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.
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.


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.


CONCLUSIONS
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).
Johnsen
Hans E
HE
Department of Haematology, Herlev Hospital, Copenhagen University, Denmark. haej@rn.dk
Klausen
Tobias W
TW
Boegsted
Martin
M
Lenhoff
Stig
S
Gimsing
Peter
P
Christiansen
Ilse
I
Gedde-Dahl
Tobias
T
Lindås
Roald
R
Mellqvist
Ulf-Henrik
UH
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003718:Denmark; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality* / Q000628:therapy*; D009664:Norway; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D015983:Selection Bias; D013548:Sweden; D014182:Transplantation, Autologous
D007372:Interferons; D008558:Melphalan; D011241:Prednisone