Abstract

Abstract 3094

Background:

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment for patients with multiple myeloma (MM) but its use is limited by high non-relapse mortality (NRM). European Group for Bone Marrow transplant (EBMT) risk score is a validated predictor of outcome for patients undergoing allo-HCT for hematological malignancies. It takes into consideration patient's age, donor's gender and type, disease status and the interval from diagnosis to allo-HCT, with the score ranging from 0 to 7. We assessed the impact of EBMT risk score in MM patients undergoing allo-HCT.

Methods:

A total of 189 patients with MM who underwent HSCT between November 1985 and June 2010 at MD Anderson Cancer Center were included in the analysis.

Results:

Patient characteristics are summarized in Table 1. There were 110 males (58%) and 79 females (42%) with a mean age of 50 years (range 28–70). Donors were related in 146 patients (HLA-identical=131, 1 antigen mismatched (AGMM) = 5, 2 AGMM =1, 3AGMM=1, syngeneic=8) and unrelated in 43 patients (HLA identical= 37, 1AGMM=4, 2AGMM=1, unknown=1). One-hundred and twelve patients had prior autologous transplants (auto-HCT). Of these 83 had 1, 28 had 2 and 1 had 3 prior auto-HCT, respectively. Median time from diagnosis to allo-HCT was 24.7 months (range 3.3–232) and median overall follow up was 13 months (0.2–266). Overall 94 patients (49%) had progressed before last follow-up. Incidence of all-cause mortality was 138 (73.4%) with 69 (36%) of all deaths attributed to NRM. KM estimates of 2-year PFS and OS were 25% and 42%, and 5-year PFS and OS were 16% and 27%, respectively. Cumulative incidence (CI) of grade 2–4 and grade 3–4 acute graft versus host disease (aGVHD) was 33% and 13%, respectively. Cumulative incidence of overall and extensive chronic GVHD (cGVHD) was 47% and 17%, respectively. EBMT risk score was, 0–3 for 41 (21.7%), 4 for 72 (38.1%) 4 and 5–7 for 76 (40.2%) patients. EBMT risk score was higher for males, African-Americans and older allo-HCT recipients, patients with higher LDH levels (>618mg/dl), ß2-microglobulin >3.5mg/dl and patients with bone marrow plasmacytosis. Median PFS in patients with EBMT scores 0–3, 4 and 5–7 were 10.1, 8.4 and 6.4 months, respectively (P=0.0036). Median OS in patients with EBMT scores 0–3, 4 and 5–7 were 39, 15.8 and 9.6 months, respectively (p=0.001). Cumulative NRM in patients with EBMT scores 0–3, 4 and 5–7 were 37% (15/41), 36.1% (26/72) and 37.3% (28/75), respectively (p= 0.234). Cumulative incidence of progression in patients with EBMT scores 0–3, 4 and 5–7 were 36.5% (15/41), 50% (36/72) and 56.5% (43/76), p=0.119. Compared to those with EBMT risk score (0–3), individuals with EBMT risk scores >5 had a higher risk of all-cause mortality (HR 2.34, 95% CI 1.44–3.80), and disease progression (HR 3.06, 95% CI 1.67–5.61). Addition of ß2-microglobulin, BM plasma cells or prior response status alone or in combination with EBMT risk score significantly improved the discrimination properties of the model containing EBMT score alone (p<0.05).

Conclusions:

EBMT risk score is an independent predictor of survival in MM patients undergoing allo-HCT. Addition of myeloma-specific factors predictors (ß2-microglobulin, plasma cell infiltration and prior response status) to EBMT score significantly improves its prognostic impact.

Table 1:

Correlates of EBMT score with relevant clinical characteristics

VariableNo of subjects 189Mean (SD) or %Change compared to reference category or per 1SD
EBMT Score  4.24 (1.18)  
Age at transplant (yrs.)  50 (8) 0.25 (0.08 to 0.41) 
Gender    
    Female 79 42% ref 
    Male 110 58% 0.64 (0.31 to 0.96) 
Race 189   
    White 135 71% ref 
    Black 23 12% 0.10 (−0.43 to 0.62) 
    Other 31 16% −0.12 (−0.58 to 0.34) 
Durie Salmon Stage 189   
    I 19 10% ref 
    II 71 38% 0.02 (−0.58 to 0.62) 
    III 97 51% −0.15 (-0.73 to 0.43) 
    Unk 1% −0.32 (−2.04 to 1.41) 
Disease status 189   
    First remission consolidation 47 25% ref 
    Relapsed 142 75% 1.09 (0.73 to 1.45) 
Prior response 189   
    >/= PR 106 56% ref 
    <PR 83 44% 1.01 (0.70 to 1.31) 
BM Plasma Cells 181   
    <10 130 72% ref 
    >10 51 28% 0.88 (0.52 to 1.24) 
LDH(mg/dl) 189   
    <618 158 84% ref 
    >618 31 16% 0.33 (−0.13 to 0.78) 
    ß2-microglobulin(mg/l) 182   
    <3.5 128 70% ref 
    >3.5 54 30% 0.37 (−0.01 to 0.74) 
VariableNo of subjects 189Mean (SD) or %Change compared to reference category or per 1SD
EBMT Score  4.24 (1.18)  
Age at transplant (yrs.)  50 (8) 0.25 (0.08 to 0.41) 
Gender    
    Female 79 42% ref 
    Male 110 58% 0.64 (0.31 to 0.96) 
Race 189   
    White 135 71% ref 
    Black 23 12% 0.10 (−0.43 to 0.62) 
    Other 31 16% −0.12 (−0.58 to 0.34) 
Durie Salmon Stage 189   
    I 19 10% ref 
    II 71 38% 0.02 (−0.58 to 0.62) 
    III 97 51% −0.15 (-0.73 to 0.43) 
    Unk 1% −0.32 (−2.04 to 1.41) 
Disease status 189   
    First remission consolidation 47 25% ref 
    Relapsed 142 75% 1.09 (0.73 to 1.45) 
Prior response 189   
    >/= PR 106 56% ref 
    <PR 83 44% 1.01 (0.70 to 1.31) 
BM Plasma Cells 181   
    <10 130 72% ref 
    >10 51 28% 0.88 (0.52 to 1.24) 
LDH(mg/dl) 189   
    <618 158 84% ref 
    >618 31 16% 0.33 (−0.13 to 0.78) 
    ß2-microglobulin(mg/l) 182   
    <3.5 128 70% ref 
    >3.5 54 30% 0.37 (−0.01 to 0.74) 

<PR, includes Stable Disease, No Response, PD; >=PR: includes Complete Remission (CR); Complete Cytogenetic Response (CCR), Very Good Partial Response and Partial Remission (VGPR)

PR: Partial remission, BM: bone marrow

Disclosures:

Giralt:Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Author notes

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Asterisk with author names denotes non-ASH members.