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Long-term follow-up of MRC Myeloma IX Trial: survival outcomes with bisphosphonate and thalidomide treatment

Long-term follow-up of MRC Myeloma IX Trial: survival outcomes with bisphosphonate and thalidomide treatment
Long-term follow-up of MRC Myeloma IX Trial: survival outcomes with bisphosphonate and thalidomide treatment
Purpose: MRC Myeloma IX was a phase III trial evaluating bisphosphonate and thalidomide-based therapy for newly diagnosed multiple myeloma. Results were reported previously after a median follow-up of 3.7 years (Current Controlled Trials number: ISRCTN68454111). Survival outcomes were re-analyzed after an extended follow-up (median: 5.9 years).

Experimental design: At first randomization, patients (N = 1,970) were assigned to bisphosphonate (clodronic acid or zoledronic acid) and induction therapies (cyclophosphamide-vincristine-doxorubicin-dexamethasone [CVAD] or cyclophosphamide-thalidomide-dexamethasone [CTD] followed by high-dose therapy plus autologous stem cell transplantation for younger/fitter patients [intensive pathway], and melphalan-prednisone (MP) or attenuated CTD [CTDa] for older/less fit patients [non-intensive pathway]). At second randomization, patients were assigned to thalidomide maintenance therapy or no maintenance. Interphase FISH (iFISH) was used to analyze cytogenics.

Results: Zoledronic acid significantly improved progression-free survival (PFS; hazard ratio [HR], 0.89; P = 0.02) and overall survival (OS; HR, 0.86; P = 0.01) compared with clodronic acid. In the intensive pathway, CTD demonstrated non-inferior PFS and OS compared with CVAD, with a trend toward improved OS in patients with favorable cytogenics (P = 0.068). In the non-intensive pathway, CTDa significantly improved PFS (HR, 0.81; P = 0.007) compared with MP and there was an emergent survival benefit after 18-24 months. Thalidomide maintenance improved PFS (HR, 1.44; P < 0.0001) but not OS (HR, 0.96; P = 0.70), and was associated with shorter OS in patients with adverse cytogenics (P = 0.01).

Conclusions: Long-term follow-up is essential to identify clinically meaningful treatment effects in myeloma subgroups based on cytogenetics.
bisphosphonate, clodronic acid, zoledronic acid, multiple myeloma, cyclophosphamide-thalidomide-dexamethasone (CTD)
1078-0432
6030-6038
Morgan, Gareth J.
d285dcf8-ac2c-4fe0-acf9-4787eb025939
Davies, Faith E.
9ea9e143-ac51-431b-8cb5-57b8dc0a38af
Gregory, Walter M.
4a7a4c5a-0a88-4ba2-8f08-0c035dd0b6db
Bell, Susan E.
dd856494-5937-4c59-b922-7ea95e8600cf
Szubert, Alexander J.
f83d6436-08ec-46ea-878a-14fa54b27dc0
Cook, Gordon
4fe17be9-5e4e-4a58-a09a-b76f07f410f4
Drayson, Mark T.
282a00f4-8edf-4075-a83c-272ffcce53e8
Owen, Roger G.
5846329e-f7a0-44d9-ac7a-717fb76ff9b5
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Jackson, Graham H.
82e8cc2d-7530-4b02-8f92-176f47451839
Child, J. Anthony
1a7a739b-5295-4818-a455-3c67d9020abc
Morgan, Gareth J.
d285dcf8-ac2c-4fe0-acf9-4787eb025939
Davies, Faith E.
9ea9e143-ac51-431b-8cb5-57b8dc0a38af
Gregory, Walter M.
4a7a4c5a-0a88-4ba2-8f08-0c035dd0b6db
Bell, Susan E.
dd856494-5937-4c59-b922-7ea95e8600cf
Szubert, Alexander J.
f83d6436-08ec-46ea-878a-14fa54b27dc0
Cook, Gordon
4fe17be9-5e4e-4a58-a09a-b76f07f410f4
Drayson, Mark T.
282a00f4-8edf-4075-a83c-272ffcce53e8
Owen, Roger G.
5846329e-f7a0-44d9-ac7a-717fb76ff9b5
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Jackson, Graham H.
82e8cc2d-7530-4b02-8f92-176f47451839
Child, J. Anthony
1a7a739b-5295-4818-a455-3c67d9020abc

Morgan, Gareth J., Davies, Faith E., Gregory, Walter M., Bell, Susan E., Szubert, Alexander J., Cook, Gordon, Drayson, Mark T., Owen, Roger G., Ross, Fiona M., Jackson, Graham H. and Child, J. Anthony (2013) Long-term follow-up of MRC Myeloma IX Trial: survival outcomes with bisphosphonate and thalidomide treatment. Clinical Cancer Research, 19 (21), 6030-6038. (doi:10.1158/1078-0432.CCR-12-3211). (PMID:23995858)

Record type: Article

Abstract

Purpose: MRC Myeloma IX was a phase III trial evaluating bisphosphonate and thalidomide-based therapy for newly diagnosed multiple myeloma. Results were reported previously after a median follow-up of 3.7 years (Current Controlled Trials number: ISRCTN68454111). Survival outcomes were re-analyzed after an extended follow-up (median: 5.9 years).

Experimental design: At first randomization, patients (N = 1,970) were assigned to bisphosphonate (clodronic acid or zoledronic acid) and induction therapies (cyclophosphamide-vincristine-doxorubicin-dexamethasone [CVAD] or cyclophosphamide-thalidomide-dexamethasone [CTD] followed by high-dose therapy plus autologous stem cell transplantation for younger/fitter patients [intensive pathway], and melphalan-prednisone (MP) or attenuated CTD [CTDa] for older/less fit patients [non-intensive pathway]). At second randomization, patients were assigned to thalidomide maintenance therapy or no maintenance. Interphase FISH (iFISH) was used to analyze cytogenics.

Results: Zoledronic acid significantly improved progression-free survival (PFS; hazard ratio [HR], 0.89; P = 0.02) and overall survival (OS; HR, 0.86; P = 0.01) compared with clodronic acid. In the intensive pathway, CTD demonstrated non-inferior PFS and OS compared with CVAD, with a trend toward improved OS in patients with favorable cytogenics (P = 0.068). In the non-intensive pathway, CTDa significantly improved PFS (HR, 0.81; P = 0.007) compared with MP and there was an emergent survival benefit after 18-24 months. Thalidomide maintenance improved PFS (HR, 1.44; P < 0.0001) but not OS (HR, 0.96; P = 0.70), and was associated with shorter OS in patients with adverse cytogenics (P = 0.01).

Conclusions: Long-term follow-up is essential to identify clinically meaningful treatment effects in myeloma subgroups based on cytogenetics.

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More information

Accepted/In Press date: 30 August 2013
e-pub ahead of print date: 30 August 2013
Published date: November 2013
Keywords: bisphosphonate, clodronic acid, zoledronic acid, multiple myeloma, cyclophosphamide-thalidomide-dexamethasone (CTD)
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 356387
URI: http://eprints.soton.ac.uk/id/eprint/356387
ISSN: 1078-0432
PURE UUID: a6c3c195-5c21-4687-a828-321bb8336ec4

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Date deposited: 25 Sep 2013 13:19
Last modified: 22 Jul 2022 18:44

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Contributors

Author: Gareth J. Morgan
Author: Faith E. Davies
Author: Walter M. Gregory
Author: Susan E. Bell
Author: Alexander J. Szubert
Author: Gordon Cook
Author: Mark T. Drayson
Author: Roger G. Owen
Author: Fiona M. Ross
Author: Graham H. Jackson
Author: J. Anthony Child

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