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Improved Survival for Multiple Myeloma in Denmark Based on Autologous Stem Cell Transplantation and Novel Drug Therapy in Collaborative Trials: Analysis of Accrual, Prognostic Variables, Selection Bias, and Clinical Behavior on Survival in More Than 1200 Patients in Trials of the Nordic Myeloma Study Group

Johnsen, Hans E.; Klausen, Tobias W.; Boegsted, Martin; Lenhoff, Stig LU ; Gimsing, Peter; Christiansen, Ilse; Gedde-Dahl, Tobias; Lindas, Roald and Mellqvist, Ulf-Henrik (2010) In Clinical Lymphoma, Myeloma & Leukemia 10(4). p.290-296
Abstract
Background: An unexplained survival difference was observed in the Nordic Myeloma Study Group (NMSG) high-dose therapy trial 5/94 in Denmark compared with Sweden and Norway; however, this difference was eliminated in the subsequent NMSG trial 7/98. It was hypothesized that a detailed analysis of potential explanations would reveal important information for future designs of clinical trials for multiple myeloma (MM) patients in Denmark. Patients and Methods: The analysis is based on 3 consecutive clinical trials coordinated by NMSG from 1990 to 2000: NMSG 4/90 including 583 patients, NMSG 5/94 including 274 patients and NMSG 7/98 including 414 patients with newly diagnosed MM. Event-free and total survival rates were calculated according to... (More)
Background: An unexplained survival difference was observed in the Nordic Myeloma Study Group (NMSG) high-dose therapy trial 5/94 in Denmark compared with Sweden and Norway; however, this difference was eliminated in the subsequent NMSG trial 7/98. It was hypothesized that a detailed analysis of potential explanations would reveal important information for future designs of clinical trials for multiple myeloma (MM) patients in Denmark. Patients and Methods: The analysis is based on 3 consecutive clinical trials coordinated by NMSG from 1990 to 2000: NMSG 4/90 including 583 patients, NMSG 5/94 including 274 patients and NMSG 7/98 including 414 patients with newly diagnosed MM. Event-free and total survival rates were calculated according to the Kaplan-Meier method, and survival comparisons were made by the log-rank test. The Cox proportional hazards regression model was used to estimate the prognostic importance of selected variables. Results: The analysis revealed no differences in disease stages, prognostic variables, or inclusion bias at diagnosis between the 3 consecutive NMSG trials. However, the number of initial treatment failures was low, and post-relapse survival was superior in Swedish patients as compared to Danish patients. These differences were explained by a defensive clinical practice in Denmark during 1994-1997 for patients with poor risk refractory or relapsed disease. Conclusion: These initially observed differences were subsequently eliminated most likely as a consequence of international collaboration improving diagnosis, research infrastructure, clinical training, and education as planned within the European Myeloma Network (EMN). (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
European, Myeloma Network, Prognosis, Bone marrow plasma, beta(2)-microglobulin, Blood hemoglobin
in
Clinical Lymphoma, Myeloma & Leukemia
volume
10
issue
4
pages
290 - 296
publisher
CIG Media Group
external identifiers
  • wos:000280592400009
  • scopus:77957070224
ISSN
2152-2650
DOI
10.3816/CLML.2010.n.060
language
English
LU publication?
yes
id
b0c4cc1f-9541-4ce0-abf1-0c06193b5917 (old id 1678464)
date added to LUP
2010-09-21 09:29:17
date last changed
2018-05-29 09:20:35
@article{b0c4cc1f-9541-4ce0-abf1-0c06193b5917,
  abstract     = {Background: An unexplained survival difference was observed in the Nordic Myeloma Study Group (NMSG) high-dose therapy trial 5/94 in Denmark compared with Sweden and Norway; however, this difference was eliminated in the subsequent NMSG trial 7/98. It was hypothesized that a detailed analysis of potential explanations would reveal important information for future designs of clinical trials for multiple myeloma (MM) patients in Denmark. Patients and Methods: The analysis is based on 3 consecutive clinical trials coordinated by NMSG from 1990 to 2000: NMSG 4/90 including 583 patients, NMSG 5/94 including 274 patients and NMSG 7/98 including 414 patients with newly diagnosed MM. Event-free and total survival rates were calculated according to the Kaplan-Meier method, and survival comparisons were made by the log-rank test. The Cox proportional hazards regression model was used to estimate the prognostic importance of selected variables. Results: The analysis revealed no differences in disease stages, prognostic variables, or inclusion bias at diagnosis between the 3 consecutive NMSG trials. However, the number of initial treatment failures was low, and post-relapse survival was superior in Swedish patients as compared to Danish patients. These differences were explained by a defensive clinical practice in Denmark during 1994-1997 for patients with poor risk refractory or relapsed disease. Conclusion: These initially observed differences were subsequently eliminated most likely as a consequence of international collaboration improving diagnosis, research infrastructure, clinical training, and education as planned within the European Myeloma Network (EMN).},
  author       = {Johnsen, Hans E. and Klausen, Tobias W. and Boegsted, Martin and Lenhoff, Stig and Gimsing, Peter and Christiansen, Ilse and Gedde-Dahl, Tobias and Lindas, Roald and Mellqvist, Ulf-Henrik},
  issn         = {2152-2650},
  keyword      = {European,Myeloma Network,Prognosis,Bone marrow plasma,beta(2)-microglobulin,Blood hemoglobin},
  language     = {eng},
  number       = {4},
  pages        = {290--296},
  publisher    = {CIG Media Group},
  series       = {Clinical Lymphoma, Myeloma & Leukemia},
  title        = {Improved Survival for Multiple Myeloma in Denmark Based on Autologous Stem Cell Transplantation and Novel Drug Therapy in Collaborative Trials: Analysis of Accrual, Prognostic Variables, Selection Bias, and Clinical Behavior on Survival in More Than 1200 Patients in Trials of the Nordic Myeloma Study Group},
  url          = {http://dx.doi.org/10.3816/CLML.2010.n.060},
  volume       = {10},
  year         = {2010},
}