Remission status defined by immunofixation vs. electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients.
We have retrospectively analysed 344 multiple myeloma (MM) patients (202 de novo patients) treated in a non-uniform way in whom high-dose therapy and autologous stem cell transplantation (ASCT) response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF). Patients in complete remission (CR) by EP were further subclassified as CR1 when IF was negative and CR2 when it remained positive. Partial responders (PR) were also subclassified as PR1 (very good PR, > 90% reduction in M-component) or PR2 (50-90% reduction). CR1 patients showed a significantly better event-free survival (EFS) [35% at 5 years, 95% confidence interval (CI) 17-53, median 46 months] and overall survival (OS) (72% at 5 years, CI 57-86, median not reached) compared with any other response group (univariate comparison P < 0.00000 to P = 0. 004). In contrast, comparison of CR2 with PR1 and with PR2 did not define different prognostic subgroups (median EFS 30, 30 and 26 months respectively, P = 0.6; median survival 56, 44 and 42 months respectively, P = 0.5). The non-responding patients had the worst outcome (5-year OS 8%, median 7 months). Multivariate analysis confirmed both the absence of differences among CR2, PR1 and PR2 and the highly discriminatory prognostic capacity of a three-category classification: (i) CR1 (ii) CR2 + PR1 + PR2, and (iii) non-response (EFS P < 0.00000; OS P < 0.00000; both Cox models P < 0.00000). In the logistic regression analysis, the factors significantly associated with failure to achieve CR1 were the use of two or more up-front chemotherapy lines, status of non-response pre-ASCT and inclusion of total body irradiation (TBI) in the preparative regimen. Tandem transplants or the use of multiple agents (busulphan and melphalan) in the preparative regimen resulted in a higher CR1 level; none of the biological factors explored influenced the possibility of achieving CR1. These results confirm that, in MM patients undergoing ASCT, achieving a negative IF identifies the patient subset with the best prognosis; accordingly, therapeutic strategies should be specifically designed to achieve negative IF.
Lahuerta
J J
JJ
Spanish Stem Cell Transplantation Group and Programme for the Study and Treatment of Haematological Malignancies, Spanish Society of Haematology, Madrid, Spain. lahuerta@serconet.com
Martinez-Lopez
J
J
Serna
J D
JD
Bladé
J
J
Grande
C
C
Alegre
A
A
Vazquez
L
L
García-Laraña
J
J
Sureda
A
A
Rubia
J D
JD
Conde
E
E
Martinez
R
R
Perez-Equiza
K
K
Moraleda
J M
JM
León
A
A
Besalduch
J
J
Cabrera
R
R
Miguel
J D
JD
Morales
A
A
García-Ruíz
J C
JC
Diaz-Mediavilla
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J
San-Miguel
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J
D004586:Electrophoresis; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D015999:Multivariate Analysis; D010266:Paraproteins / Q000652:urine; D011233:Precipitin Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D010266:Paraproteins