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How I treat myeloma with new agents

Philippe Moreau

Article Figures & Data

Tables

  • Table 1.

    Major treatment regimens in MM

    RegimenUsual dosing schedule
    Frontline
     VMPBortezomib: 1.3 mg/m2 IV, days 1, 8, 15, 22; melphalan: 9 mg/m2 oral, days 1-4; prednisone: 60 mg/m2 oral, days 1-4; repeated every 35 d
     RdLenalidomide: 25 mg oral days 1-21 every 28 d; dexamethasone: 40 mg oral days 1, 8, 15, 22 every 28 d; repeated every 4 wk
     MPTMelphalan: 0.25 mg/kg oral, days 1-4 (use 0.20 mg/kg per day oral, days 1-4 in patients >75 y of age); prednisone: 2 mg/kg oral, days 1-4; thalidomide 100-200 mg oral, days 1-28 (use 100-mg dose in patients >75 y of age); repeated every 6 wk
     VCDCyclophosphamide: 300 mg/m2 orally on days 1, 8, 15 and 22; bortezomib 1.3 mg/m2 intravenously on days 1, 8, 15, 22; dexamethasone 40 mg orally on days 1, 8, 15, 22; repeated every 4 wk
     VTDBortezomib: 1.3 mg/m2 IV, days 1, 8, 15, 22; thalidomide: 100-200 mg oral, days 1-21; dexamethasone: 20 mg on day of and day after bortezomib (or 40 mg on days 1, 8, 15, 22); repeated every 4 wk × 4 cycles as pretransplant induction therapy
     VRdBortezomib: 1.3 mg/m2 IV days 1, 8, 15; lenalidomide: 25 mg oral, days 1-14; dexamethasone: 20 mg on day of and day after bortezomib (or 40 mg on days 1, 8, 15, 22); repeated every 3 wk
    Relapsed/refractory disease
     KRdCarfilzomib 20 mg/m2 (cycle 1) and 27 mg/m2 (subsequent cycles) intravenously on days 1, 2, 8, 9, 15, 16; lenalidomide 25 mg oral days 1 to 21; dexamethasone 20 mg on day of and day after bortezomib (or 40 mg days 1, 8, 15, 22); repeated every 4 wk
     VD-PanoBortezomib: 1.3 mg/m2 IV, days 1, 8, 15, 22; dexamethasone: 20 mg on day of and day after bortezomib; panobinostat: 20 mg oral, days 1, 3, 5, wk 1 and 2; repeated every 3 wk (cycles 1-8)
     KdCarfilzomib: 56 mg/m2 IV, days 1, 2, 8, 9, 15, 16 (20 mg/m2 d 1, 2, cycle 1 only); dexamethasone: 20 mg, days 1, 2, 8, 9, 15, 16, 22, 23; 28-d cycles
     Rd-EloLenalidomide: 25 mg oral, days 1-21; dexamethasone: 40 mg/wk; elotuzumab: 10 mg/kg IV per week cycle 1 and 2, every other week cycles 3+; repeated every 28 d
     IRdLenalidomide: 25 mg oral, days 1-21; dexamethasone: oral 40 mg, days 1, 8, 15, 22; ixazomib: 4 mg oral, days 1, 8, 15; repeated every 28 d
     DVdBortezomib: 1.3 mg/m2 subcutaneous, days 1, 4, 8, 11 (cycles 1-8); dexamethasone: 20 mg oral, days 1, 2, 4, 5, 8, 9, 11, 12 (cycles 1-8); daratumumab: 16 mg/kg IV every week (cycles 1-3), every 3 wk (cycles 4-8), every 4 wk (cycles 9+); cycles 1-8: repeated every 21 d; cycles 9+: repeated every 28 d
     DRdLenalidomide: 25 mg oral, days 1-21; dexamethasone: 40 mg oral, every week; daratumumab 16 mg/kg IV every week (cycles 1-2), every other week (cycles 3-6), q4w cycles 7+; cycles: 28 d
    • q4w, every 4 weeks; Rd-Elo, lenalidomide/dexamethasone/elotuzuman; VD-pano, bortezomib/dexamethasone/panobinostat; VTD, bortezomib/thalidomide/dexamethasone.

  • Table 2.

    Phase III trials in relapsed and/or refractory MM: efficacy

    Study (reference)RegimensPatients, nPrior therapies, median, n (range)Experimental vs placebo arm
    ORR, %≥VGPR, %PFS, mo (HR)
    Lenalidomide-based regimens
     ASPIRE (25)Rd ± carfilzomib7922 (1-3)87 vs 6770 vs 4026 vs 18 (0.69)
     TOURMALINE-MM1 (28)Rd ± ixazomib7221 (1-3)78 vs 7248 vs 3920.6 vs 14.7 (0.74)
     ELOQUENT 2 (27)Rd ± elotuzumab6462 (1-3)79 vs 6633 vs 2819.4 vs 14.9 (0.70)
     POLLUX (29)Rd ± daratumumab5691 (1-11)93 vs 7676 vs 44Not reached vs 18.4 (0.37)
    Bortezomib-based regimens
     PANORAMA 1 (34)Vd ± panobinostat7681 (1-3)61 vs 55Not mentioned12 vs 8 (0.63)
     CASTOR (33)Vd ± daratumumab4982 (1->3)83 vs 6359 vs 29Not reached vs 7.16 (0.39)
     Randomized phase II study (35)Vd ± elotuzumab1501 (1-3)66 vs 6337 vs 279.7 vs 6.9 (0.72)
     ENDEAVOR (31)Kd vs Vd9291 (1-3)77 vs 6354 vs 2918.7 vs 9.4 (0.53)
    • ORR, overall response rate.

  • Table 3.

    Phase 3 trials in relapsed and/or refractory MM: convenience

    Regimen (reference)Route of administrationDosing scheduleHospital/clinic visitAdministration time
    KRd (25)IVCycle 1-12: days 1, 2, 8, 9, 15, and 16 of 28-d cycle. Cycle 13-18: days 1, 2, 15, and 16 of 28-d cycle2/wk (3 wk on/1 wk off)>30 min + pretreatment hydration
    IRd (28)PODays 1, 8, and 15 of 28-d cycleEvery 4 wk0 h
    Rd + elotuzumab (27)IVDays 1, 8, 15, and 22 of 28-d cycle (cycles 1 and 2), then days 1 and 15 (cycle 3+)1/wk for 8 wk, then every 2 wk5 h; need premedication
    DRd (29)IVDays 1, 8, 15m and 22 of 28-d cycle (cycle 1 and 2), days 1 and 15 (cycle 3-6), then every 4 wk thereafter1/wk for 8 wk, every 2 wk for 16 wk, then every 4 wk6.5 h for the first infusion and 3.5 h for subsequent infusions; need premedication
    Vd + panobinostat (34)PO (+ bortezomib IV)Panobinostat: days 1, 3, 4, 8, 10, and 12 of 21-d cycle; bortezomib: days 1, 4, 8, and 112/wk (2 wk on/1 wk off)∼1 h for bortezomib
    DVd (33)IV (+ bortezomib SC)Daratumumab: days 1, 8, and 15 of 21-d cycle (cycle 1-3), every 3 wk (cycle 4-8), then every 4 wk; bortezomib: days 1, 4, 8, and 114-5 visits by 21-d cycle6.5 h for the first infusion and 3.5 h for subsequent infusions; need premedication
    Kd (31)IVCarfilzomib: days 1, 2, 8, 9, 15, and 16 of 28-d cycle2/wk (3 wk on/1 wk off)>30 min + pretreatment hydration
    • PO, per os; SC, subcutaneous.