Clinical features of multiple myeloma patients with isolated extramedullary relapse

Abstract

This study sought to analyze the clinical features and prognosis of multiple myeloma with isolated extramedullary relapse and with the absence of systemic progression. The clinical features and outcome were retrospectively analyzed in six multiple myeloma patients. These patients had secretory multiple myeloma at diagnosis. When relapsed, the dissociation between medullary and extramedullary response was detected. The serum or urine monoclonal component was extremely low or absent. The plasma cells in bone marrow were <5%. All patients received new targeted therapies (thalidomide or bortezomib) before extramedullary relapse. It is difficult to achieve second remission for them. Even in those showing response, the duration of response was extremely short. The median of overall survival from diagnosis and from extramedullary relapse was 19 months and 6 months, respectively. The overall survival was significantly shorter compared to the patients without extramedullary involvement (84 months, P= 0.001). These patients exhibited a special and rare relapse pattern. Patients with this relapse pattern were resistant to current therapies, including novel targeted agents and associated with poor prognosis.

Keywords

multiple myeloma / extramedullary / clinical feature / prognosis

References

[1] Mahindra A, Hideshima T, Anderson KC. Multiple myeloma: biology of the disease[J]. Blood Rev, 2010, 24 (Suppl 1): S5–11.

[2] Usmani SZ, Heuck C, Mitchell A, Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents[J]. Haematologica, 2012, 97(11): 1761–1767.

[3] Rasche L, Bernard C, Topp MS, Features of extramedullary myeloma relapse: high proliferation, minimal marrow involvement, adverse cytogenetics: a retrospective single-center study of 24 cases[J]. Ann Hematol, 2012, 91(7):1031–1037.

[4] Moreau P, Polliack A. Extramedullary multiple myeloma: extraosseous relapse is extra “bad news,” but why[J]. Leuk Lymphoma, 2013, 54(7): 1349–1350.

[5] Hayes DW, Bennett WA, Heck FJ. Extramedullary lesions in multiple myeloma; review of literature and pathologic studies[J]. Ama Arch Pathol, 1952, 53(3): 262–272.

[6] Durie BG, Harousseau JL, Miguel JS, International uniform response criteria for multiple myeloma[J]. Leukemia, 2006, 20(9): 1467–1473.

[7] Blade J, de Larrea C F, Rosinol L, Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach[J]. J Clin Oncol, 2011, 29(28): 3805–3812.

[8] Ghobrial IM. Myeloma as a model for the process of metastasis: implications for therapy[J]. Blood, 2012, 120(1): 20–30.

[9] Varettoni M, Corso A, Pica G, Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients[J]. Ann Oncol 2010, 21(2): 325–330.

[10] Short KD, Rajkumar SV, Larson D, Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma[J]. Leukemia, 2011, 25(6): 906–908.

[11] Dawson MA, Patil S, Spencer A. Extramedullary relapse of multiple myeloma associated with a shift in secretion from intact immunoglobulin to light chains[J]. Haematologica, 2007, 92(1): 143–144.

[12] Pirrotta MT, Gozzetti A, Cerase A, Unusual discordant responses in two multiple myeloma patients during bortezomib treatment[J]. Onkologie, 2008, 31(1-2): 45–47.

[13] Rosinol L, Cibeira MT, Blade J, Extramedullary multiple myeloma escapes the effect of thalidomide[J]. Haematologica, 2004, 89(7): 832–836.

[14] Gozzetti A, Marchini E, Banchi B, Extramedullary multifocal plasmacytoma relapse in multiple myeloma[J]. Leuk Res, 2012, 36(1): e34–6.

[15] Avigdor A, Raanani P, Levi I, Extramedullary progression despite a good response in the bone marrow in patients treated with thalidomide for multiple myeloma[J]. Leuk Lymphoma, 2001, 42(4): 683–687.

[16] Blade J, Perales M, Rosinol L, Thalidomide in multiple myeloma: lack of response of soft-tissue plasmacytomas[J]. Br J Haematol, 2001, 113(2): 422–424.

[17] Biagi JJ, Mileshkin L, Grigg AP, Efficacy of thalidomide therapy for extramedullary relapse of myeloma following allogeneic transplantation[J]. Bone Marrow Transplant, 2001, 28(12): 1145–1150.

[18] Laura R, Cibeira MT, Uriburu C, Bortezomib: an effective agent in extramedullary disease in multiple myeloma[J]. Eur J Haematol, 2006, 76(5): 405–408.

[19] Paubelle E, Coppo P, Garderet L, Complete remission with bortezomib on plasmocytomas in an end-stage patient with refractory multiple myeloma who failed all other therapies including hematopoietic stem cell transplantation: possible enhancement of graft-vs-tumor effect[J]. Leukemia, 2005, 19(9): 1702–1704.

[20] Nakazato T, Mihara A, Ito C, Lenalidomide is active for extramedullary disease in refractory multiple myeloma[J]. Ann Hematol, 2012, 91(3): 473–474.

[21] Calvo-Villas JM, Alegre A, Calle C, Lenalidomide is effective for extramedullary disease in relapsed or refractory multiple myeloma[J]. Eur J Haematol, 2011, 87(3): 281–284.

[22] Terpos E, Rezvani K, Basu S, Plasmacytoma relapses in the absence of systemic progression post- high-dose therapy for multiple myeloma[J]. Eur J Haematol, 2005, 75(5): 376–383.

[23] Fassas AB, Ward S, Muwalla F, Myeloma of the central nervous system: strong association with unfavorable chromosomal abnormalities and other high-risk disease features[J]. Leuk Lymphoma, 2004, 45(2): 291–300.

[24] Zeiser R, Deschler B, Bertz H, Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome[J]. Bone Marrow Transplant, 2004, 34(12): 1057–1065.

Acknowledgements

This work was supported by Foundation of National Natural Science Foundation of China (81241074, 81071946 and 81302040), Natural Science Foundation of Jiangsu Province (BK2012485), Jiangsu Province's Medical Elite Program (RC201148); a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, Clinical Research Program from Health Ministry of China (Key project 2010 to 2012), and Scientific Research Program for Public Interests from the Health Ministry of China (No. 201202017).

RIGHTS & PERMISSIONS

2017 2017 by the Journal of Biomedical Research.