Int J Clin Oncol DOI 10.1007/s10147-015-0809-4

INTRODUCTION TO REVIEW ARTICLES

Recent advances in multiple myeloma Yutaka Kohgo 

Received: 16 February 2015 / Accepted: 19 February 2015 © Japan Society of Clinical Oncology 2015

Multiple myeloma (MM) is an incurable hematologic malignancy derived from plasma cells and is characterized by a variety of clinical symptoms such as anemia, hypercalcemia, renal dysfunction and bone lesions. MM is reported to be increasing annually in both males and females, especially in the elderly. A further increase of MM patients is predicted due to growth in the elderly population. MM is thought to be preceded by a premalignant disorder—monoclonal gammopathy of undetermined significance (MGUS)—which shows the monoclonal proliferation of plasma cells without any clinical symptoms and is frequently diagnosed by accidental blood examination. Because the annual rate of progression from MGUS to MM is estimated to be approximately 0.5–1.0 %, careful follow-up is required. Myeloma cells, whose biological behavior is similar to that of normal plasma cells, show extensive somatic hypermutation of immunoglobulin genes and the maintenance of myeloma cell viability and cell proliferation requires interaction with other cells in the bone marrow [1]. Furthermore, clonal proliferation of myeloma cells in the course of multistep hypermutation of immunoglobulin causes additional genetic events, which result in the heterogeneity of myeloma cells. These heterogeneities have recently been found to be closely related with the treatment responses and clinical outcomes of individual myelomas. For example, patients with either deletion of chromosome 17p or amplification of chromosome 1q or t (4;14) had poor clinical prognosis. The basic research on the role of microenvironmental

Y. Kohgo (*)  Division of Gastroenterology and Hematology/Oncology, Department on Internal Medicine, Asahikawa Medical University, 2‑1, Midorigaoka‑Higashi, Asahikawa, Hokkaido 078‑8510, Japan e-mail: yk1950@asahikawa‑med.ac.jp

interactions between myeloma cells and bone marrow cells revealed the importance of cell adhesion, angiogenesis, cytokine-like IL-6 and growth factors for myeloma cell growth. Accumulated knowledge of the biology of MM focused on the development of noble drugs such as thalidomide, lenalidomide and bortezomib, all of which target these myeloma cell-growth environments. Compared with the remarkable therapeutic improvement in leukemia and malignant lymphoma, progress in MM therapy has been delayed. Since the introduction of melphalan and prednisolone (MP) therapy for MM in the 60s, many combination chemotherapies have been developed. However, a marked extension of overall survival has not been achieved despite the severe adverse effects, and MP therapy has been considered to be the standard therapy against MM for >40 years. High-dose chemotherapy supported by autologous stem cell transplantation showed a significant survival advantage to some extent for young adults. Dramatic therapeutic progress has been made in recent years by newly developed molecular-targeted agents such as proteasome inhibitors and immunomodulatory agents [2–4]. In addition, more potent next-generation drugs are under development and are expected to be commercially available in the near future. Advances in MM therapy with molecular-targeted agents also contributed to significant progress in the investigation and understanding of the biology of MM. Activation of both clinical and basic research in MM are leading to further advances in new drug development. In this issue of International Journal of Clinical Oncology, two experts review the recent advances in the basic molecular knowledge and clinical treatment of multiple myeloma. These review articles will provide valuable information in this field and help readers to understand the current advances in this hematologic malignancy.

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Conflict of interest  The authors declare that they have no conflict of interest.

References 1. Hideshima T, Mitsiades C, Tonon G et al (2007) Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer 7:585–598

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Int J Clin Oncol 2. Kumar SK, Rajkumar SV, Dispenzieri A et al (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111:2516–2520 3. Dimopoulos M, Spencer A, Attal M et al (2009) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357:2123–2132 4. Richardson PG, Sonneveld P, Schuster MW et al (2005) Assessment of proteasome inhibition for extending remissions (APEX) investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498

Recent advances in multiple myeloma.

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