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      Efficacy of lenalidomide in association with cyclophosphamide and dexamethasone in multiple myeloma patient with bilateral retro-orbital localisation

      case-report

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          Abstract

          Extramedullary localisation is an uncommon manifestation in multiple myeloma (MM). Ocular involvement is rare. Here, we describe a relapse of MM with bilateral retro-orbital localisation without any bone involvement with good and rapid response to therapy with lenalidomide, dexamethasone, and cyclophosphamide.

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          Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients.

          M Varettoni, A. Corso, G. Pica … (2010)
          There are few data on the incidence and prognosis of extramedullary (EM) multiple myeloma (MM). There are concerns about a possible increase of EM relapses with the expanding use of high-dose therapy (HDT) and biological agents. The incidence of EM disease, its relationship with prior exposure to HDT or novel agents, and its prognostic impact were analyzed in 1003 MM patients. Based on the different therapies available, three periods were considered: 1971-1993, conventional-dose chemotherapy; 1994-1999, HDT for younger patients; and 2000-2007, introduction of novel agents. Overall, 13% of patients had EM disease, 7% at diagnosis and 6% later. In the 2000-2007 period, there was a significant increase of EM involvement, at diagnosis (P = 0.02) and during follow-up (P = 0.03). The risk of EM spread was not significantly increased after HDT [hazard ratio (HR 0.6)], bortezomib (HR 1.62), or thalidomide/lenalidomide (HR 1.07). EM disease was associated with shorter overall (HR 3.26, P < 0.0001) and progression-free (HR 1.46, P = 0.04) survival. The incidence of EM disease has increased, probably due to the availability of more sensitive imaging techniques and the prolongation of patients' survival. HDT or novel agents seem not to increase the risk of EM disease. EM involvement confers a poor prognosis.
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            Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach.

            R Powles, Carlos Larrea, Joan Bladé … (2011)
            We provide an overview on soft-tissue extramedullary plasmacytomas (EMPs) in multiple myeloma (MM). We reviewed the incidence of EMPs in MM, myeloma bone marrow homing, possible mechanisms of extramedullary spread, and prognosis and response to therapy. The incidence of EMPs is 7% to 18% at MM diagnosis and up to 20% at relapse. The current notion that EMPs are more frequent after treatment with novel agents remains to be proven, especially considering that different patterns of disease recurrence can emerge as patients live longer in the era of novel drugs. Bone marrow genetic abnormalities are not associated with extramedullary spread per se, which also suggests that microenvironmental interactions are key. Possible mechanisms of extramedullary spread include decreased adhesion molecule expression and downregulation of chemokine receptors. EMPs usually show plasmablastic morphology with negative CD56 expression. High-dose therapy with autologous stem-cell transplantation (ASCT) can overcome the negative prognostic impact of extramedullary disease in younger selected patients. EMPs do not typically respond to thalidomide alone, but in contrast, responses to bortezomib have been reported. The incidence of EMPs in patients with MM is high and is associated with poor outcome in patients treated conventionally. A potential first-line treatment option seems to be a bortezomib-containing regimen followed by ASCT, whenever possible. Experimental studies on the mechanisms of myeloma cell adhesion, myeloma growth at extramedullary sites, and drug sensitivity are priorities for this area of continuing therapeutic challenge.
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              Mechanism of action of lenalidomide in hematological malignancies

              Venumadhav Kotla, Swati Goel, Sangeeta Nischal … (2009)
              Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide is a 4-amino-glutamyl analogue of thalidomide that lacks the neurologic side effects of sedation and neuropathy and has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma. Lenalidomide has been shown to be an immunomodulator, affecting both cellular and humoral limbs of the immune system. It has also been shown to have anti-angiogenic properties. Newer studies demonstrate its effects on signal transduction that can partly explain its selective efficacy in subsets of MDS. Even though the exact molecular targets of lenalidomide are not well known, its activity across a spectrum of neoplastic conditions highlights the possibility of multiple target sites of action.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Ecancermedicalscience
                Journal ID (iso-abbrev): Ecancermedicalscience
                Journal ID (publisher-id): ecancermedicalscience
                Title: ecancermedicalscience
                Publisher: Cancer Intelligence
                ISSN (Electronic): 1754-6605
                Publication date Collection: 2013
                Publication date (Electronic): 10 July 2013
                Volume: 7
                Electronic Location Identifier: 331
                Affiliations
                [1 ] Haematology Unit, Nuovo Regina Margherita, Hospital, 00153 Rome, Italy
                [2 ] Histopathology Complex Unit, Santo Spirito Hospital, 00193 Rome, Italy
                Author notes
                Correspondence to: Stefano Felici. sfelici51@ 123456gmail.com
                Article
                Publisher ID: can-7-331
                DOI: 10.3332/ecancer.2013.331
                PMC ID: 3965188
                PubMed ID: 24723969
                SO-VID: d8ac6f5c-f569-4a88-9a3e-952575e5ba80
                Copyright © © the authors; licensee ecancermedicalscience.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 07 March 2013
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: multiple myeloma,extramedullary disease,ocular involvement,lenalidomide
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: multiple myeloma, extramedullary disease, ocular involvement, lenalidomide

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