Table 4.
Major clinical trials and real-world studies based on ixazomib.
| Setting | Study | Age* | Median lines (range)/prior exposure | Response(ORR/≥VGPR/≥CR) | PFS/OS/DOT | Toxicity, G≥3 |
|---|---|---|---|---|---|---|
| MAJOR CLINICAL TRIALS | ||||||
| RRMM patients |
TOURMALINE-MM1 (11) IRd: N=360 (vs. placebo-Rd) |
66 | (1-3)/ Bort-exposed: 69% Len-exposed: 12% |
- 78%/48%/14% | mPFS: 20.6 mo OS: NR (FU: 23 mo) |
- Neutropenia 18% - Anemia 9% - Thrombocytopenia 12% - Rash 5% - Neuropathy 2% - Diarrhea 6% (any G 51%) - Nausea 2% (any G 31%) - Discontinuation 17% |
| First line |
TOURMALINE-MM2 (65) IRd: N=351 (vs. placebo-Rd: N=354) |
73-74 | – | IRd: - 82%/63%/26% Placebo-Rd: - 80%/48%/14% |
IRd vs. placebo-Rd: -mPFS: 35 vs. 21 mo - OS: NR vs. 52 mo |
- AEs 88% vs. 81% |
|
Maintenance,
TE patients |
TOURMALINE-MM3** (66) I: N=395 (vs. placebo: N=261) |
58 | PI-exposed: 59% IMiD-exposed: 11% PI+IMiD-exposed: 30% |
– | mPFS: 23 mo mOS: NA |
- Neutropenia 5% - Anemia 4% - Thrombocytopenia 5% - Rash 2% - Pneumonia 7% - Diarrhea 3% |
|
Maintenance,
NTE patients |
TOURMALINE-MM4** (67) I: N=425 (vs. placebo: N=281) |
73 | PI-exposed: 83% IMiD-exposed: 32% PI+IMiD-exposed: 15% |
– | mPFS: 17.4 mo | - Neutropenia 2% - Thrombocytopenia 2% - Infection 6% |
| MAJOR REAL-WORLD STUDIES | ||||||
| RRMM patients |
Terpos et al., 2020 (62) IRd: N=155 |
68 | 1 (1-7)/ Bort-exposed: 91% Carf-exposed: 91% Len-exposed: 17% |
- 74%/35%/16% | mPFS: 27 mo mOS: NA |
- Neuropathy 3% (any G 35%) - Pneumonia 8% - Discontinuation 9% |
| RRMM patients |
Cohen et al., 2020 (63) Ixa-based regimens: N=78 (IRd: 82%) |
68 | 1 (1-6)/ Bort-exposed: 87% Carf-exposed: 5% Len-exposed: 26% |
- 88%/49%/9% | mPFS: 24 mo mOS: NR |
- Neutropenia 6% - Thrombocytopenia 5% - Anemia 6% - Diarrhea 3% - Neuropathy 3% (any G 17%) - Rash 4% - Pneumonia 3% - Discontinuation 11% |
| RRMM patients |
Hungarian Ixazomib Named Patient Program, Varga et al., 2019 (64) IRd: N=77 |
68 | 2 (1–3)/ Bort-exposed: 99% |
- 80%/22%/12% | mPFS: 11 mo mOS: NA |
- Neutropenia 8% - Anemia 5% - Thrombocytopenia 7% - Diarrhea 1% - Infection 5% |
| First line |
J. Li et al., 2020*** (68) IRd: N=38 Other Ixa-based regimens: N=47 |
67 | – | - 92%/58%/26% | mPFS: NR 1-y PFS rate: 85.5% mOS: NR 2-y OS rate: 67% |
- Neutropenia 29% - Anemia 31% - Thrombocytopenia 18% - Rash 42% - Pneumonia 13% - Diarrhea 10% |
|
Maintenance,
NTE patients |
Shen et al., 2021 (69) I: N=37**** |
63 | Bort-exposed: 100% | – | mPFS: 16 mo mOS: NA |
- Neutropenia 1% - Diarrhea 6% |
*Age: median age. **The data reported refer to the ixazomib maintenance arm. ***The data reported refer to the IRd arm, in order to perform the comparison. ****The data reported refer to NDMM NTE patients, excluding RRMM patients.
RRMM, relapsed/refractory multiple myeloma; TE, transplant-eligible; NTE, non-transplant-eligible; I, Ixa, ixazomib; R, Len, lenalidomide; d, dexamethasone; N, number; Bort, bortezomib; PI, proteasome inhibitor; IMiD, immunomodulatory drug; ORR, overall response rate; ≥VGPR, at least a very good partial response; ≥CR, at least a complete response; PFS, progression-free survival; OS, overall survival; DOT, duration of treatment; mPFS, median PFS; mOS, median OS; mo, months; y, years; NR, not reached; FU, follow-up; NA, not available; G, grade; AEs, adverse events; NDMM, newly diagnosed multiple myeloma.