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Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma

Shaji K. Kumar, Betsy LaPlant, Wee Joo Chng, Jeffrey Zonder, Natalie Callander, Rafael Fonseca, Briant Fruth, Vivek Roy, Charles Erlichman and A. Keith Stewart for the Mayo Phase 2 Consortium

Article Figures & Data

Figures

  • Figure 1

    The distribution of all adverse events seen in the trial, which were considered at least possibly related to the study drug administration and seen in ≥2 patients across the study.

  • Figure 2

    Monoclonal protein response to treatment with dinaciclib. (A) Waterfall plot of the serum M protein responses among patients with a measurable M protein on serum protein electrophoresis at study entry. (B) Waterfall plot limited to patients with 24-hour urine M spike as measurable disease at study entry.

Tables

  • Table 1

    Baseline patient characteristics

    30 mg/m2 (N = 4)40 mg/m2 (N = 6)50 mg/m2 (N = 6)Original 50 mg/m2 (N = 2)Phase 2 (50 mg/m2) (N = 9)Total (N = 27)
    Age
     Median (range)70.0 (57.0-76.0)62.5 (49.0-69.0)61.5 (59.0-75.0)72.5 (70.0-75.0)70.0 (57.0-76.0)66.0 (49.0-81.0)
    Gender
     Female1 (25.0%)4 (66.7%)3 (50.0%)0 (0.0%)1 (25.0%)13 (48.1%)
     Male3 (75.0%)2 (33.3%)3 (50.0%)2 (100.0%)3 (75.0%)14 (51.9%)
    Months from diagnosis to registration
     Median (range)31.9 (20.9-47.1)43.8 (10.1-67.9)66.7 (6.7-134.3)113.6 (20.1-207.1)31.9 (20.9-47.1)41.6 (6.7-207.1)
    International staging
     Stage 10 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)1 (11.1%)1 (3.7%)
     Stage 23 (75.0%)2 (33.3%)3 (50.0%)1 (50.0%)2 (22.2%)11 (40.7%)
     Stage 31 (25.0%)4 (66.7%)3 (50.0%)1 (50.0%)6 (66.7%)15 (55.6%)
    Prior exposure
     Lenalidomide2 (50.0%)6 (100.0%)4 (66.7%)1 (50.0%)6 (66.7%)19 (70.4%)
     Bortezomib3 (75.0%)5 (83.3%)6 (100.0%)2 (100.0%)8 (88.9%)24 (88.9%)
    Metaphase cytogenetics
     Normal2 (50.0%)2 (33.3%)2 (33.3%)1 (50.0%)3 (33.3%)10 (37.0%)
     Abnormal2 (50.0%)3 (50.0%)4 (66.7%)1 (50.0%)5 (55.6%)15 (55.6%)
     Not done0 (0.0%)1 (16.7%)0 (0.0%)0 (0.0%)1 (11.1%)2 (7.4%)
    FISH result
     13q-222039
     17p-111025
     t(11;14)221016
     t(4;14)101002
     t(14;16)000112
  • Table 2

    Frequency of adverse events seen at the Phase 2 dose of 50 mg/m2, considered at least possibly related to treatment and seen in ≥2 patients

    ToxicityGrade
    1234All
    N%N%N%N%N%
    Thrombocytopenia426.7426.716.7960.0
    Leukopenia213.316.716.7426.7
    Neutropenia16.716.716.716.7426.7
    Lymphopenia426.7426.7
    Diarrhea960.0213.316.716.71386.7
    Nausea640.0213.3853.3
    Vomiting426.716.7533.3
    Fatigue533.3426.716.71066.7
    Aspartate aminotransferase increased320.0320.0
    Alanine aminotransferase increased213.3213.3
    Peripheral sensory neuropathy213.3213.3
    Vision blurred16.716.7213.3
    Hypotension213.3213.3
    Pruritus213.3213.3
    Dry eye syndrome16.716.7
  • Table 3

    Response to therapy

    Response category30 mg/m2 (N = 4)40 mg/m2 (N = 6)All 50 mg/m2 (N = 17)All (N = 27)
    VGPR1102
    PR0101
    MR0022
    SD14813
    PD2068
    NA0011