Advertisement

Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN)

Antonio Palumbo, Sara Bringhen, Heinz Ludwig, Meletios A. Dimopoulos, Joan Bladé, Maria V. Mateos, Laura Rosiñol, Mario Boccadoro, Michele Cavo, Henk Lokhorst, Sonja Zweegman, Evangelos Terpos, Faith Davies, Christoph Driessen, Peter Gimsing, Martin Gramatzki, Roman Hàjek, Hans E. Johnsen, Fernando Leal Da Costa, Orhan Sezer, Andrew Spencer, Meral Beksac, Gareth Morgan, Hermann Einsele, Jesus F. San Miguel and Pieter Sonneveld

Article Figures & Data

Figures

  • Figure 1

    Five-year relative survival rates according to the year of diagnosis and the patients' age at diagnosis. Survival rates have increased over the past 35 years in all patient age groups, a trend attributed to the effect of novel agents such as thalidomide, bortezomib, and lenalidomide; however, significant increases in survival have only been observed in patients aged < 65 years at initial diagnosis.3

  • Figure 2

    The interrelation between the 3 components of vulnerability (comorbidity, frailty, and disability) and the main health care implications associated with each factor.

Tables

  • Table 1

    Levels of frailty and disability in elderly patients and related description

    Frailty gradeDescription
    Very fitActive, energetic patients, who exercise regularly or occasionally
    Moderately fitPatients not regularly active beyond routinely walking
    VulnerablePatients who can perform limited activities but yet do not need help from other people
    Mildly frailPatients who need help for household tasks (shopping, walking several blocks, managing their finances, and medications)
    Moderately frailPatients who need partial help for their personal care (dressing, bathing, toileting, eating)
    Severely frailPatients completely dependent on other people for their personal care
  • Table 2

    Outcomes from randomized phase 3 clinical trials of different treatment regimens in elderly patients with NDMM

    RegimenMedian age, yDosingCR rate, %Median PFS, moMedian OS, moDiscontinuation rate, %Nonhematologic grade 3-4 AEs, %
    MPT4869M: 0.25 mg/kg on days 1-4 for twelve 6-wk cycles
    P: 40 mg/m2 on days 1-4 for twelve 6-wk cycles
    T: 400 mg/d for twelve 6-wk cycles
    1328524542
    MPT49,5072M: 4 mg/m2 on days 1-7 for six 4-wk cycles
    P: 40 mg/m2 on days 1-7 for six 4-wk cycles
    T: 100 mg/d until relapse
    1622453455*
    MPT5272M: 0.25 mg/kg on days 1-5 for eight 4-wk cycles
    P: 1 mg/kg on days 1-5 for eight 4-wk cycles
    T: 200 mg/d for eight 4-wk cycles, followed by 50 mg/d until relapse
    2313403650
    MPT5378M: 0.2 mg/kg on days 1-4 for twelve 6-wk cycles
    P: 2 mg/kg on days 1-4 for twelve 6-wk cycles
    T: 100 mg/d for twelve 6-wk cycles
    7244442NA
    MPT5474M: 0.25 mg/kg on days 1-4 for 6-wk cycles until plateau
    P: 100 mg/d on days 1-4 for 6-wk cycles until plateau
    T: 400 mg/d until plateau, reduced to 200 mg/d until progression
    1315293240
    MPT5569M: 9 mg/m2 on days 1-4 for eight 6-wk cycles
    P: 60 mg/m2 on days 1-4 for eight 6-wk cycles
    T: 100 mg/d for eight 6-wk cycles, followed by100 mg/d until relapse
    921§2616NA
    VMP47,5671V: 1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 for first four 6-wk cycles; days 1, 8, 15, and 22 for subsequent five 6-wk cycles
    M: 9 mg/m2 on days 1-4 for five 6-wk cycles
    P: 60 mg/m2 on days 1-4 for five 6-wk cycles
    30NANot reached3491*
    VMP5771V: 1.3 mg/m2 on days 1, 8, 15, and 22 for nine 5-wk cycles
    M: 9 mg/m2 on days 1-4 for nine 5-wk cycles
    P: 60 mg/m2 on days 1-4 for nine 5-wk cycles
    2423Not reached1733
    MPR-R58NAM: 0.18 mg/kg on days 1-4 for nine 4-wk cycles
    P: 2 mg/kg on days 1-4 for nine 4-wk cycles
    R: 10 mg on days 1-21 for nine 4-wk cycles
    R: 10 mg/d until relapse
    1631Not reached14NA
    Rd5166R: 25 mg on days 1-21
    d: 40 mg on days 1, 8, 15, 22 in 4-wk cycles
    425Not reached19NA
    VMPT5771V: 1.3 mg/m2 on days 1, 8, 15, and 22 for nine 5-wk cycles and on days 1, 15 until relapse
    M: 9 mg/m2 on days 1-4 for nine 5-wk cycles
    P: 60 mg/m2 on days 1-4 for nine 5-wk cycles
    T: 50 mg daily until relapse
    38Not reachedNot reached2346
    • CR indicates complete response; PFS, progression-free survival; OS, overall survival; AE, adverse event; MPR-R, melphalan, prednisone, and lenalidomide followed by lenalidomide maintenance; NA, not available; Rd, lenalidomide plus low-dose dexamethasone; VMP, bortezomib, melphalan, and prednisone; and VMPT, bortezomib, melphalan, prednisone, and thalidomide.

    • * Both hematologic and nonhematologic AEs.

    • CR plus very good partial response (CR alone not available).

    • Event-free survival.

    • § Disease-free survival.

    • Includes both patients who received lenalidomide maintenance and those who did not.

  • Table 3

    Outcome of patients with ND disease treated with full-dose or reduced-dose regimens

    Any grade 3-4 AEs, %Discontinuation rate because of toxicity, %PFS, %OS, %
    Standard dose therapies
        VMP4791350 at 2 y68 at 3 y
        RD51522748 at 2 y78 at 2 y
    Lower dose therapies
        VMP57,655112-1746-50 at 3 y74-87 at 3 y
        Rd51351952 at 2 y88 at 2 y
    • AE indicates adverse event; PFS, progression-free survival; OS, overall survival; RD lenalidomide plus high-dose dexamethasone; and Rd, lenalidomide plus low-dose dexamethasone.

  • Table 4