A comparison of lenalidomide/dexamethasone versus cyclophosphamide/lenalidomide/dexamethasone versus cyclophosphamide/bortezomib/dexamethasone in newly diagnosed multiple myeloma

Meaghan L. Khan, Craig B. Reeder, Shaji K Kumar, Martha Lacy, Donna E. Reece, Angela Dispenzieri, Morie Gertz, Phillip Greipp, Suzanne Hayman, Steven Zeldenhurst, David M Dingli, John Lust, Stephen J Russell, Kristina M. Laumann, Joseph R Mikhael, Peter Leif Bergsagel, Rafael Fonseca, S Vincent Rajkumar, Alexander Keith Stewart

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Abstract

Novel agents are considered standard components of induction therapy for newly diagnosed patients with multiple myeloma. We retrospectively compared the results of three consecutive phase 2 clinical trials; RD (lenalidomide/dexamethasone, n=34), CRD (cyclophosphamide/lenalidomide/dexamethasone, n=53) and CyBorD (cyclophosphamide/bortezomib/dexamethasone, n=63) (N=150). Response rates after four cycles of treatment were: ≥near complete response (nCR), 12% vs. 2% vs. 41%, P<0·0001 and very good partial response or better, 35% vs. 30% vs. 65%, P=0·0003, respectively. With all cycles of therapy considered, ≥nCR was 35%, 15% and 41%, P=0·006. However, there is no evidence that one regimen produced superior progression-free survival (PFS) (median: 3·2 vs. 2·3 vs. 2·7years, P=0·11) or overall survival (3-year: 88% vs. 79% vs. 88%, P=0·23). Transplantation did not impact PFS (median: 2·7 vs. 2·3years, P=0·41) but was associated with improved OS (3-year: 93% vs. 75%, P≤0·001). High genetic risk patients (n=40) had earlier relapse despite lenalidomide or bortezomib (median: 2·1 vs. 2·7years, P=0·45). Grade 3/4 toxicities were least with CyBorD while CRD had most toxicity. In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80% of patients treated with modern therapeutic approaches are alive at 4 years.

Original languageEnglish (US)
Pages (from-to)326-333
Number of pages8
JournalBritish Journal of Haematology
Volume156
Issue number3
DOIs
StatePublished - Feb 2012

Fingerprint

Multiple Myeloma
Cyclophosphamide
Dexamethasone
Disease-Free Survival
Therapeutics
Transplantation
lenalidomide
Bortezomib
Clinical Trials
Recurrence
Survival

Keywords

  • Bortezomib
  • Cyclophosphamide
  • Lenalidomide
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "A comparison of lenalidomide/dexamethasone versus cyclophosphamide/lenalidomide/dexamethasone versus cyclophosphamide/bortezomib/dexamethasone in newly diagnosed multiple myeloma",
abstract = "Novel agents are considered standard components of induction therapy for newly diagnosed patients with multiple myeloma. We retrospectively compared the results of three consecutive phase 2 clinical trials; RD (lenalidomide/dexamethasone, n=34), CRD (cyclophosphamide/lenalidomide/dexamethasone, n=53) and CyBorD (cyclophosphamide/bortezomib/dexamethasone, n=63) (N=150). Response rates after four cycles of treatment were: ≥near complete response (nCR), 12{\%} vs. 2{\%} vs. 41{\%}, P<0·0001 and very good partial response or better, 35{\%} vs. 30{\%} vs. 65{\%}, P=0·0003, respectively. With all cycles of therapy considered, ≥nCR was 35{\%}, 15{\%} and 41{\%}, P=0·006. However, there is no evidence that one regimen produced superior progression-free survival (PFS) (median: 3·2 vs. 2·3 vs. 2·7years, P=0·11) or overall survival (3-year: 88{\%} vs. 79{\%} vs. 88{\%}, P=0·23). Transplantation did not impact PFS (median: 2·7 vs. 2·3years, P=0·41) but was associated with improved OS (3-year: 93{\%} vs. 75{\%}, P≤0·001). High genetic risk patients (n=40) had earlier relapse despite lenalidomide or bortezomib (median: 2·1 vs. 2·7years, P=0·45). Grade 3/4 toxicities were least with CyBorD while CRD had most toxicity. In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80{\%} of patients treated with modern therapeutic approaches are alive at 4 years.",
keywords = "Bortezomib, Cyclophosphamide, Lenalidomide, Multiple myeloma",
author = "Khan, {Meaghan L.} and Reeder, {Craig B.} and Kumar, {Shaji K} and Martha Lacy and Reece, {Donna E.} and Angela Dispenzieri and Morie Gertz and Phillip Greipp and Suzanne Hayman and Steven Zeldenhurst and Dingli, {David M} and John Lust and Russell, {Stephen J} and Laumann, {Kristina M.} and Mikhael, {Joseph R} and Bergsagel, {Peter Leif} and Rafael Fonseca and Rajkumar, {S Vincent} and Stewart, {Alexander Keith}",
year = "2012",
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T1 - A comparison of lenalidomide/dexamethasone versus cyclophosphamide/lenalidomide/dexamethasone versus cyclophosphamide/bortezomib/dexamethasone in newly diagnosed multiple myeloma

AU - Khan, Meaghan L.

AU - Reeder, Craig B.

AU - Kumar, Shaji K

AU - Lacy, Martha

AU - Reece, Donna E.

AU - Dispenzieri, Angela

AU - Gertz, Morie

AU - Greipp, Phillip

AU - Hayman, Suzanne

AU - Zeldenhurst, Steven

AU - Dingli, David M

AU - Lust, John

AU - Russell, Stephen J

AU - Laumann, Kristina M.

AU - Mikhael, Joseph R

AU - Bergsagel, Peter Leif

AU - Fonseca, Rafael

AU - Rajkumar, S Vincent

AU - Stewart, Alexander Keith

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N2 - Novel agents are considered standard components of induction therapy for newly diagnosed patients with multiple myeloma. We retrospectively compared the results of three consecutive phase 2 clinical trials; RD (lenalidomide/dexamethasone, n=34), CRD (cyclophosphamide/lenalidomide/dexamethasone, n=53) and CyBorD (cyclophosphamide/bortezomib/dexamethasone, n=63) (N=150). Response rates after four cycles of treatment were: ≥near complete response (nCR), 12% vs. 2% vs. 41%, P<0·0001 and very good partial response or better, 35% vs. 30% vs. 65%, P=0·0003, respectively. With all cycles of therapy considered, ≥nCR was 35%, 15% and 41%, P=0·006. However, there is no evidence that one regimen produced superior progression-free survival (PFS) (median: 3·2 vs. 2·3 vs. 2·7years, P=0·11) or overall survival (3-year: 88% vs. 79% vs. 88%, P=0·23). Transplantation did not impact PFS (median: 2·7 vs. 2·3years, P=0·41) but was associated with improved OS (3-year: 93% vs. 75%, P≤0·001). High genetic risk patients (n=40) had earlier relapse despite lenalidomide or bortezomib (median: 2·1 vs. 2·7years, P=0·45). Grade 3/4 toxicities were least with CyBorD while CRD had most toxicity. In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80% of patients treated with modern therapeutic approaches are alive at 4 years.

AB - Novel agents are considered standard components of induction therapy for newly diagnosed patients with multiple myeloma. We retrospectively compared the results of three consecutive phase 2 clinical trials; RD (lenalidomide/dexamethasone, n=34), CRD (cyclophosphamide/lenalidomide/dexamethasone, n=53) and CyBorD (cyclophosphamide/bortezomib/dexamethasone, n=63) (N=150). Response rates after four cycles of treatment were: ≥near complete response (nCR), 12% vs. 2% vs. 41%, P<0·0001 and very good partial response or better, 35% vs. 30% vs. 65%, P=0·0003, respectively. With all cycles of therapy considered, ≥nCR was 35%, 15% and 41%, P=0·006. However, there is no evidence that one regimen produced superior progression-free survival (PFS) (median: 3·2 vs. 2·3 vs. 2·7years, P=0·11) or overall survival (3-year: 88% vs. 79% vs. 88%, P=0·23). Transplantation did not impact PFS (median: 2·7 vs. 2·3years, P=0·41) but was associated with improved OS (3-year: 93% vs. 75%, P≤0·001). High genetic risk patients (n=40) had earlier relapse despite lenalidomide or bortezomib (median: 2·1 vs. 2·7years, P=0·45). Grade 3/4 toxicities were least with CyBorD while CRD had most toxicity. In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80% of patients treated with modern therapeutic approaches are alive at 4 years.

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