Table 3

Variables linked to TNT

Variablen/N (%)TNT from enrollment
HR (95% CI)P
Univariate analysis    
    β2M > 5.5 mg/L 65/303 (21) 1.67 (1.09, 2.56) .018 
    Creatinine ≥ 2 mg/dL 23/303 (8) 1.90 (1.04, 3.45) .036 
    Hb < 10 g/dL 94/303 (31) 1.55 (1.06, 2.27) .025 
    LDH ≥ 190 U/L 81/303 (27) 2.05 (1.39, 3.02) < .001 
    Cytogenetic abnormalities 100/302 (33) 2.40 (1.66, 3.48) < .001 
    GEP high-risk 40/275 (15) 2.74 (1.71, 4.40) < .001 
    GEP proliferation subgroup 27/275 (10) 2.05 (1.17, 3.59) .013 
        GEP NR3C1 bottom tertile 91/274 (33) 1.07 (0.71, 1.60) .747 
        GEP NR3C1 top tertile 91/274 (33) 0.77 (0.51, 1.15) .202 
        Completed transplantation 2* — 0.64 (0.38, 1.09) .102 
        Completed consolidation 1* — 0.82 (0.48, 1.37) .444 
        Completed consolidation 2* — 1.02 (0.62, 1.66) .946 
        Bortezomib during induction (mg)* — 0.94 (0.86, 1.02) .133 
        Bortezomib during consolidation (mg)* — 0.99 (0.96, 1.02) .397 
        Bortezomib during maintenance (mg)* — 1.00 (0.99, 1.00) .136 
    Dexamethasone during induction (dg)* — 0.77 (0.62, 0.96) .022 
    Dexamethasone during transplantation (dg)* — 0.92 (0.85, 0.99) .034 
        Dexamethasone during consolidation (dg)* — 0.95 (0.90, 1.02) .148 
        Dexamethasone during maintenance (dg)* — 0.98 (0.95, 1.00) .060 
        Thalidomide during induction (g)* — 0.84 (0.64, 1.12) .232 
        Thalidomide during transplantation (g)* — 1.02 (0.96, 1.07) .517 
        Thalidomide during consolidation (g)* — 1.01 (0.98, 1.05) .458 
        Thalidomide during maintenance (g)* — 1.00 (0.98, 1.01) .407 
    Premature bortezomib discontinuation* — 8.57 (5.09, 14.42) < .001 
    Premature dexamethasone discontinuation* — 8.16 (4.81, 13.86) < .001 
    Premature thalidomide discontinuation* — 8.52 (4.98, 14.57) < .001 
    Achieved CR* — 0.47 (0.32, 0.69) < .001 
        Achieved CR before Tx2* — 0.67 (0.41, 1.10) .113 
Multivariate analysis    
    LDH ≥ 190 U/L 74/275 (27) 1.62 (1.05, 2.49) .028 
    Cytogenetic abnormalities 95/275 (35) 2.16 (1.42, 3.29) < .001 
    GEP high-risk 40/275 (15) 1.74 (1.07, 2.85) .027 
        Premature dexamethasone discontinuation* — 2.47 (1.02, 5.98) .046 
        Premature thalidomide discontinuation* — 4.04 (1.66, 9.81) .002 
    Achieved CR* — 0.45 (0.29, 0.68) < .001 
Variablen/N (%)TNT from enrollment
HR (95% CI)P
Univariate analysis    
    β2M > 5.5 mg/L 65/303 (21) 1.67 (1.09, 2.56) .018 
    Creatinine ≥ 2 mg/dL 23/303 (8) 1.90 (1.04, 3.45) .036 
    Hb < 10 g/dL 94/303 (31) 1.55 (1.06, 2.27) .025 
    LDH ≥ 190 U/L 81/303 (27) 2.05 (1.39, 3.02) < .001 
    Cytogenetic abnormalities 100/302 (33) 2.40 (1.66, 3.48) < .001 
    GEP high-risk 40/275 (15) 2.74 (1.71, 4.40) < .001 
    GEP proliferation subgroup 27/275 (10) 2.05 (1.17, 3.59) .013 
        GEP NR3C1 bottom tertile 91/274 (33) 1.07 (0.71, 1.60) .747 
        GEP NR3C1 top tertile 91/274 (33) 0.77 (0.51, 1.15) .202 
        Completed transplantation 2* — 0.64 (0.38, 1.09) .102 
        Completed consolidation 1* — 0.82 (0.48, 1.37) .444 
        Completed consolidation 2* — 1.02 (0.62, 1.66) .946 
        Bortezomib during induction (mg)* — 0.94 (0.86, 1.02) .133 
        Bortezomib during consolidation (mg)* — 0.99 (0.96, 1.02) .397 
        Bortezomib during maintenance (mg)* — 1.00 (0.99, 1.00) .136 
    Dexamethasone during induction (dg)* — 0.77 (0.62, 0.96) .022 
    Dexamethasone during transplantation (dg)* — 0.92 (0.85, 0.99) .034 
        Dexamethasone during consolidation (dg)* — 0.95 (0.90, 1.02) .148 
        Dexamethasone during maintenance (dg)* — 0.98 (0.95, 1.00) .060 
        Thalidomide during induction (g)* — 0.84 (0.64, 1.12) .232 
        Thalidomide during transplantation (g)* — 1.02 (0.96, 1.07) .517 
        Thalidomide during consolidation (g)* — 1.01 (0.98, 1.05) .458 
        Thalidomide during maintenance (g)* — 1.00 (0.98, 1.01) .407 
    Premature bortezomib discontinuation* — 8.57 (5.09, 14.42) < .001 
    Premature dexamethasone discontinuation* — 8.16 (4.81, 13.86) < .001 
    Premature thalidomide discontinuation* — 8.52 (4.98, 14.57) < .001 
    Achieved CR* — 0.47 (0.32, 0.69) < .001 
        Achieved CR before Tx2* — 0.67 (0.41, 1.10) .113 
Multivariate analysis    
    LDH ≥ 190 U/L 74/275 (27) 1.62 (1.05, 2.49) .028 
    Cytogenetic abnormalities 95/275 (35) 2.16 (1.42, 3.29) < .001 
    GEP high-risk 40/275 (15) 1.74 (1.07, 2.85) .027 
        Premature dexamethasone discontinuation* — 2.47 (1.02, 5.98) .046 
        Premature thalidomide discontinuation* — 4.04 (1.66, 9.81) .002 
    Achieved CR* — 0.45 (0.29, 0.68) < .001 

Analyses were performed of cumulative doses per protocol step (induction, peritransplantation, consolidation, and maintenance). The multivariate model uses stepwise selection with entry level of 0.1 and variable remains if it meets the 0.05 level. Variables considered univariately were: age ≥ 65 years, female sex, white race, albumin < 3.5 g/dL, B2M ≥ 3.5 mg/L, B2M > 5.5 mg/L, creatinine ≥ 2 mg/dL, CRP ≥ 8 mg/L, Hb < 10 g/dL, LDH ≥ 190 U/L, cytogenetic abnormalities (anytime before enrollment), GEP high-risk, GEP CD-1 subgroup, GEP CD-2 subgroup, GEP hyperdiploidy subgroup, GEP low bone disease subgroup, GEP MAF/MAFB subgroup, GEP MMSET/FGFR3 subgroup, GEP myeloid subgroup, GEP proliferation subgroup, GEP TP53 deletion, GEP NR3C1 bottom tertile, GEP NR3C1 top tertile, completed transplantation 2*, completed consolidation 1*, completed consolidation 2*, bortezomib during induction*, bortezomib during consolidation*, bortezomib during maintenance*, dexamethasone during induction*, dexamethasone during transplantation*, dexamethasone during consolidation*, dexamethasone during maintenance*, thalidomide during induction*, thalidomide during transplantation*, thalidomide during consolidation*, thalidomide during maintenance*, premature bortezomib discontinuation*, premature dexamethasone discontinuation*, premature thalidomide discontinuation*, achieved CR*, and achieved CR before Tx2*. Variables considered for the multivariate model were: B2M > 5.5 mg/L, creatinine ≥ 2 mg/dL, Hb < 10 g/dL, LDH ≥ 190 U/L, cytogenetic abnormalities (anytime before enrollment), GEP high-risk, GEP proliferation subgroup, dexamethasone during induction*, dexamethasone during transplant*, premature bortezomib discontinuation*, premature dexamethasone discontinuation*, premature thalidomide discontinuation* and achieved CR*.

B2M indicates B2-microglobulin; CRP, C-reactive protein; Hb, hemoglobin; and —, not applicable.

*

Variable was treated as a time-dependent variable.

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