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Erschienen in: Indian Journal of Hematology and Blood Transfusion 1/2017

27.01.2016 | Original Article

Once-Weekly 1.6 mg/m2 Bortezomib BCD Regimen in Elderly Patients with Newly Diagnosed Multiple Myeloma Who are Unfit for Standard Dose Chemotherapy

verfasst von: Yong Tang, Ye-hua Yu, Yi-yun Yao, Li-fang Zou, Hong-ju Dou, Lei Wang, Qi Zhu

Erschienen in: Indian Journal of Hematology and Blood Transfusion | Ausgabe 1/2017

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Abstract

Bortezomib has shown anti-myeloma effects in combination with alkylating agents, but clinical benefits can be limited by neurotoxicity. There is less information on the efficacy and tolerability of once-weekly 1.6 mg/m2 bortezomib combined with cyclophosphamide and dexamethasone (BCD) regimen in elderly patients with newly diagnosed multiple myeloma who are unfit for standard dose chemotherapy. Here, we report our experience of weekly 1.6 mg/m2 intravenous bortezomib in this group of patients. Between March 2010 and February 2015, we treated 34 newly diagnosed elderly patients with the combination of bortezomib 1.6 mg/m2 intravenously on days 1 and 8; cyclophosphamide 200 mg/m2 intravenously on days 1–4; dexamethasone 20 mg intravenously on days 1–4, and 8–11. Among the 34 patients, 14 (41 %) responded with complete response (CR), 6 (18 %) with very good partial response (VGPR) and 10 (29 %) with partial response (PR). The overall response rates were 88 %. After 2 cycles of treatments, the survival of patients who attained a response of VGPR or CR was significantly longer than those with PR or resistance to BCD, for both progression-free survival (PFS) (21.4 vs. 10.6 months, p = 0.002) and overall survival (OS) (23.0 vs. 16.8 months, p = 0.043). The 2-year PFS and OS were 26.5 and 64.7 % respectively in these elderly multiple myeloma patients in our study. Grade 1/2 neuropathy was observed in 20 % of the cycles while grade 3/4 neuropathy was not observed. No patients withdrew due to neuropathy or other side effects. Once-weekly bortezomib at 1.6 mg/m2 BCD regimen is both effective and safe in elderly patients with newly diagnosed multiple myeloma who are unfit for standard dose chemotherapy.
Literatur
2.
Zurück zum Zitat Rajkumar SV, Jacobus S, Callander NS et al (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11(1):29–37CrossRefPubMed Rajkumar SV, Jacobus S, Callander NS et al (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11(1):29–37CrossRefPubMed
3.
Zurück zum Zitat Rajkumar SV, Rosinol L, Hussein M et al (2008) Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 26(13):2171–2177CrossRefPubMedPubMedCentral Rajkumar SV, Rosinol L, Hussein M et al (2008) Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 26(13):2171–2177CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Mateos MV, Richardson PG, Schlag R et al (2010) Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol 28(13):2259–2266CrossRefPubMed Mateos MV, Richardson PG, Schlag R et al (2010) Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol 28(13):2259–2266CrossRefPubMed
5.
Zurück zum Zitat Vincent RS (2014) Multiple myeloma: 2014 Update on diagnosis, risk-stratification, and management. Am J Hematol 89(10):999–1009 Vincent RS (2014) Multiple myeloma: 2014 Update on diagnosis, risk-stratification, and management. Am J Hematol 89(10):999–1009
6.
Zurück zum Zitat Kim K, Lee JH, Kim JS et al (2014) Clinical profiles of multiple myeloma in Asia—an Asian Myeloma Network study. Am J Hematol 89(7):751–756CrossRefPubMed Kim K, Lee JH, Kim JS et al (2014) Clinical profiles of multiple myeloma in Asia—an Asian Myeloma Network study. Am J Hematol 89(7):751–756CrossRefPubMed
7.
Zurück zum Zitat Schaapveld M, Visser O, Siesling S, Schaar CG, Zweegman S, Vellenga E (2010) Improved survival among younger but not among older patients with Multiple Myeloma in the Netherlands, a population-based study since 1989. Eur J Cancer 46(1):160–169CrossRefPubMed Schaapveld M, Visser O, Siesling S, Schaar CG, Zweegman S, Vellenga E (2010) Improved survival among younger but not among older patients with Multiple Myeloma in the Netherlands, a population-based study since 1989. Eur J Cancer 46(1):160–169CrossRefPubMed
8.
9.
Zurück zum Zitat Kristinsson SY, Anderson WF, Landgren O (2014) Improved long-term survival in multiple myeloma up to the age of 80 years. Leukemia 28(6):1346–1348CrossRefPubMed Kristinsson SY, Anderson WF, Landgren O (2014) Improved long-term survival in multiple myeloma up to the age of 80 years. Leukemia 28(6):1346–1348CrossRefPubMed
10.
Zurück zum Zitat Palumbo A, Rajkumar SV, San MJF et al (2014) International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 32(6):587–600CrossRefPubMedPubMedCentral Palumbo A, Rajkumar SV, San MJF et al (2014) International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 32(6):587–600CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Palumbo A, Bringhen S, Mateos MV et al (2015) Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 125(13):2068–2074CrossRefPubMedPubMedCentral Palumbo A, Bringhen S, Mateos MV et al (2015) Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 125(13):2068–2074CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Palumbo A, Bringhen S, Ludwig H et al (2011) Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood 118(17):4519–4529CrossRefPubMed Palumbo A, Bringhen S, Ludwig H et al (2011) Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood 118(17):4519–4529CrossRefPubMed
13.
Zurück zum Zitat Bringhen S, Mateos MV, Zweegman S et al (2013) Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica 98(6):980–987CrossRefPubMedPubMedCentral Bringhen S, Mateos MV, Zweegman S et al (2013) Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica 98(6):980–987CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Moreau P, Pylypenko H, Grosicki S et al (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 12(5):431–440CrossRefPubMed Moreau P, Pylypenko H, Grosicki S et al (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 12(5):431–440CrossRefPubMed
15.
Zurück zum Zitat Moore S, Atwal S, Sachchithanantham S et al (2013) Weekly intravenous bortezomib is effective and well tolerated in relapsed/refractory myeloma. Eur J Haematol 90(5):420–425CrossRefPubMed Moore S, Atwal S, Sachchithanantham S et al (2013) Weekly intravenous bortezomib is effective and well tolerated in relapsed/refractory myeloma. Eur J Haematol 90(5):420–425CrossRefPubMed
16.
Zurück zum Zitat Reece DE, Hegenbart U, Sanchorawala V et al (2011) Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood 118(4):865–873CrossRefPubMed Reece DE, Hegenbart U, Sanchorawala V et al (2011) Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood 118(4):865–873CrossRefPubMed
17.
Zurück zum Zitat Mateos MV, Oriol A, Martinez-Lopez J et al (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 11(10):934–941CrossRefPubMed Mateos MV, Oriol A, Martinez-Lopez J et al (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 11(10):934–941CrossRefPubMed
18.
Zurück zum Zitat Reeder CB, Reece DE, Kukreti V et al (2009) Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 23(7):1337–1341CrossRefPubMedPubMedCentral Reeder CB, Reece DE, Kukreti V et al (2009) Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 23(7):1337–1341CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Ludwig H, Viterbo L, Greil R 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(2):247–255CrossRefPubMed Ludwig H, Viterbo L, Greil R 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(2):247–255CrossRefPubMed
20.
Zurück zum Zitat Kyle RA, Rajkumar SV (2009) Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 23(1):3–9CrossRefPubMed Kyle RA, Rajkumar SV (2009) Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 23(1):3–9CrossRefPubMed
21.
Zurück zum Zitat Greipp PR, San MJ, Durie BG et al (2005) International staging system for multiple myeloma. J Clin Oncol 23(15):3412–3420CrossRefPubMed Greipp PR, San MJ, Durie BG et al (2005) International staging system for multiple myeloma. J Clin Oncol 23(15):3412–3420CrossRefPubMed
22.
23.
Zurück zum Zitat Sopena M, Clavero EM, Villa P, Martinez-Lopez J (2012) Efficacy and safety of reduced-intensity induction therapy with a bortezomib-based regimen in elderly patients with multiple myeloma. Ther Adv Hematol 3(3):147–154CrossRefPubMedPubMedCentral Sopena M, Clavero EM, Villa P, Martinez-Lopez J (2012) Efficacy and safety of reduced-intensity induction therapy with a bortezomib-based regimen in elderly patients with multiple myeloma. Ther Adv Hematol 3(3):147–154CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Kumar S, Flinn I, Richardson PG et al (2012) Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 119(19):4375–4382CrossRefPubMed Kumar S, Flinn I, Richardson PG et al (2012) Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 119(19):4375–4382CrossRefPubMed
25.
Zurück zum Zitat Huang BT, Tan Y, Zhao WH, Zeng QC, Li BS, Chen RL (2014) How to determine bortezomib-based regimen for elderly patients with multiple myeloma: PAD versus CBd, an observational study. J Cancer Res Clin Oncol 140(2):303–309CrossRefPubMed Huang BT, Tan Y, Zhao WH, Zeng QC, Li BS, Chen RL (2014) How to determine bortezomib-based regimen for elderly patients with multiple myeloma: PAD versus CBd, an observational study. J Cancer Res Clin Oncol 140(2):303–309CrossRefPubMed
26.
Zurück zum Zitat Reeder CB, Reece DE, Kukreti V et al (2010) Once-versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood 115(16):3416–3417CrossRefPubMed Reeder CB, Reece DE, Kukreti V et al (2010) Once-versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood 115(16):3416–3417CrossRefPubMed
27.
Zurück zum Zitat van de Velde HJ, Liu X, Chen G, Cakana A, Deraedt W, Bayssas M (2007) Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica 92(10):1399–1406CrossRefPubMed van de Velde HJ, Liu X, Chen G, Cakana A, Deraedt W, Bayssas M (2007) Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica 92(10):1399–1406CrossRefPubMed
28.
Zurück zum Zitat Gay F, Larocca A, Wijermans P et al (2011) Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood 117(11):3025–3031CrossRefPubMed Gay F, Larocca A, Wijermans P et al (2011) Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood 117(11):3025–3031CrossRefPubMed
29.
Zurück zum Zitat Palumbo A, Mina R (2013) Management of older adults with multiple myeloma. Blood Rev 27(3):133–142CrossRefPubMed Palumbo A, Mina R (2013) Management of older adults with multiple myeloma. Blood Rev 27(3):133–142CrossRefPubMed
30.
Zurück zum Zitat Girnius SK, Lee S, Kambhampati S et al (2015) A phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation. Br J Haematol 169(1):36–43CrossRefPubMed Girnius SK, Lee S, Kambhampati S et al (2015) A phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation. Br J Haematol 169(1):36–43CrossRefPubMed
31.
Zurück zum Zitat Ong SY, Ng HY, Surendran S et al (2014) Subcutaneous bortezomib combined with weekly cyclophosphamide and dexamethasone is an efficient and well tolerated regime in newly diagnosed multiple myeloma. Br J Haematol 169(5):754–756CrossRefPubMed Ong SY, Ng HY, Surendran S et al (2014) Subcutaneous bortezomib combined with weekly cyclophosphamide and dexamethasone is an efficient and well tolerated regime in newly diagnosed multiple myeloma. Br J Haematol 169(5):754–756CrossRefPubMed
32.
Zurück zum Zitat Dimopoulos MA, Roussou M, Gkotzamanidou M et al (2013) The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia 27(2):423–429CrossRefPubMed Dimopoulos MA, Roussou M, Gkotzamanidou M et al (2013) The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia 27(2):423–429CrossRefPubMed
Metadaten
Titel
Once-Weekly 1.6 mg/m2 Bortezomib BCD Regimen in Elderly Patients with Newly Diagnosed Multiple Myeloma Who are Unfit for Standard Dose Chemotherapy
verfasst von
Yong Tang
Ye-hua Yu
Yi-yun Yao
Li-fang Zou
Hong-ju Dou
Lei Wang
Qi Zhu
Publikationsdatum
27.01.2016
Verlag
Springer India
Erschienen in
Indian Journal of Hematology and Blood Transfusion / Ausgabe 1/2017
Print ISSN: 0971-4502
Elektronische ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-016-0647-1

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