Abstract
Background/Aims: The incorporation of bortezomib into the chemotherapeutic regimens for non-transplant patients with multiple myeloma resulted in improved outcomes in controlled studies. This prospective, non-interventional study assessed the effectiveness and safety of bortezomib-containing regimens in daily practice. Methods: Patients with untreated or relapsed multiple myeloma not eligible for high-dose chemotherapy followed by autologous stem cell transplantation and who were scheduled for bortezomib mono- or combination therapy or melphalan-prednisone (MP) alone were included in this study. Dosage and treatment decisions were at the discretion of the physicians. Results: 353 patients received bortezomib-containing therapies and 37 patients MP alone. Overall response rates at treatment end were 65.9% for bortezomib-containing therapies and 50.0% for MP. Partial or complete remissions considered best responses were achieved in 82.6% (first line) and 63.8% (second or later line) of the bortezomib-treated patients. The median duration of response to bortezomib-containing therapies was 18.2 months in 109 first-line and 11.3 months in 110 second- or later-line patients. Adverse drug reactions of any grade were reported during the treatment phase in 79.6% (bortezomib) and 70.3% (MP) of treated patients. Conclusion: Bortezomib-containing therapies were effective in patients with multiple myeloma in a real-life setting. The increasingly individualized treatment regimens of multiple myeloma require standardized assessments of response in daily practice.
Journal Section:
Original Article
References
1.
Ferlay J, Shin H, Bray F, et al.: GLOBOCAN 2008 (version 1.2), Cancer Incidence and Mortality Worldwide. Lyon, France: International Agency for Research on Cancer, 2010.
2.
Onkopedia Leitlinie. Multiples Myelom. DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V. (ed), Berlin, DGHO, 2013.
3.
Kaatsch P, Spix C, Katalinic A, Hentschel S: Krebs in Deutschland 2007/2008 (Cancer in Germany 2007/2008); Eine gemeinsame Veröffentlichung des Robert Koch-Instituts und der Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. Berlin, Robert Koch-Institut, 2012.
4.
Engelhardt M, Terpos E, Kleber M, et al.: European Myeloma network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica 2014;99:232-242.
[PubMed]
5.
Facon T, Dimopoulos MA, Dispenzieri A, et al.: Initial phase 3 results of the first (frontline investigation of lenalidomide + dexamethasone versus standard thalidomide) trial (MM-020/IFM 0701) in newly diagnosed multiple myeloma (NDMM) patients (Pts) ineligible for stem cell transplantation (SCT). Blood 2013;122:2(abstract).
6.
Kumar SK, Rajkumar SV, Dispenzieri A, et al.: Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111:2516-2520.
[PubMed]
7.
Kumatori A, Tanaka K, Inamura N, et al.: Abnormally high expression of proteasomes in human leukemic cells. Proc Natl Acad Sci USA 1990;87:7071-7075.
[PubMed]
8.
Richardson PG, Sonneveld P, Schuster MW, et al.: Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;352:2487-2498.
[PubMed]
9.
San Miguel JF, Schlag R, Khuageva NK, et al.: Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906-917.
[PubMed]
10.
Harousseau JL, Attal M, Avet-Loiseau H, et al.: Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: Results of the IFM 2005-01 phase III trial. J Clin Oncol 2010;28:4621-4629.
[PubMed]
11.
Rosiñol L, Oriol A, Teruel AI, et al.: Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: A randomized phase 3 PETHEMA/GEM study. Blood 2012;120:1589-1596.
[PubMed]
12.
Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998;102:1115-1123.
[PubMed]
13.
Durie BGM, Salmon SE: A clinical staging system for multiple myeloma: Correlation of measured myeloma cell mass with presenting clinical features, response to treatment and survival. Cancer 1975;36:842-854.
[PubMed]
14.
Mateos MV, Hernandez JM, Hernandez MT, et al.: Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: Results of a multicenter phase 1/2 study. Blood 2006;108:2165-2172.
[PubMed]
15.
Facon T, Mary JY, Hulin C, et al.: Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): A randomised trial. Lancet 2007;370:1209-1218.
[PubMed]
16.
Bird JM, Owen RG, D'Sa S, et al.: Haemato-oncology Task Force of British Committee for Standards in Haematology (BCSH) and UK Myeloma Forum: Guidelines for the diagnosis and management of multiple myeloma 2011. Br J Haematol 2011;154:32-75.
[PubMed]
17.
Jagannath S, Barlogie B, Berenson JR, et al.: Bortezomib in recurrent and/or refractory multiple myeloma. Initial clinical experience in patients with impaired renal function. Cancer 2005;103:1195-1200.
[PubMed]
18.
Dimopoulos MA, Richardson PG, Schlag R, et al.: VMP (bortezomib, melphalan, and prednisone) is active and well tolerated in newly diagnosed patients with multiple myeloma with moderately impairs renal function, and results in reversal of renal impairment: Cohort analysis of the phase III VISTA study. J Clin Oncol 2009;27:6086-6093.
[PubMed]
19.
Scheid C, Sonneveld P, Schmidt-Wolf IG, et al.: Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma: a subgroup analysis from the HOVON-65/GMMG-HD4 trial. Haematologica 2014;99:148-154.
[PubMed]
20.
Mateos MV, Richardson PG, Shi H, et al.: Higher cumulative bortezomib dose results in better overall survival (OS) in patients with previously untreated multiple myeloma (MM) receiving bortezomib-melphalan-prednisone (VMP) in the phase 3 VISTA study. Blood 2013;122:1968(abstract).
21.
Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: A randomized, phase 3, non-inferiority study. Lancet Oncol 2011;12:431-440.
[PubMed]
22.
Palumbo A, Bringhen S, Caravita T, et al.: Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: Randomized controlled trial. Lancet 2006;367:825-831.
[PubMed]
23.
Leiper JM, Lawson DH: Why do doctors not report adverse drug reactions?. Neth J Med 1985;28:546-550.
[PubMed]
24.
Bringhen S, Larocca A, Rossi D, et al.: Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 2010;116:4745-4753.
[PubMed]
25.
Fukushima T, Nakamura T, Iwao H, et al.: Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: Once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Anticancer Res 2011;31:2297-2302.
[PubMed]
26.
Mateos MV, Bringhen S, Richardson PG, et al.: Bortezomib cumulative dose, efficacy, and tolerability with three different bortezomib-melphalan-prednisone regimens in previously untreated myeloma patients ineligible for high-dose therapy. Haematologica 2014;99:1114-1122.
[PubMed]
27.
Kropff M, Bisping G, Schuck E, et al.: Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol 2007;138:330-337.
[PubMed]
28.
Tong Y, Qian J, Li Y, Meng H, Jin J: The high incidence of varicella herpes zoster with the use of bortezomib in 10 patients. Am J Hematol 2007;82:403-404.
[PubMed]
29.
Chanan-Khan A, Sonneveld P, Schuster MW, et al.: Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study. J Clin Oncol 2008;26:4784-4790.
[PubMed]
30.
Vickrey E, Allen S, Mehta J, Singhal S: Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy. Cancer 2009;115:229-232.
[PubMed]
31.
Swaika A, Paulus A, Miller KC, et al.: Acyclovir prophylaxis against varicella zoster virus reactivation in multiple myeloma patients treated with bortezomib-based therapies: A retrospective analysis of 100 patients. J Support Oncol 2012;10:155-159.
[PubMed]
© 2015 S. Karger GmbH, Freiburg
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2015
You do not currently have access to this content.
