Remission status defined by immunofixation vs. electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients

Abstract

Summary. 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 threecategory classification: (i) CR1 (ii) CR2 1 PR1 1 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.

Attainment of at least a very good partial response after induction treatment is an important surrogate of longer survival for multiple myeloma

“…5,6,27,28 We have confirmed the prognostic effect of attaining XVGPR in both the transplant and non-transplant settings. We also show that the superior PFS accorded by achieving XVGPR was able to translate to a longer OS.…”

“…However, for transplant-eligible patients and those presenting with gene expression profiling-defined high-risk features, recent data have shown that the frontline treatment goal after HDT/auto-SCT should shift toward achieving a CR. [1][2][3][4][5][6][7][8][9] Sustainment of CR for at least 3 years from treatment initiation has also been shown to be especially important for patients presenting with high-risk disease. 10 Of late, the introduction of novel combinations entailing immunomodulatory agents such as thalidomide (THAL) or lenalidomide, together with bortezomib or melphalan for induction treatment, has resulted in superior CR rates that are comparable with those obtained with HDT/auto-SCT.…”

Autologous stem cell transplantation followed by consolidation chemotherapy for patients with multiple myeloma

“…7 Nonetheless, it should be emphasized that attainment of CR or near CR after autotransplantation is perhaps the most important predictor of long-term survival. 7,[19][20][21] Our data do show that incremental improvement in myeloma responses is possible during or after CC (an additional eight patients entered CR and 19 patients overall had objective improvements in response), suggesting that CC may have contributed to the observed EFS and OS rates. It is also noteworthy that 18 of the 24 (75%) patients who were surviving event-free at last follow-up had received three or four consolidation treatments.…”

Clinical outcomes with intensive therapy for patients with primary resistant multiple myeloma

“…8 Among those intensified during remission, we and others observed longer survival and relapse-free survival primarily among the one-third of patients converted to CR. [9][10][11] Prior rapid and marked reduction of myeloma with dexamethasone-based therapies were associated with even more frequent CR after intensive therapy, identifying prior tumor sensitivity as a predictive factor for CR. 11 Among patients whose disease had not responded to primary therapy, the role of intensive therapy has been less clear.…”