Article

Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease

University of Arkansas at Little Rock, Little Rock, Arkansas, United States
British Journal of Haematology (Impact Factor: 4.96). 03/2007; 136(3):393-9. DOI: 10.1111/j.1365-2141.2006.06441.x
Source: PubMed

ABSTRACT Complete response (CR) is still considered an important surrogate marker for outcome in multiple myeloma (MM). Long-term survival after transplantation, however, has been observed in a substantial proportion of patients who never achieved CR. The tandem transplant trial, Total Therapy 2, enrolled 668 patients, who were randomised up-front to thalidomide (THAL) or no THAL; 56 patients were identified as having had, for at least 6 months prior to initiation of therapy, monoclonal gammopathy of undetermined significance (MGUS, n = 21), smouldering MM (SMM, n = 22) or solitary plasmacytoma of bone (SPC, n = 13). The clinical characteristics and outcomes of patients with such 'evolved' MM (E-MM) and of those with 'unknown' prior history (U-MM) were compared. Fewer patients with MGUS/SMM-E-MM had anaemia or renal failure; CR was lower (22% vs. 48%) but 4-year estimates of event-free survival (54% vs. 56% with U-MM) and overall survival (65% vs. 70% with U-MM) were similar to those with SPC-E-MM or U-MM. In the latter group, achieving CR was associated with prolonged survival. In comparison with U-MM, E-MM evolved from MGUS/SMM was associated with lower CR rate without adversely affecting survival. In contrast, CR was an independent favourable feature for survival in U-MM.

0 Followers
 · 
61 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple myeloma is an incurable neoplastic disorder of B cells characterized by diffuse bone marrow infiltration, circumscribed bone lesions, and soft-tissue spreading. The role of novel functional imaging techniques in multiple myeloma includes initial staging of the disease, detection and characterization of complications, and evaluation of the response to treatment.
    Orvosi Hetilap 08/2014; 155(31):1241-5. DOI:10.1556/OH.2014.29881
  • [Show abstract] [Hide abstract]
    ABSTRACT: L-type amino-acid transporter 1 (LAT1) plays a key role in cell growth and survival. To determine the prognostic significance of LAT1 in multiple myeloma (MM), we investigated the expression of LAT1 and its functional subunit, 4Fc heavy chain (CD98), on myeloma cells by immunohistochemistry in 100 newly diagnosed MM patients. High expression (moderate or strong staining intensity) of LAT1 and CD98 was detected in 56% and 45% of patients, respectively. The LAT1 expression score was positively correlated with Ki-67 index (r=0.631, p<0.001), and there was a statistically significant difference in Durie-Salmon stage between patients with high and low LAT1 expression (p=0.03). In 43 patients treated with melphalan and prednisolone, overall response rate was significantly higher in the high LAT1 expression group (60.0%) than in the low LAT1 expression group (17.6%) (p=0.03). Multivariate analysis confirmed that high expression of LAT1 was a significant prognostic factor for predicting poor overall survival independently from the International staging system (both p=0.01). Here, we show that the overexpression of LAT1 is significantly associated with high proliferation and poor prognosis in newly diagnosed MM patients. Thus, LAT1 may be a promising pathological marker for identifying high-risk MM.This article is protected by copyright. All rights reserved.
    Cancer Science 09/2014; DOI:10.1111/cas.12529 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We examine whether the historical dogma of multiple myeloma being incurable still holds true. The genomic chaos and resulting resistance to apoptosis of myeloma, long considered an obstacle to cure, formed the basis of the Arkansas Total Therapy (TT) program. The TT approach employs all myeloma-active drugs up-front to target drug-resistant sub-clones during initial treatment to prevent later relapse. Long-term follow up of altogether 1202 patients enrolled (TT1: n=231, median follow up: 21yr; TT2: 668, median follow up: 12yr; TT3a: n=303, median follow up: 9yr) permitted investigation of whether progression-free survival (PFS) and complete response (CR) duration were consistent with curability, i.e. observation of plateaus in Kaplan-Meier plots for PFS and CR duration. In the subset of 627 patients with plasma cell gene expression profiling data, cure plateaus were apparent at 5 years in the 14% with high-risk myeloma compared to 10 years in the remainder with low-risk disease. A parametric model based on PFS and CR duration supported an increase in curability with successive trials. Thus, 10-yr PFS and CR estimates increased from 8.8%/17.9% in TT1 to 15.5%/28.2% in TT2's control arm to 25.1%/35.6% in TT2's thalidomide arm and to 32.9/48.8% in TT3a. Toward developing novel therapies, we recommend a concerted focus on patients with high-risk myeloma whose outcome has not been advanced.
    Blood 10/2014; 124(20). DOI:10.1182/blood-2014-07-552059 · 9.78 Impact Factor

Preview

Download
0 Downloads