Abstract
Abstract 1962
Older age and higher serum creatinine levels have long been considered adverse features for overall survival (OS) and progression-free survival (PFS) in MM. Here we are reporting on these variables and their impact on clinical outcomes with the evolution of TT protocols. Among patients <55yr, median OS was 6.4yr with TT1 with 30% alive at 15yr and 12.2yr with TT2. KM curves for TT2 and TT3 were superimposable and medians have not been reached for TT3. (p<0.0001) (Figure 1). The proportions alive were 30% at 15yr in TT1, 60% at 10yr in TT2, and 80% at 5yr in TT3. Median PFS was 2.7yr with TT1, 6.0yr with TT2, and not reached with TT3; ∼10% remain event-free from 15 to 20 years in TT1, 40% at 10yr in TT2, and almost 60% at 5yr in TT3 (p<0.0001). For the middle age group 55–64yr, 15% are alive at 15yr in TT1, 40% at 10yr in TT2, and 75% at 5yr in TT3 (p=0.006). The corresponding PFS was ∼10% at 15yr with TT1, 25% at 10yr with TT2, and 70% at 5yr with TT3 (p<0.0001). For patients >64yr, median OS was 3.3yr with TT1, 6.5yr with TT2, and not reached with TT3 (p=0.01); 15% are alive at 10yr with TT1, 30% at 10yr with TT2, 70% at 5yr with TT3. PFS was 1.9yr with TT1, 3.8yr with TT2 and not reached with TT3; No patients remain at 16yr with TT1, 30% at 10yr with TT2, and 65% at 5yr with TT3. Within protocols, age effects on OS were most apparent in TT1; with TT2 those <55yr outperformed the 2 older age groups, and no significant age difference was apparent for TT3. As to renal function, creatinine >=2 mg/dL was significantly linked to inferior OS in all 3 trials, with medians of 3.6yr v 6.1yr in TT1, 4.1yr v 9.1yr in TT2, and ∼50% v 75% alive at 5yr in TT3 (p=0.008,p=0.001,p=0.002) (Figure 2). PFS was 2.5yr with TT1 regardless of renal function(p=0.36), 3yr v 4.9yr with TT2 (p=0.002), and ∼40% v 70% at 5yr with TT3 (p<0.0001). Thus, major advances in both OS (p<0.0001) and PFS (p<0.0001) were observed with the transition from TT1 to TT2 to TT3 among patients with creatinine <2 mg/dL, whereas results remained dismal for the more impaired renal function group (OS: p=0.22, PFS: p=0.42). Accounting for all possible interactions between TT trial, age, and creatinine, multivariate logistic regression to predict 4-yr OS and 4-yr PFS showed consistently improved OR for OS with TT3>TT2>TT1 regardless of age groups; 4-yr PFS also benefited from TT3>TT2>TT1, but this was most clearly seen in the 55–64yr age group. Significant interactions with creatinine were not observed but levels >=2mg/dL remained an independent dominant adverse variable (OS: OR=2.31, p<0.0001; PFS: OR=2.11, p<0.0001) (Table 1). In conclusion, treatment advances have been realized in patients with preserved renal function across age groups. The poor outcome in patients with creatinine >=2.0mg/dL may not only reflect host- but also MM-related issues. Delaying more toxic VTD-PACE induction until improvement in renal function with VTD for 1 or 2 cycles may improve clinical outcomes.
Endpoint . | OR Comparison . | OR (95% CI) . | p-value . |
---|---|---|---|
4-year OS | TT2 v TT1 | 0.58 (0.42, 0.81) | 0.0013 |
TT3 v TT2 | 0.77 (0.59, 1.01) | 0.0623 | |
Age 55–64 v Age < 55 | 1.77 (1.34, 2.34) | <.0001 | |
Age >= 65 v Age 55–64 | 1.25 (0.92, 1.71) | 0.1596 | |
Cr >= 2mg/dL | 2.31 (1.57, 3.41) | <.0001 | |
4-year PFS | TT2 v TT1 Age < 55 | 0.28 (0.18, 0.43) | <.0001 |
TT3 v TT2 Age < 55 | 0.75 (0.49, 1.15) | 0.1881 | |
TT2 v TT1 Age 55–64 | 0.55 (0.31, 0.99) | 0.0463 | |
TT3 v TT2 Age 55–64 | 0.33 (0.22, 0.51) | <.0001 | |
TT2 v TT1 Age >= 65 | 0.63 (0.25, 1.64) | 0.3459 | |
TT3 v TT2 Age >= 65 | 0.59 (0.36, 0.97) | 0.0385 | |
Cr >= 2mg/dL | 2.11 (1.41, 3.16) | 0.0003 |
Endpoint . | OR Comparison . | OR (95% CI) . | p-value . |
---|---|---|---|
4-year OS | TT2 v TT1 | 0.58 (0.42, 0.81) | 0.0013 |
TT3 v TT2 | 0.77 (0.59, 1.01) | 0.0623 | |
Age 55–64 v Age < 55 | 1.77 (1.34, 2.34) | <.0001 | |
Age >= 65 v Age 55–64 | 1.25 (0.92, 1.71) | 0.1596 | |
Cr >= 2mg/dL | 2.31 (1.57, 3.41) | <.0001 | |
4-year PFS | TT2 v TT1 Age < 55 | 0.28 (0.18, 0.43) | <.0001 |
TT3 v TT2 Age < 55 | 0.75 (0.49, 1.15) | 0.1881 | |
TT2 v TT1 Age 55–64 | 0.55 (0.31, 0.99) | 0.0463 | |
TT3 v TT2 Age 55–64 | 0.33 (0.22, 0.51) | <.0001 | |
TT2 v TT1 Age >= 65 | 0.63 (0.25, 1.64) | 0.3459 | |
TT3 v TT2 Age >= 65 | 0.59 (0.36, 0.97) | 0.0385 | |
Cr >= 2mg/dL | 2.11 (1.41, 3.16) | 0.0003 |
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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