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Multiple myeloma gammopathies

European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias

Abstract

The introduction of novel agents in the management of multiple myeloma and related plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström’s macroglobulinemia (WM), AL-amyloidosis, monoclonal immunoglobulin deposition disease (MIDD), POEMS syndrome, and primary plasma cell leukemia. For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease. The management of light chain amyloidosis depends on the presence and severity of heart disfunction. If present, intensification with an autologous stem cell transplantation (ASCT) is not recommended. Further aggregation of misfolded light chains could be prevented by doxycycline or monoclonal antibodies targeting amyloid deposits. Initial treatment generally consists of melphalan/dexamethasone or bortezomib-based regimens. For relapsing patients, one can consider proteasome inhibitors, immunomodulatory agents, melphalan or daratumumab. Because intact or light-chain immunoglobulins are also the culprits for MIDD, the small monoclonal plasma cells' clones should be treated and generally respond well to bortezomib-based treatment. POEMS syndrome is a well-defined clinical entity that can present as solitary bone lesions or disseminated disease. Radiation therapy is used for patients with localized disease and result in long-lasting response. Systemic treatment should be proposed to patients with disseminated disease, but regimens that can worsen a pre-existing polyneuropathy should be avoided. PPCL is located at the other end of the spectrum of plasma cell disorders and is associated with an aggressive disease course and poor prognosis. It requires an imminent, multi-phase and novel agents-based therapy, including induction, ASCT, consolidation and maintenance, with short treatment-free intervals. Patients not eligible for transplant procedures require personalized, intensive therapeutic approach. Allogeneic stem cell transplantation can be used in selected patients.

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Correspondence to Evangelos Terpos.

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Maria Gavriatopoulou has received honoraria for advisory boards and honoraria from Amgen, Takeda, and Janssen. Pellegrino Musto has received honoraria for advisory boards and honoraria from Janssen, Celgene, Takeda, Amgen, and Bristol-Myers Squibb. Efstathios Kastritis has received honoraria for advisory boards and honoraria from Janssen, Celgene, Amgen, Takeda, and Prothena. Niels van de Donk has received research funding and honoraria for participating in advisory boards from Janssen, Celgene, Bristol-Myers Squibb, and Amgen. Francesca Gay has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, and Takeda, and honoraria for participation in advisory boards from Janssen, Amgen, Celgene, Roche, and Takeda. Roman Hájek has received consultancy fees, research funding, and honoraria for participation in advisory boards from Amgen, Takeda, Bristol-Myers Squibb, Celgene, Novartis, and Janssen. Sonja Zweegman has received honoraria for participating in advisory boards and research funding from Janssen, Celgene, Novartis, and Takeda. Meletios A. Dimopoulos has received consultancy fees and honoraria from Celgene, Onyx, Janssen, Novartis, and Amgen, and honoraria for participation in advisory boards from Amgen, Takeda, Celgene, and Janssen. Hermann Einsele has received speakers’ honoraria and honoraria for participation in advisory boards for Celgene, Janssen, Amgen, Bristol-Myers Squibb, and Novartis, and consultancy fees or honoraria from Celgene, Janssen, Bristol-Myers Squibb, and Amgen. Pieter Sonneveld has received honoraria for participating in advisory boards and honoraria from Amgen, Bristol-Myers-Squibb, Celgene, Janssen, and Karyopharm and research support from Amgen, Celgene, Janssen, Karyopharm, and SkylineDx. Monika Engelhardt has received educational grants from Celgene, Janssen, Amgen, Takeda and MSD. Evangelos Terpos has received honoraria from Janssen, Amgen, Takeda, Abbvie, Bristol-Myers Squibb, PharmaMar, and Celgene, research funding from Amgen, Genesis, Janssen, Novartis, and Takeda, honoraria for participation in advisory boards from Takeda, as well as honoraria for participation in the data monitoring committee from Celgene. Jo Caers, Giampaolo Merlini, Ute Hegenbart, Benedetto Bruno, Christian Straka and Mario Boccadoro have no relevant conflicts to disclose.

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Gavriatopoulou, M., Musto, P., Caers, J. et al. European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias. Leukemia 32, 1883–1898 (2018). https://doi.org/10.1038/s41375-018-0209-7

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