Abstract
Background
This was an open-label, observational, prospective assessment. We conducted an analysis of the impact of bortezomib-based therapy (PAD: bortezomib, doxorubicin, high-dose dexamethasone vs. CBd: cyclophosphamide bortezomib, low-dose dexamethasone) on the survival rates and adverse events in elderly patients with newly diagnosed multiple myeloma (MM).
Methods
Out of 303 patients, 128 received the PAD regimen and the other 175 patients received the CBd induction therapy (age 65–89 years). Baseline patient characteristics between the two cohorts were balanced in age (P = 0.69), international staging system (ISS) prognostic stages (P = 0.90), serum calcium (P = 0.70), and serum creatinine (P = 0.52).
Results
Overall response (OS) after the induction chemotherapy was achieved in 214 of 303 patients (70.6 %), with no significant differences observed between the two treatment groups (71.9 vs. 69.7 %, P = 0.68). Patients with ISS stage 2 reached the same 5-year OS advantages compared to patients with ISS stage 1, because they received bortezomib-based PAD or CBd treatments. Patients receiving CBd protocol gained similar satisfactory progression-free survival (PFS) results when compared to the PAD regimen group: PFS at 5 years reached 58.2 versus 58.9 % (P = 0.85). Five-year OS in the CBd arm had significant advantages compared to the PAD group, 79.9 versus 49.9 % (P < 0.05). The overall safety profiles showed that 26 of 128 (20.3 %) patients died in the PAD arm, while 13 of 175 patients died (7.4 %) in the CBd group (P < 0.01). Similarly, the PAD arm had a higher serious infection rate than that of the CBd arm (39.2 vs. 13.1 %, P < 0.01).
Conclusions
Bortezomib benefits elderly patients with newly diagnosed MM; they achieve satisfactory treatment responses and survival advantages. Further, patients treated with CBd have superior treatment advantages, with a predictable safety profile, when compared to the PAD regimen.
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References
Anagnostopoulos A, Gika D, Symeonidis A, Zervas K, Pouli A, Repoussis P et al (2005) Multiple myeloma in elderly patients: prognostic factors and outcome. Eur J Haematol 75:370–375
Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G et al (1998) 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 102:1115–1123
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J et al (2005) International staging system for multiple myeloma. J Clin Oncol 23:3412–3420
Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M et al (2010) 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 28:4621–4629
Huang BT, Zeng QC, Yu J, Xiao Z, Li BS, Zhang CL et al (2012a) How to determine post-RCHOP therapy for risk-tailored adult patients with diffuse large B-cell lymphoma, addition of maintenance rituximab or observation: multicenter experience. J Cancer Res Clin Oncol 138:125–132
Huang BT, Zeng QC, Yu J, Liu XL, Xiao Z, Zhu HQ (2012b) High-dose homoharringtonine versus standard-dose daunorubicin is effective and safe as induction and post-induction chemotherapy for elderly patients with acute myeloid leukemia: a multicenter experience from China. Med Oncol 29:251–259
International Myeloma Working Group (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121(5):749–757
Kane RC, Farrell AT, Sridhara R, Pazdur R (2006) United States food and drug administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin Cancer Res 12:2955–2960
Kastritis E, Zervas K, Symeonidis A, Terpos E, Delimbassi S, Anagnostopoulos N et al (2009) Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the international staging system (ISS): an analysis of the Greek myeloma study group (GMSG). Leukemia 23:1152–1157
Ludwig H, Viterbo L, Greil R, Masszi T, Spicka I, Shpilberg O et al (2013) Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma. J Clin Oncol 31:247–255
Palumbo A, Mateos MV, Bringhen S, San Miguel JF (2011) Practical management of adverse events in multiple myeloma: can therapy be attenuated in older patients? Blood Rev 25:181–191
Rajkumar SV, Buadi F (2007) Multiple myeloma: new staging systems for diagnosis, prognosis and response evaluation. Best Pract Res Clin Haematol 20:665–680
Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H et al (2012) Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol 30:2946–2955
Stewart AK, Bergsagel PL, Greipp PR, Dispenzieri A, Gertz MA, Hayman SR et al (2007) A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy. Leukemia 21:529–534
Tan D, Teoh G, Lau LC, Lim A, Lim TH, Yap KC et al (2010) An abnormal nonhyperdiploid karyotype is a significant adverse prognostic factor for multiple myeloma in the bortezomib era. Am J Hematol 85:752–756
Yang GZ, Chen WM (2010) Bortezomib-based regimen for the treatment of 110 multiple myeloma patients. Zhonghua Yi Xue Za Zhi 90:2671–2674
Zhao Y, Dou LP, Wang SH, Bo J, Wang QS, Huang WR et al (2010) The efficacy and safety of PAD and VAD regimens for untreated multiple myeloma. Zhonghua Nei Ke Za Zhi 49:762–764
Acknowledgments
We would like to thank all the patients and the clinicians from the participating sites. This work was supported by grants from the Natural Science Foundation of Inner Mongolia (2013MS1157). All authors discussed the results and commented on the manuscript.
Conflict of interest
I would like to declare on behalf of my co-authors that this work is original research that has not been published previously and is not under consideration for publication elsewhere either in part of in whole. All the authors listed have approved the manuscript that is enclosed.
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Bin-Tao Huang and Yan Tan have contributed equally to this work.
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Huang, BT., Tan, Y., Zhao, WH. et al. How to determine bortezomib-based regimen for elderly patients with multiple myeloma: PAD versus CBd, an observational study. J Cancer Res Clin Oncol 140, 303–309 (2014). https://doi.org/10.1007/s00432-013-1570-6
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DOI: https://doi.org/10.1007/s00432-013-1570-6