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Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report

Antonio Palumbo, Sara Bringhen, Maria-Victoria Mateos, Alessandra Larocca, Thierry Facon, Shaji K. Kumar, Massimo Offidani, Philip McCarthy, Andrea Evangelista, Sagar Lonial, Sonja Zweegman, Pellegrino Musto, Evangelos Terpos, Andrew Belch, Roman Hajek, Heinz Ludwig, A. Keith Stewart, Philippe Moreau, Kenneth Anderson, Hermann Einsele, Brian G. M. Durie, Meletios A. Dimopoulos, Ola Landgren, Jesus F. San Miguel, Paul Richardson, Pieter Sonneveld and S. Vincent Rajkumar
This article has an Erratum 127(9):1213
This article has an Erratum 128(7):1020

Data supplements

Article Figures & Data

Figures

  • Figure 1

    Long-term outcomes. (A) OS, (B) PFS, and (C) cumulative incidence of hematologic adverse events, (D) nonhematologic adverse events, and (E) discontinuation in the intention-to-treat population.

Tables

  • Table 1

    Baseline patient characteristics

    No. of patients, N = 869% of patientsMedian (IQR)
    Age, y74 (70-78)
     ≤65162
     65-7445152
     ≥7540246
     ≥8016119
    Creatinine, mg/dL0.98 (0.80-1.22)
     <280292
     ≥2375
     Missing303
    ECOG PS
     025830
     139846
     216619
     3142
    ISS
     I23928
     II36142
     III26931
    Chromosome abnormalities
     t(4;14)809
     t(14;16)223
     del17p1310512
     Missing14717
     Unfavorable profile32938
    ADL6 (5-6)
     >475086
     ≤411914
    IADL8 (6-8)
     >571382
     ≤515618
    CCI0 (0-1)
     ≤172583
     ≥214417
    Therapy
     Lenalidomide-containing regimens65976
     Proteasome inhibitor-containing regimens21024
    • Unfavorable profile defined as t(4;14) or t(14;16) or del17p13.

    • ADL, Activity of Daily Living; CCI, Charlson Comorbidity Index; ECOG PS, Eastern Cooperative Oncology Group performance status; IADL, Instrumental Activity of Daily Living; IQR, interquartile range; ISS, International Staging System.

  • Table 2

    The final Cox regression model

    HR (95% CI)PScore
    Age, y
     ≤7510
     76-801.13 (0.76-1.69).5491
     >802.40 (1.56-3.71)<.0012
    ADL
     >410
     ≤41.67 (1.08-2.56).0201
    IADL
     >510
     ≤51.43 (0.96-2.14).0781
    CCI
     ≤110
     ≥21.37 (0.92-2.05).1251
    ISS
     I1
     II2.37 (1.38-4.09).002
     III3.21 (1.85-5.58)<.001
    Chromosome abnormalities
     Favorable1
     Unfavorable1.79 (1.23-2.60).002
     Missing1.13 (0.69-1.83).036
    Therapy
     Proteasome inhibitors1
     Lenalidomide0.74 (0.50-1.11).142
    • HRs and relative risks are for OS in patients with the factors as compared with those without the factors. The model was adjusted for ISS, chromosome abnormalities, and therapy. Unfavorable profile defined as t(4;14) or t(14;16) or del17p13.

    • AIC = 1748.918; Harrell C index = 0.7069.

  • Table 3

    Additive total score and related rate of OS and PFS at 3 years

    Additive total scorePatient statusNo. of patients (%)% (95% CI)Cumulative incidence at 12 mo, %
    OSPFSTreatment discontinuationGrade 3-4 nonhematologic AEs
    0Fit340 (39)84 (78-89)48 (41-56)1622
    1Intermediate-fitness269 (31)76 (67-82)41 (32-49)2126
    ≥2Frail260 (30)57 (45-68)33 (25-41)3134
    • In the univariate Cox model, the Harrell C index = 0.6608 and the AIC = 1766.077. In the multivariate Cox model, the Harrell C index = 0.7092 and the AIC = 1743.353.

  • Table 4

    Univariate and multivariate analysis of the impact of the frailty profile of patients on OS, PFS, discontinuation rate, and incidence of grade 3 or higher toxicity

    OSPFSDiscontinuationGrade ≥3 hematologic toxicityGrade ≥3 nonhematologic toxicity
    HR (95% CI)PHR (95% CI)PHR (95% CI)PHR (95% CI)PHR (95% CI)P
    Crude
     Fit11111
     Intermediate fitness1.61 (1.02-2.56).0421.18 (0.91-1.53).2111.48 (1.05-2.10).0260.97 (0.74-1.27).8081.23 (0.89-1.71).217
     Frail3.57 (2.37-5.39)<.0011.68 (1.31-2.15)<.0012.27 (1.64-3.14)<.0010.83 (0.62-1.09).1811.74 (1.28-2.38)<.001
    Adjusted*
     Fit11111
     Intermediate fitness1.37 (0.86-2.18).1811.08 (0.83-1.40).5831.41 (1.00-2.01).0520.97 (0.74-1.28).8311.13 (0.81-1.58).462
     Frail2.88 (1.88-4.40)<.0011.48 (1.15-1.92).0032.21 (1.57-3.09)<.0010.94 (0.71-1.26).6981.57 (1.12-2.19).008
    • * Adjusted for ISS, chromosome abnormalities, and therapy.