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Intrapleural Bortezomib for the Therapy of Myelomatous Pleural Effusion: A Case Report

Intrapleural Bortezomib for the Therapy of Myelomatous Pleural Effusion: A Case Report Hindawi Publishing Corporation Case Reports in Immunology Volume 2012, Article ID 978479, 3 pages doi:10.1155/2012/978479 Case Report Intrapleural Bortezomib for the Therapy of Myelomatous Pleural Effusion: A Case Report 1, 2 1, 2 1, 3 1 1 Magdalena Klanova, Pavel Klener, Marek Trneny, Jan Straub, and Ivan Spicka 1st Department of Medicine and Clinical Department of Hematology, the General Teaching Hospital, Charles University in Prague, Prague, Czech Republic Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic Institute of Hematology and Blood Transfusion, Prague, Czech Republic Correspondence should be addressed to Ivan Spicka, spicka@cesnet.cz Received 18 August 2012; Accepted 20 September 2012 Academic Editors: N. Martinez-Quiles, H. Narimatsu, M. M. Nogueras, and H. L. Trivedi Copyright © 2012 Magdalena Klanova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Myelomatous pleural effusion (MPE) is an extremely rare manifestation of multiple myeloma (MM). We present a case of MPE in a patient with IgG-κ MM treated with intrapleural bortezomib with systemic bortezomib-based therapy. Although we observed good local response, the patient succumbed due to systemic myeloma progression. 1. Introduction right ovary, multiple osteolytic lesions in the skull and ribs, and bilateral axillar lymphadenopathy. Immunohistochem- Myelomatous pleural effusion is an extremely rare manifes- ical analysis of the breast tumor biopsy revealed plasmacy- tation of multiple myeloma and only a few cases have been toma/multiple myeloma. Bone marrow examination by tre- reported to date [1]. MPE in patients with MM is often phine biopsy revealed 30% infiltration with atypical plasma associated with high-risk disease and poor prognosis despite cells. Cytogenetic studies including FISH showed a dele- aggressive treatment. There is no standard treatment strategy tion of chromosome 13 and amplification of 1q21 and 1q26 for MPE and the majority of cases of MM presenting with genomic regions. On admission the total plasma protein MPE were associated with resistance to therapy [2]. Borte- was 106 g/L, albumin 40 g/L, urea 5.7 mmol/L, creatinine zomib (the dipeptidylboronic acid analogue, proteasome 74 umol/L, calcium 2.12 mmol/L, LDH 3.7 ukat/L (normal inhibitor) belongs now to backbone antimyeloma drugs. The values 2,2–3,75 ukat/L), and β-2 microglobulin 3.0 mg/L data concerning intrapleural administration of bortezomib is (normal values 1.0–2,4 mg/L). The international staging sys- scarce. We present a case of MPE in a patient with IgG-κ MM tem (ISS) score was 1. Serum protein electrophoresis with treated with intrapleural bortezomib and concomitantly with immunofixation confirmed monoclonal gammopathy IgG-κ systemic bortezomib-based-combined therapy. 44 g/L. Initially, the patient was treated with cyclophospha- mide, thalidomide, and dexamethasone (CTD), but achieved no objective response (stable disease). In the second line ther- 2. Case History apy bortezomib (Velcade) was added (VTD combination) A 43-year-old female initially presented to the hospital in but due to side effects (severe myopathy) dexamethasone had November 2009 with a dry cough, dyspnea, and left chest to be shortly discontinued. pain. The chest X-ray showed bilateral pneumonia. The com- In July 2010, after 2 VT cycles, the CT scan showed a puter tomography demonstrated a massive tumor involving progression of extranodal masses with massive left pleural the left breast and chest cavity, a tumor in the uterus and effusion (Figure 1(a)). The flow-cytometry analysis of pleural 2 Case Reports in Immunology (a) (b) Figure 1: (a) Chest X-ray of patient showing massive left pleural effusion and (b) reduction of the pleural effusion after two doses of intrapleural bortezomib. effusion demonstrated infiltration with atypical plasma cells could be variable. Pleural effusion is an untypical finding in thereby confirming the diagnosis of MPE. Repeated evacu- myeloma patients affecting approximately 6% of the cases ations of the pleural fluid resulted only in short alleviations [1]. The pathogenesis most frequently involves congestive followed by rapid replenishment of the MPE. The patient was heart failure due to amyloidosis and cardiac disease in the indicated to third-line therapy and received 1 modified cycle older myeloma population [5, 6]. MPE itself due to involve- of bortezomib, doxorubicin, and dexamethasone (PAD), in ment of the pleura is extremely rare and only a few cases have which, on days 8 and 11, one-half of the bortezomib dose been reported to date. Kintzer et al. reported 0.8% cases of (i.e., 0.75 mg/m ) was administered intrapleurally and the MPE from 958 patients with MM [1]. MPE usually occurs other half (i.e., 0.75 mg/m ) intravenously. The patient thus as a late complication of MM in the course of the disease received two doses of intrapleural bortezomib (0.75 mg/m ) progression and is associated with very poor prognosis. A three days apart, namely, in an attempt to mitigate the survival rate of less than 4 months has been reported in the symptoms associated with pleural effusion refractory to few cases of MPE despite aggressive treatment [6]. repeated thoracocenteses. After the intrapleural administra- There is no standard therapy for MPE. Various anti-mye- tion of bortezomib the patient became thoracocentesis-inde- loma agents in combination with local treatment approaches pendent, and in a two-week period the CT scan confirmed targeted at pleural effusion, for example, pleurodesis, were significant regression of pleural effusion (Figure 1(b)). Sub- tested without significant effect. High-dose chemotherapy sequently, the patient received four cycles of fourth-line with peripheral blood stem cell support for MPE did not con- therapy—PAD with lenalidomide (added to combination fer clear survival advantage [7]. The intrapleural administra- due to the progression of extramedullary disease) but still tion of α-interferon [8] or doxorubicin [9]has been tested with no effect on extramedullary tumors. Due to the progres- in an attempt to increase concentrations of the drugs in the sion of the disease and poor tolerance of previous therapy pleural cavity. The data concerning intrapleural administra- (hypotension after bortezomib, cytopenia) immediate high- tion of bortezomib remains scarce. Iannitto et al. published dose melphalan therapy with stem cell support was planned; a case report of intrapleurally administered bortezomib in however, the patient eventually succumbed in November a patient with refractory MM, in whom MPE occurred late 2010 due to infectious complications just before the start of in the course of the disease. Their patient first received two stem cell mobilization. The autopsy was not performed at the cycles of i.v. bortezomib, dexamethasone, and pegylated lipo- request of the family. somal doxorubicin without any impact on the formation of pleural effusion. Thus, the therapy was modified and in the third cycle half of the bortezomib dose was administered intrapleurally (for the total of 4 injections). After completion 3. Discussion of the single-modified cycle of bortezomib, MPE disappeared Multiple myeloma is the second most common hematologic [10]. Similarly, in our patient only as few as two intrapleural malignancy after non-Hodgkin’s lymphoma and is responsi- administrations of bortezomib (0.75 mg/m each) resulted in a rapid improvement of clinical symptoms, followed by a ble for 2% of cancer deaths [3]. The plasma cell disorder is characterized by the proliferation of malignant plasmocytes gradual disappearance of MPE. We assume that increased accumulating mainly in the bone marrow and by the pro- intrapleural concentration of bortezomib as a result of local duction of monoclonal immunoglobulin [4]. Apart from this administration might represent a major factor responsible characteristic features the clinical manifestations of disease for the rapid remission of MPE. In conclusion, intrapleural Case Reports in Immunology 3 administration of bortezomib appears safe and efficacious treatment approach targeted at MPE and MPE-related clini- cal symptoms. Conflict of Interests None of the authors of the paper has declared any conflict of interests. Acknowledgment This work is supported by Grant nos. IGA MZ CR NT12215- 4/2011, IGA MZ NS/10287-3, PRVOUK-P24/LF1/3, and GA- UK 44621. References [1] J. S. Kintzer, E. C. Rosenow, and R. A. Kyle, “Thoracic and pul- monary abnormalities in multiple myeloma. A review of 958 cases,” Archives of Internal Medicine, vol. 138, no. 5, pp. 727– 730, 1978. [2] Y.M.Kim,K.K.Lee,H.S.Ohetal., “Myelomatous effusion with poor response to chemotherapy,” Journal of Korean Medi- cal Science, vol. 15, no. 2, pp. 243–246, 2000. [3] R. A. Kyle and S. V. Rajkumar, “Multiple myeloma,” Blood, vol. 111, no. 6, pp. 2962–2972, 2008. [4] R. Bataille and J. L. Harousseau, “Multiple myeloma,” New England Journal of Medicine, vol. 336, no. 23, pp. 1657–1665, [5] J. N. Rodriguez, A. Pereira, J. C. Martinez, J. Conde, and E. Pujol, “Pleural effusion in multiple myeloma,” Chest, vol. 105, no. 2, pp. 622–624, 1994. [6] J. C. Hughes and M. L. Votaw, “Pleural effusion in multiple myeloma,” Cancer, vol. 44, no. 3, pp. 1150–1154, 1979. [7] R. Kamble, C. S. Wilson, A. Fassas et al., “Malignant pleural effusion of multiple myeloma: prognostic factors and out- come,” Leukemia and Lymphoma, vol. 46, no. 8, pp. 1137– 1142, 2005. [8] S. Makino, S. Yamahara, Y. Nagake, and J. Kamura, “Bence- Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy,” Internal Medicine, vol. 31, no. 5, pp. 617–621, 1992. [9] E. Iannitto, R. Scaglione, M. Musso, V. Abbadessa, and G. Licata, “Intrapleural adriamycin in treatment of myelomatous pleural effusion: a case report,” Haematologica, vol. 73, no. 4, pp. 325–326, 1988. [10] E. Iannitto, V. Minardi, and C. Tripodo, “Use of intrapleural bortezomib in myelomatous pleural effusion,” British Journal of Haematology, vol. 139, no. 4, pp. 621–622, 2007. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Immunology Hindawi Publishing Corporation

Intrapleural Bortezomib for the Therapy of Myelomatous Pleural Effusion: A Case Report

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Copyright © 2012 Magdalena Klanova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Publishing Corporation Case Reports in Immunology Volume 2012, Article ID 978479, 3 pages doi:10.1155/2012/978479 Case Report Intrapleural Bortezomib for the Therapy of Myelomatous Pleural Effusion: A Case Report 1, 2 1, 2 1, 3 1 1 Magdalena Klanova, Pavel Klener, Marek Trneny, Jan Straub, and Ivan Spicka 1st Department of Medicine and Clinical Department of Hematology, the General Teaching Hospital, Charles University in Prague, Prague, Czech Republic Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic Institute of Hematology and Blood Transfusion, Prague, Czech Republic Correspondence should be addressed to Ivan Spicka, spicka@cesnet.cz Received 18 August 2012; Accepted 20 September 2012 Academic Editors: N. Martinez-Quiles, H. Narimatsu, M. M. Nogueras, and H. L. Trivedi Copyright © 2012 Magdalena Klanova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Myelomatous pleural effusion (MPE) is an extremely rare manifestation of multiple myeloma (MM). We present a case of MPE in a patient with IgG-κ MM treated with intrapleural bortezomib with systemic bortezomib-based therapy. Although we observed good local response, the patient succumbed due to systemic myeloma progression. 1. Introduction right ovary, multiple osteolytic lesions in the skull and ribs, and bilateral axillar lymphadenopathy. Immunohistochem- Myelomatous pleural effusion is an extremely rare manifes- ical analysis of the breast tumor biopsy revealed plasmacy- tation of multiple myeloma and only a few cases have been toma/multiple myeloma. Bone marrow examination by tre- reported to date [1]. MPE in patients with MM is often phine biopsy revealed 30% infiltration with atypical plasma associated with high-risk disease and poor prognosis despite cells. Cytogenetic studies including FISH showed a dele- aggressive treatment. There is no standard treatment strategy tion of chromosome 13 and amplification of 1q21 and 1q26 for MPE and the majority of cases of MM presenting with genomic regions. On admission the total plasma protein MPE were associated with resistance to therapy [2]. Borte- was 106 g/L, albumin 40 g/L, urea 5.7 mmol/L, creatinine zomib (the dipeptidylboronic acid analogue, proteasome 74 umol/L, calcium 2.12 mmol/L, LDH 3.7 ukat/L (normal inhibitor) belongs now to backbone antimyeloma drugs. The values 2,2–3,75 ukat/L), and β-2 microglobulin 3.0 mg/L data concerning intrapleural administration of bortezomib is (normal values 1.0–2,4 mg/L). The international staging sys- scarce. We present a case of MPE in a patient with IgG-κ MM tem (ISS) score was 1. Serum protein electrophoresis with treated with intrapleural bortezomib and concomitantly with immunofixation confirmed monoclonal gammopathy IgG-κ systemic bortezomib-based-combined therapy. 44 g/L. Initially, the patient was treated with cyclophospha- mide, thalidomide, and dexamethasone (CTD), but achieved no objective response (stable disease). In the second line ther- 2. Case History apy bortezomib (Velcade) was added (VTD combination) A 43-year-old female initially presented to the hospital in but due to side effects (severe myopathy) dexamethasone had November 2009 with a dry cough, dyspnea, and left chest to be shortly discontinued. pain. The chest X-ray showed bilateral pneumonia. The com- In July 2010, after 2 VT cycles, the CT scan showed a puter tomography demonstrated a massive tumor involving progression of extranodal masses with massive left pleural the left breast and chest cavity, a tumor in the uterus and effusion (Figure 1(a)). The flow-cytometry analysis of pleural 2 Case Reports in Immunology (a) (b) Figure 1: (a) Chest X-ray of patient showing massive left pleural effusion and (b) reduction of the pleural effusion after two doses of intrapleural bortezomib. effusion demonstrated infiltration with atypical plasma cells could be variable. Pleural effusion is an untypical finding in thereby confirming the diagnosis of MPE. Repeated evacu- myeloma patients affecting approximately 6% of the cases ations of the pleural fluid resulted only in short alleviations [1]. The pathogenesis most frequently involves congestive followed by rapid replenishment of the MPE. The patient was heart failure due to amyloidosis and cardiac disease in the indicated to third-line therapy and received 1 modified cycle older myeloma population [5, 6]. MPE itself due to involve- of bortezomib, doxorubicin, and dexamethasone (PAD), in ment of the pleura is extremely rare and only a few cases have which, on days 8 and 11, one-half of the bortezomib dose been reported to date. Kintzer et al. reported 0.8% cases of (i.e., 0.75 mg/m ) was administered intrapleurally and the MPE from 958 patients with MM [1]. MPE usually occurs other half (i.e., 0.75 mg/m ) intravenously. The patient thus as a late complication of MM in the course of the disease received two doses of intrapleural bortezomib (0.75 mg/m ) progression and is associated with very poor prognosis. A three days apart, namely, in an attempt to mitigate the survival rate of less than 4 months has been reported in the symptoms associated with pleural effusion refractory to few cases of MPE despite aggressive treatment [6]. repeated thoracocenteses. After the intrapleural administra- There is no standard therapy for MPE. Various anti-mye- tion of bortezomib the patient became thoracocentesis-inde- loma agents in combination with local treatment approaches pendent, and in a two-week period the CT scan confirmed targeted at pleural effusion, for example, pleurodesis, were significant regression of pleural effusion (Figure 1(b)). Sub- tested without significant effect. High-dose chemotherapy sequently, the patient received four cycles of fourth-line with peripheral blood stem cell support for MPE did not con- therapy—PAD with lenalidomide (added to combination fer clear survival advantage [7]. The intrapleural administra- due to the progression of extramedullary disease) but still tion of α-interferon [8] or doxorubicin [9]has been tested with no effect on extramedullary tumors. Due to the progres- in an attempt to increase concentrations of the drugs in the sion of the disease and poor tolerance of previous therapy pleural cavity. The data concerning intrapleural administra- (hypotension after bortezomib, cytopenia) immediate high- tion of bortezomib remains scarce. Iannitto et al. published dose melphalan therapy with stem cell support was planned; a case report of intrapleurally administered bortezomib in however, the patient eventually succumbed in November a patient with refractory MM, in whom MPE occurred late 2010 due to infectious complications just before the start of in the course of the disease. Their patient first received two stem cell mobilization. The autopsy was not performed at the cycles of i.v. bortezomib, dexamethasone, and pegylated lipo- request of the family. somal doxorubicin without any impact on the formation of pleural effusion. Thus, the therapy was modified and in the third cycle half of the bortezomib dose was administered intrapleurally (for the total of 4 injections). After completion 3. Discussion of the single-modified cycle of bortezomib, MPE disappeared Multiple myeloma is the second most common hematologic [10]. Similarly, in our patient only as few as two intrapleural malignancy after non-Hodgkin’s lymphoma and is responsi- administrations of bortezomib (0.75 mg/m each) resulted in a rapid improvement of clinical symptoms, followed by a ble for 2% of cancer deaths [3]. The plasma cell disorder is characterized by the proliferation of malignant plasmocytes gradual disappearance of MPE. We assume that increased accumulating mainly in the bone marrow and by the pro- intrapleural concentration of bortezomib as a result of local duction of monoclonal immunoglobulin [4]. Apart from this administration might represent a major factor responsible characteristic features the clinical manifestations of disease for the rapid remission of MPE. In conclusion, intrapleural Case Reports in Immunology 3 administration of bortezomib appears safe and efficacious treatment approach targeted at MPE and MPE-related clini- cal symptoms. Conflict of Interests None of the authors of the paper has declared any conflict of interests. Acknowledgment This work is supported by Grant nos. IGA MZ CR NT12215- 4/2011, IGA MZ NS/10287-3, PRVOUK-P24/LF1/3, and GA- UK 44621. References [1] J. S. Kintzer, E. C. Rosenow, and R. A. Kyle, “Thoracic and pul- monary abnormalities in multiple myeloma. A review of 958 cases,” Archives of Internal Medicine, vol. 138, no. 5, pp. 727– 730, 1978. [2] Y.M.Kim,K.K.Lee,H.S.Ohetal., “Myelomatous effusion with poor response to chemotherapy,” Journal of Korean Medi- cal Science, vol. 15, no. 2, pp. 243–246, 2000. [3] R. A. Kyle and S. V. Rajkumar, “Multiple myeloma,” Blood, vol. 111, no. 6, pp. 2962–2972, 2008. [4] R. Bataille and J. L. Harousseau, “Multiple myeloma,” New England Journal of Medicine, vol. 336, no. 23, pp. 1657–1665, [5] J. N. Rodriguez, A. Pereira, J. C. Martinez, J. Conde, and E. Pujol, “Pleural effusion in multiple myeloma,” Chest, vol. 105, no. 2, pp. 622–624, 1994. [6] J. C. Hughes and M. L. Votaw, “Pleural effusion in multiple myeloma,” Cancer, vol. 44, no. 3, pp. 1150–1154, 1979. [7] R. Kamble, C. S. Wilson, A. Fassas et al., “Malignant pleural effusion of multiple myeloma: prognostic factors and out- come,” Leukemia and Lymphoma, vol. 46, no. 8, pp. 1137– 1142, 2005. [8] S. Makino, S. Yamahara, Y. Nagake, and J. Kamura, “Bence- Jones myeloma with pleural effusion: response to α-interferon and combined chemotherapy,” Internal Medicine, vol. 31, no. 5, pp. 617–621, 1992. [9] E. Iannitto, R. Scaglione, M. Musso, V. Abbadessa, and G. Licata, “Intrapleural adriamycin in treatment of myelomatous pleural effusion: a case report,” Haematologica, vol. 73, no. 4, pp. 325–326, 1988. [10] E. Iannitto, V. Minardi, and C. Tripodo, “Use of intrapleural bortezomib in myelomatous pleural effusion,” British Journal of Haematology, vol. 139, no. 4, pp. 621–622, 2007. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

Journal

Case Reports in ImmunologyHindawi Publishing Corporation

Published: Oct 11, 2012

References