Table 2.
Summary of safety with ixazomib, alone or in combination, in trials in RRMM and newly diagnosed MM
| Study | Phase | Na | Regimen | Ixazomib dose schedule | Hematologic AEs | Nonhematologic AEs |
|---|---|---|---|---|---|---|
| Single-agent ixazomib | ||||||
| C1600349 | 1 | 55/60 | Ixazomib | MTD 2 mg/m2 twice-weekly | Drug-related grade 3/4 AE (≥5%): thrombocytopenia 37%, neutropenia 17%, lymphopenia 5% | Drug-related grade 3/4 AE (≥5%): skin and SC tissue disorders 8%, fatigue 7% PN: 12% (no grade ≥3) |
| C1600448 | 2 | 50/60 | Ixazomib (weekly) | MTD 2.97 mg/m2 weekly | Drug-related grade 3/4 AE (≥5%): thrombocytopenia 33%, neutropenia 18%, lymphopenia 8%, anemia 7%, leukopenia 5% | Drug-related grade 3/4 AE (≥5%): diarrhea 17%, fatigue 8%, nausea 7%, decreased appetite 7%, vomiting 5% PN: 20% (2% grade 3) |
| Mayo Clinic phase 264 | 2 | 32/33 | Ixazomib ± dex | 5.5 mg weekly | NR | PN: 18% grade 1, 6% grade 2 (no grade ≥3) |
| Mayo Clinic phase 265 | 2 | 71 | Ixazomib | 4 mg vs 5.5 mg weekly | 15% vs 37% hematologic AEs | 6% vs 29% nonhematologic AEs; PN 55% (no grade 3) vs 43% (3% grade 3) |
| Ixazomib–Rd | ||||||
| TOURMALINE-MM1 (C16010)6 | 3 | 360 | Ixazomib–Rd vs | 4 mg weekly | Grade 3 AEs: neutropenia 18% vs 18%, thrombocytopenia 12% vs 5%, anemia 9% vs 13% | Grade 3 AEs: diarrhea 6% vs 3%, rash-related AEs 5% vs 2%, fatigue 4% vs 3%, PN 2% vs 2% |
| 362 | Placebo–Rd | Grade 4 AEs: neutropenia 5% vs 6%, thrombocytopenia 7% vs 4% | Any-grade second primary malignancies: 5% vs 4% Any-grade PN: 27% vs 22% |
|||
| C1600547 | 1/2 | 65 | Ixazomib–Rd | 4 mg weekly | Drug-related grade 3 AEs (≥5%): neutropenia 12%, thrombocytopenia 8%, lymphopenia 6%, leukopenia 5% | Drug-related grade 3 AEs (≥5%): rash 17%, fatigue 9%, diarrhea, hypokalemia, PN, vomiting each 6%, nausea, hypertension, hypophosphatemia each 5% |
| C1600860 | 1/2 | 65 | Ixazomib–Rd | 3 mg twice-weekly | Drug-related grade 3 AEs (≥5%): thrombocytopenia 6%, decreased lymphocyte count, hyponatremia, neutropenia, each 5% | Drug-related grade 3 AEs (≥5%): rash-related AEs 16%, hyperglycemia 8%, pneumonia 6%, peripheral neuropathies 5% |
| C1601357 | 1 | 43 | Ixazomib–Rd, Asian pts | 4 mg weekly | Drug-related grade 3 AEs: thrombocytopenia 14%, neutropenia 11%, anemia 6% Drug-related grade 4 AEs: thrombocytopenia 8% |
Drug-related grade 3 AEs: diarrhea 17%, fatigue 8% PN: 25% (all-grade, all cause; no grade 3/4) |
| Other combinations | ||||||
| C1600662 | 2 | 16 | Ixazomib twice-weekly + MP | 6/9 | Grade ≥3 AEs: neutropenia 33%, thrombocytopenia 22% | Grade ≥3 AEs: maculo-papular rash 22%, pruritic rash 22% |
| 6/9 | Ixazomib weekly + MP | 7/7 | Grade ≥3 AEs: neutropenia 29% | NR | ||
| C1602061 | 2 | 70 | Ixazomib–Cd (C 300 mg vs C 400 mg) | 4 mg weekly | Grade ≥3 AEs: anemia 11% vs 15%, neutropenia 14% vs 35%, thrombocytopenia 3% vs 10% | Grade ≥3 AEs: nausea 3% vs 0%, diarrhea 6% vs 0%, vomiting 3% vs 0%, constipation 3% vs 3% |
| Case Comprehensive Cancer Center75 | 1 | 11 | Ixazomib + panobinostat + dex | 4 mg weekly | Grade 3 AEs: neutropenia 2 pts, thrombocytopenia 1 pt | No grade ≥3 nonhematologic AEs |
| Alliance76 | 1 | 17 | Ixazomib + pomalidomide + dex | 3–4 mg weekly | Drug-related grade 3 AEs: neutropenia 29%, thrombocytopenia 12%, lymphopenia 29% Grade 4 AEs: neutropenia 6%, thrombocytopenia 6% |
No grade ≥3 drug-related nonhematologic AEs |
| City of Hope Medical Center | 1 | 21 | Ixazomib + pomalidomide + dex | 3–4 mg weekly | Grade ≥3 AEs: anemia 2 pts, neutropenia 6 pts, thrombocytopenia 3 pts | Grade 3 lung infection in 1 pt |
Notes:
a
Number of response-evaluable patients/total number of treated patients.
Abbreviations: AE, adverse event; CD, cyclophosphamide-dexamethasone; dex, dexamethasone; mo(s), month(s); MM, multiple myeloma; MP, melphalan–prednisone; MTD, maximum tolerated dose; NR, not reported; PN, peripheral neuropathy; pts, patients; Rd, lenalidomide-dexamethasone; RRMM, relapsed and/or refractory multiple myeloma.