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Efficacy and predictors of response of lenalidomide and rituximab in patients with treatment-naive and relapsed CLL

Paolo Strati, Koichi Takahashi, Christine B. Peterson, Michael J. Keating, Philip A. Thompson, Naval G. Daver, Nitin Jain, Jan A. Burger, Zeev Estrov, Susan M. O'Brien, Hagop M. Kantarjian, William G. Wierda, P. Andrew Futreal and Alessandra Ferrajoli

Article Figures & Data

Figures

  • Figure 1.

    Gene mutation distribution according to treatment arm. No difference in the frequency of gene mutations and mutated pathway groups before initiation of the study treatment was observed when comparing TN patients vs R patients. NOTCH signaling pathway: NOTCH1, SPEN, FBXW7; inflammatory/B-cell receptor pathway: BIRC3, EGR2, NFKBIE, KRAS, SAMHD1, BRAF; WNT signaling pathway: MGA, MED12, FBXW7; DNA damage and cell cycle control pathway: TP53, ATM, POT1, BRCC3, RB1; chromatin modification pathway: ZMYM3, IKZF3, ASXL1, CREBBP, SP140, KM2TC; and RNA and ribosomal processing pathway: SF3B1, XPO1.

  • Figure 2.

    Survival according to treatment arm. (A) PFS according to treatment arm. (B) OS according to treatment arm. mPFS, median PFS.

Tables

  • Table 1.

    Patients’ baseline characteristics

    CharacteristicTN (n = 61)R (n = 59)
    Age, y66 (42-79)63 (41-84)
    Sex
     Male42 (69)43 (73)
     Female19 (31)16 (27)
    Rai stage
     0-II35 (57)29 (49)
     III-IV26 (43)30 (51)
    White blood cell count, ×109/L76 (9-232)28 (2-189)
    Absolute lymphocyte count, ×109/L68 (2-197)26 (0-177)
    Absolute neutrophil count, ×109/L4 (0-18)3 (0-9)
    Hemoglobin level, g/dL12.3 (8.9-15.9)12.5 (8.6-16.4)
    Platelet count, ×109/L141 (45-325)115 (32-267)
    B2M level, mg/L3.8 (1.4-10.5)4 (1.5-18.3)
    eGFR, mL/min73 (42-127)70 (36-118)
    IgHV gene status
     Mutated18 (37)8 (17)
     Unmutated31 (63)39 (83)
     No product/missing1212
    FISH
     Del13q20 (33)15 (31)
     Normal8 (13)8 (16)
     +1213 (22)7 (14)
     Del11q15 (25)13 (27)
     Del17p4 (7)6 (12)
     Missing110
    Karyotype
     Noncomplex42 (82)22 (63)
     Complex9 (18)13 (37)
     Missing1024
    No. of previous treatmentsn/a2 (1-9)
    Fludarabine refractoryn/a10 (17)
    • Data are presented as median (range) or no. (%).

    • eGFR, estimated glomerular filtration rate; IgHV, immunoglobulin heavy chain variable region; n/a, not applicable.

  • Table 2.

    Response to therapy

    MeasureNo. (%)
    TN (n = 55)R (n = 53)
    Overall response40 (73)34 (64)
    Complete response19 (35)15 (28)
    Negative measurable residual disease9 (16)1 (2)
    Nodular partial remission14 (26)5 (9)
    Partial response7 (12)14 (25)
  • Table 3.

    Frequency of grade 3/4 toxic effects

    Toxic effectNo. (%)
    TN (n = 61)R (n = 59)
    Neutropenia29 (47)35 (59)
    Anemia8 (13)0 (0)
    Thrombocytopenia7 (11)10 (17)
    Infectious toxic effect5 (10)11 (22)
    Cardiovascular toxic effect3 (6)3 (6)
    Skin toxic effect3 (6)0 (0)
    Metabolic toxic effect1 (2)0 (0)
    Musculoskeletal toxic effect2 (4)0 (0)