Cerchione, Claudio (2017) Management of Relapsed/Refractory Multiple Myeloma with Bendamustine-Bortezomib-Dexamethasone. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Lingua: English
Title: Management of Relapsed/Refractory Multiple Myeloma with Bendamustine-Bortezomib-Dexamethasone
Cerchione, Claudioclaudiocerc@hotmail.com
Date: 10 April 2017
Number of Pages: 154
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Clinica e Chirurgia
Dottorato: Terapie avanzate medico-chirurgiche
Ciclo di dottorato: 29
Coordinatore del Corso di dottorato:
Di Minno, Giovannigiovanni.diminno@unina.it
Date: 10 April 2017
Number of Pages: 154
Uncontrolled Keywords: Multiple Myeloma, Bendamustine, Bortezomib, rrMM
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Area 06 - Scienze mediche > MED/06 - Oncologia medica
Area 06 - Scienze mediche > MED/09 - Medicina interna
Area 06 - Scienze mediche > MED/15 - Malattie del sangue
Additional Information: Claudio Cerchione, nato a Napoli il 19/02/1984, laureato in Medicina e Chirurgia presso l'Università degli Studi di Napoli Federico II (110 e lode, 22/07/2008), Specializzazione in Ematologia presso l'Università degli Studi di Napoli Federico II (50 e lode, 01/07/2014),
Date Deposited: 27 Apr 2017 10:13
Last Modified: 14 Mar 2018 11:56
URI: http://www.fedoa.unina.it/id/eprint/11846
DOI: 10.6093/UNINA/FEDOA/11846


Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. It accounts for approximately 1.8% of all hematologic and solid cancers and slightly > 15% of hematologic malignancies in the United States. MM is most frequently diagnosed among people aged 65 to 74 years (median age 69 years). During 2016, the American Cancer Society estimated that 30.330 new cancer cases occurred in USA, with 12.650 deaths. Over the past decade, statistical analysis show that the rates for new MM cases have been increasing an average of 0.8% each year. However, these analysis also reveal that death rates have been declining an average of 0.8% each year (period 2004-2013) thanks to the availability of newer and more effective treatment options. MM is typically sensitive to different classes of cytotoxic drugs, both as frontline treatment and as treatment for relapsed disease. Unfortunately, even if responses are typically durable, nowadays MM is not considered curable with current approaches. However, treatment of MM has been rapidly evolving, due to the introduction of new classes of drugs, such as proteasome inhibitors, immunomodulatory drugs (IMIDs), histone deacetylase inhibitors and monoclonal antibodies and new indications for old classes of drugs, such as alkylating agents. Moreover, there is increasing understanding of MM tumor biology, creating the rational for new combinations of drugs and new therapies development. Discover of the associated cytogenetic abnormalities confirm the hypothesis that MM is a heterogeneous disease, suggesting that risk-adapted therapies and individualizing treatment will further help to improve patient management. Bendamustine is a molecule largely adopted in the past as effective chemotherapeutic agent in several types of hematological and non-hematological malignancies. Its unique mechanism of action, both as alkylating agent and antimetabolite, probably accounts for its wide efficacy profile also in the treatment of relapsing/refractory multiple myeloma. In this specific clinical setting, in which patients experience several therapy lines and have poor prognosis, bendamustine combined with bortezomib and dexamethasone, is emerging as an effective salvage therapy, also in the era of new drugs. In fact, despite the introduction of so-called novel agents, such as second generation proteasome inhibitors (carfilzomib) or third generation immunomodulatory drugs (pomalidomide), many trials have demonstrated that bendamustine in combination with other agents is also a valid therapeutic option as these mentioned above. This retrospective, observational study aimed to evaluate, in a real-life setting, a cohort of heavily pre-treated patients affected by relapsing/refractory multiple myeloma, whose salvage therapy consisted in courses of bendamustine-bortezomib-dexamethasone. Efficacy and safety data were evaluated, focusing especially on effectiveness of this regimen on previously bortezomib-refractory patients and on its tolerability. Data on efficacy and safety of our real-life experience were highly comparable to those of major trials adopting the same regimen in the same clinical setting, demonstrating how it is a feasible salvage therapeutic option, in a context of poor treatment choices. Moreover, our data revealed how bendamustine addition could overcome a previous pharmacological refractoriness to bortezomib, leading to clinical response also those patients already treated with this proteasome inhibitor.


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