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Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma

Ajai Chari, Joaquín Martinez-Lopez, María-Victoria Mateos, Joan Bladé, Lotfi Benboubker, Albert Oriol, Bertrand Arnulf, Paula Rodriguez-Otero, Luis Pineiro, Andrzej Jakubowiak, Carla de Boer, Jianping Wang, Pamela L. Clemens, Jon Ukropec, Jordan Schecter, Sagar Lonial and Philippe Moreau

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Tables

  • Table 1.

    Baseline characteristics and prior treatment history

    CharacteristicAll treated (N = 85)Lenalidomide refractory (n = 51)
    Age, median (range), y66 (38-85)66 (38-85)
    ECOG performance status
     0-178 (92)47 (92)
     27 (8)4 (8)
    No. of prior lines
     Median (range)2 (1-4)2 (1-4)
     120 (24)6 (12)
     240 (47)26 (51)
     323 (27)18 (35)
     >32 (2)1 (2)
    Prior ASCT62 (73)33 (65)
    Prior bortezomib85 (100)51 (100)
    Prior IMiD85 (100)51 (100)
     Lenalidomide81 (95)51 (100)
     Pomalidomide13 (15)9 (18)
     Thalidomide21 (25)11 (22)
    Refractory to:*
     Lenalidomide51 (60)51 (100)
     Pomalidomide11 (13)9 (18)
     Bortezomib26 (31)21 (41)
     PI + IMiD25 (29)22 (43)
    • Unless otherwise noted, all data are n (%).

    • * Refractoriness was based on most recent prior medication.

  • Table 2.

    Daratumumab serum concentrations with single vs split first dose in the all treated population

    Postfirst doseC3 D1 preinfusionC3 D1 end of infusion
    C1 D1 end of infusionC1 D2 end of infusion
    Single first dose
     Patients, n899
     Mean daratumumab serum concentration, μg/mL (SD)321.14 (49.0)517.46 (137.2)895.61 (169.5)
     CV, %15.326.518.9
     Geometric mean daratumumab serum concentration, μg/mL317.73502.54882.53
    Split first dose
     Patients, n695252
     Mean daratumumab serum concentration, μg/mL (SD)255.03 (71.87)618.53 (256.2)951.44 (350.1)
     CV, %28.241.436.8
     Geometric mean daratumumab serum concentration, μg/mL244.90549.57855.74
    • C, cycle; CV, coefficient of variation; D, day; SD, standard deviation.

  • Table 3.

    Most common (>10%) TEAEs

    Any gradeGrade 3/4
    Total TEAEs85 (100)65 (77)
     Thrombocytopenia57 (67)26 (31)
     Anemia43 (51)18 (21)
     Nausea35 (41)1 (1)
     Upper respiratory tract infection35 (41)1 (1)
     Asthenia34 (40)10 (12)
     Vomiting34 (40)1 (1)
     Pyrexia30 (35)1 (1)
     Diarrhea29 (34)2 (2)
     Dyspnea29 (34)3 (4)
     Insomnia27 (32)4 (5)
     Neutropenia26 (31)18 (21)
     Hypertension24 (28)15 (18)
     Lymphopenia23 (27)20 (24)
     Cough22 (26)0
     Headache21 (25)1 (1)
     Back pain20 (24)0
     Bronchitis14 (17)0
     Fatigue13 (15)3 (4)
     Nasopharyngitis13 (15)0
     Respiratory tract infection13 (15)0
     Constipation12 (14)0
     Gastroenteritis12 (14)0
     Peripheral edema12 (14)0
     Influenza11 (13)3 (4)
     Muscle spasms11 (13)0
     Pain in extremity10 (12)0
     Musculoskeletal chest pain9 (11)0
    • All data are n (%). N = 85.

  • Table 4.

    IRRs during all infusions

    Single first dose (n = 10)Split first dose (n = 75)
    First infusionSecond infusionSubsequent infusionsTotalFirst infusionSecond infusionSubsequent infusionsTotal
    Total patients with IRR5 (50)2 (20)1 (10)6 (60)28 (37)1 (1)6 (8)32 (43)
    Patients with an IRR
     Allergic rhinitis00006 (8)006 (8)
     Throat irritation1 (10)1 (10)01 (10)4 (4)01 (1)3 (4)
     Cough00002 (3)002 (3)
     Dyspnea00003 (4)003 (4)
     Nasal congestions00002 (3)2 (3)00
     Wheezing00001 (1)001 (3)
     Vomiting2 (20)002 (20)5 (7)01 (1)6 (8)
     Nausea3 (30)2 (20)04 (40)1 (1)1 (1)1 (1)3 (4)
     Abdominal discomfort00001 (1)001 (1)
     Pyrexia01 (10)01 (10)1 (1)2 (3)03 (4)
     Chills00002 (3)002 (3)
     Administration site inflammation00001 (1)001 (1)
     Feeling cold00001 (1)001 (1)
     Hyperthermia00001 (1)001 (1)
     Flushing00002 (3)1 (1)03 (4)
     Hypertension1 (10)002 (20)2 (3)002 (3)
     Hot flush00002 (3)002 (3)
     Hypotension00001 (1)001 (1)
     Tachycardia001 (10)1 (10)001 (1)1 (1)
     Sinus tachycardia00001 (1)001 (1)
     Erythema1 (10)01 (10)1 (10)1 (1)001 (1)
     Hyperhidrosis001 (10)1 (10)01 (1)01 (1)
     Pruritus00001 (1)001 (1)
     Rash00001 (1)001 (1)
     Urticaria00001 (1)001 (1)
     Dizziness00001 (1)001 (1)
     Back pain00001 (1)001 (1)
     Eyelid edema00001 (1)001 (1)
     Nervousness1 (10)01 (10)1 (10)0000
    • All data are n (%).

  • Table 5.

    ORR and MRD based on prior treatment history

    SubgroupORR*MRD-negative rate (10−5)
    Patients in group, n % Patients in group, n %
    All response evaluable8284 1136
    Refractory to lenalidomide4879520
    Lenalidomide exposed but not refractory3090450
    Refractory to bortezomib2584268
    Refractory to IMiD5377520
    IMiD exposed but not refractory2997650
    Refractory to PI and IMiD248320
    Cytogenetic risk
     High§1369367
     Standard5290633
    • * Data are based on a computerized algorithm.

    • Of the 27 patients who achieved CR or better, 11 received MRD testing.

    • Biomarker risk-evaluable population.

    • § Includes patients who have del17p, t(14;16), t(4;14) or a combination of these by fluorescence in situ hybridization or karyotype.