

  20. Latifoltojar A, Hall‐Craggs M, Rabin N, et al. Whole body magnetic resonance imaging in newly diagnosed multiple myeloma: early changes in lesional signal fat fraction predict disease response. Br J Haematol. 2017;176(2):222–33. doi: 10.1111/bjh.14401.

  21. Lasocki A, Gaillard F, Harrison SJ. Multiple myeloma of the spine. Neuroradiol J. 2017;30(3):259–68. doi: 10.1177/1971400917699426.

  22. Bray TJ, Singh S, Latifoltojar A, et al. Diagnostic utility of whole body Dixon MRI in multiple myeloma: A multi-reader study. PLoS One. 2017;12(7):e0180562. doi: 10.1371/journal.pone.0180562.

  23. Sabour S. Whole-body ultra-low dose computed tomography in comparison with spinal magnetic resonance imaging in the assessment of disease in multiple myeloma; Methodological issues on Diagnostic value. Br J Haematol. 2017. doi: 10.1111/bjh.14849. [Epub ahead of print]

  24. Chantry A, Kazmi M, Barrington S, et al. Guidelines for the use of imaging in the management of patients with myeloma. Br J Haematol. 2017;178(3):380–93. doi: 10.1111/bjh.14827.

  25. Moulopoulos LA, Gika D, Anagnostopoulos A, et al. Prognostic significance of magnetic resonance imaging of bone marrow in previously untreated patients with multiple myeloma. Ann Oncol. 2005;16(11):1824–8. doi: 10.1093/annonc/mdi362.

  26. Mai EK, Hielscher T, Kloth JK, et al. Association between magnetic resonance imaging patterns and baseline disease features in multiple myeloma: analyzing surrogates of tumour mass and biology. Eur Radiol. 2016;26(11):3939–48. doi: 10.1007/s00330-015-4195-0.

  27. Walker R, Barlogie B, Haessler J, et al. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol. 2007;25(9):1121–8. doi: 10.1200/JCO.2006.08.5803.

  28. Richardson PG, Holstein SA, Schlossman RL, et al. Lenalidomide in combination or alone as maintenance therapy following autologous stem cell transplant in patients with multiple myeloma: a review of options for and against. Expert Opin Pharmacother. 2017;18(18):1975–85. doi: 10.1080/14656566.2017.1409207.

  29. Pulte ED, Dmytrijuk A, Nie L, et al. FDA Approval Summary: Lenalidomide as Maintenance Therapy After Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma. Oncologist. 2018;23(6):734–9. doi: 10.1634/theoncologist.2017-0440.

  30. Sengsayadeth S, Malard F, Savani BN, et al. Posttransplant maintenance therapy in multiple myeloma: the changing landscape. Blood Cancer J. 2017;7(3):e545. doi: 10.1038/bcj.2017.23.

  31. McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin Oncol. 2017;35(29):3279–89. doi: 10.1200/JCO.2017.72.6679.

  32. Sonneveld P, Avet-Loiseau H, Lonial S, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127(24):2955–62. doi: 10.1182/blood-2016-01-631200.

  33. Sivaraj D, Green MM, Li Z, et al. Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma. Biol Blood Marrow Transplant. 2017;23(2):262–8. doi: 10.1016/j.bbmt.2016.11.010.

  34. Jackson GH, Davies FE, Pawlyn C, et al. Lenalidomide Is a Highly Effective Maintenance Therapy in Myeloma Patients of All Ages; Results of the Phase III Myeloma XI Study. Blood. 2016;128(22):1143.

  35. Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119(4):940–8. doi: 10.1182/blood-2011-09-379164.

  36. Jackson GH, Davies FE, Pawlyn C, et al. Lenalidomide Maintenance Significantly Improves Outcomes Compared to Observation Irrespective of Cytogenetic Risk: Results of the Myeloma XI Trial. Blood. 2017;130(Suppl 1):436.

  37. Mellqvist UH, Gimsing P, Hjertner O, et al. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013;121(23):4647–54. doi: 10.1182/blood-2012-11-464503.

  38. Phase III Studies Present Additional Evidence for REVLIMID® (lenalidomide) as Maintenance Therapy in Multiple Myeloma. Available from: http://ir.celgene.com/releasedetail.cfm?releaseid=1003026 (accessed 2.05.2018).

  39. Соловьев М.В., Менделеева Л.П., Покровская О.С. и др. Множественная миелома: поддерживающая терапия после трансплантации аутологичных гемопоэтических стволовых клеток в зависимости от минимальной остаточной болезни. Терапевтический архив. 2017;89(7):25–31. doi: 10.17116/terarkh201789725-31.

    [Solovyev MV, Mendeleeva LP, Pokrovskaya OS, et al. Multiple myeloma: Maintenance therapy after autologous hematopoietic stem cell transplantation, depending on minimal residual disease. Terapevticheskii arkhiv. 2017;89(7):25–31. doi: 10.17116/terarkh201789725-31. (In Russ)]