doi:10.1111/ejh.12429

European Journal of Haematology 94 (95)

EDITORIAL

Has the time come to reevaluate prognostic factors and to rebuild staging systems for Multiple Myeloma? During the last decade, the inclusion of new drugs into routine clinical practice for the treatment of multiple myeloma (MM) has improved patients’ outcome. The so-called new drugs, namely thalidomide, bortezomib, and lenalidomide, interfere with biological disease mechanisms leading to transcription factors’ inhibition, neoangiogenesis downregulation, immunomodulation and other. However, MM prognosis remains highly variable and unfortunately, some patients still succumb from disease after a relatively short life span period. With the additional recent introduction of next generation novel agents and monoclonal antibodies targeting microenvironmental and plasma cell factors, patients’ specific approaches may become possible; indeed, in such case, therapeutic decisions should be guided by accurate prognostic factors and systems. However, many well-known disease markers were established before the broad usage of novel agents and were not validated in the era of new antimyeloma treatment modalities. In the present issue, Iriuchishima et al. (1) observed that the predictive power of various prognostic factors was shadowed by the administration new agents. Thus neither serum creatinine ≥2 mg/dL, abnormal LDH, serum calcium above normal, light chain restriction and extensive plasma cell infiltration, nor even the presence of an abnormal karyotype was predictive of a worse outcome in patients treated with new drugs. In addition, in their cohort of symptomatic MM patients with half of them treated with new drugs and the others conventionally, they found no stage-dependent difference in survival according to the International Staging System (ISS) in the group treated with novel agents, while indeed the same was not true for patients treated with conventional chemotherapy as well as for those that received high-dose treatment with autologous stem cell transplantation. In this study, anemia and the presence of plasmacytoma were the only independent prognostic factors for patients treated with new agents, and therefore, the authors built a prognostic system that was able to separate patients into prognostic groups with different outcome. The occurrence of plasmacytomas was recorded in the aforementioned study at a higher frequency than in most published series, possibly because they used sensitive methods for their detection (MRI and PET scan). This strengthens the need of using more accurate radiology methods than X-rays for bone disease and plasmacytomas assessment; low-dose intensity whole body computed tomography could constitute a valuable alternative (2). The ability of some novel agents to overcome the adverse impact of well-established prognostic factors have been

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shown by several investigators (3, 4). Relevant studies mainly concern bortezomib that was shown able to reverse the negative effect of classical prognostic markers such as age, anemia, impaired renal function, hypercalcemia, serumfree light chains and even the impact of unfavorable genetic alterations (del13q, t(4;14), amp CKS1B) while it does not completely undo the impact of del17p. New technologies have allowed a better comprehension of the molecular basis of the disease, and stratification models based on them may allow the early identification of high-risk patients in the new era. However, sophisticated molecular techniques are not accessible in routine clinical practice. Precisely, the simplicity and clinical availability of the prognostic system proposed by Iriuchishima et al. (1) is rendering it appealing and worth testing it in larger series. References 1. Iriuchishima H, Saitoh T, Handa H, et al. A new staging system to predict prognosis of patients with multiple myeloma in an era of novel therapeutic agents. Eur J Haematol 2014; doi: 10.1111/ejh.12407 2. Ippolito D, Besostri V, Bonaffini PA, Rossini F, Di Lelio A, Sironi S. Diagnostic value of whole-body low-dose computed tomography (WBLDCT) in bone lesions detection in patients with multiple myeloma (MM). Eur J Radiol 2013;82:2322–7. 3. Bergsagel PL, Mateos MV, Gutierrez NC, Rajkumar VS, San Miguel J. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma. Blood 2013;121:884–92. 4. Maltezas D, Dimopoulos MA, Katodritou I, et al. Re-evaluation of prognostic markers including staging, serum free light chains or their ratio and serum lactate dehydrogenase in multiple myeloma patients receiving novel agents. Hemat Oncol 2013;31:96–102.

Marie-Christine Kyrtsonis Hematology Section of First Department of Propaedeutic Internal Medicine, University of Athens’ Medical School, Athens, Greece

Correspondence Marie-Christine Kyrtsonis, MD, Hematology Section of First Department of Propaedeutic Internal Medicine, University of Athens’ Medical School, Athens 11527, Greece. Tel: +30 2107462183; Fax: +30 2107462224; e-mail: [email protected]

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Has the time come to reevaluate prognostic factors and to rebuild staging systems for multiple myeloma?

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