Table 3.
Summary of treatment exposure and overall safety profile of ixazomib-Rd and placebo-Rd
| Variable | Ixazomib-Rd (n = 57) | Placebo-Rd (n = 58) |
|---|---|---|
| Median number of cycles, n (range) | 9 (1–25) | 6.5 (1–25) |
| Patients receiving ≥10 cycles, n (%) | 28 (49) | 20 (34) |
| Median treatment duration, days (range) | 272 (8–679) | 181 (16–712) |
| Relative dose intensity, %, mean (standard deviation)/median (range)a | ||
| Ixazomib or placebo | 96.0 (8.13)/100 (67–100) | 98.7 (2.95)/100 (89–100) |
| Lenalidomide | 89.7 (15.96)/97.1 (38–100) | 94.5 (14.87)/99.8 (53–137) |
| Dexamethasone | 91.7 (13.52)/97.5 (50–100) | 95.2 (9.80)/98.2 (45–100) |
| Rates of AEs, n (%) | ||
| Any AE | 57 (100) | 57 (98) |
| Any drug-related AE | 54 (95) | 57 (98) |
| Any grade ≥3 AE | 38 (67) | 43 (74) |
| Any drug-related grade ≥3 AE | 33 (58) | 37 (64) |
| Any serious AE (SAE) | 19 (33) | 18 (31) |
| Any drug-related SAE | 11 (19) | 7 (12) |
| AEs resulting in dose reduction of any study drug | 12 (21) | 11 (19) |
| Ixazomib/placebob | 1 (2) | 0 |
| Lenalidomidec | 7 (12) | 9 (16) |
| Dexamethasoned | 5 (9) | 3 (5) |
| AEs resulting in discontinuation of any study druge | 8 (14) | 8 (14) |
| AEs resulting in discontinuation of study regimen | 5 (9) | 6 (10) |
| On-study deathsf | 4 (7) | 5 (9) |
aRelative dose intensity defined as total amount of dose taken divided by total prescribed dose across treated cycles, as a percentage
bIxazomib dose reduction required due to peripheral neuropathy and herpes zoster
cLenalidomide dose reductions on the ixazomib-Rd arm associated with AEs of leukopenia, neutropenia, fatigue, pneumonia, glomerular filtration rate decreased, platelet count decreased, peripheral neuropathy, and acute kidney injury (dose reduction associated with >1 AE in some patients). Lenalidomide dose reductions on the placebo-Rd arm associated with AEs of granulocytopenia, pancytopenia, glomerular filtration rate decreased, neutrophil count decreased, musculoskeletal pain, acute kidney injury, chronic kidney disease, renal failure, and pruritic rash. One patient on each arm required two lenalidomide dose reductions
dDexamethasone dose reductions on the ixazomib-Rd arm associated with AEs of diarrhea, face edema, peripheral edema, bronchitis, herpes zoster, lung infection, diabetes mellitus, peripheral neuropathy, and chronic kidney disease (dose reduction associated with >1 AE in some patients). One patient on the ixazomib-Rd arm required two dexamethasone dose reductions. Dexamethasone dose reductions on the placebo-Rd arm associated with AEs of pancytopenia, cataract, asthenia, and malaise (dose reduction associated with >1 AE in some patients)
eOnly osteolysis (3 patients on the ixazomib-Rd arm), pneumonia (2 patients on the ixazomib-Rd arm), and lung infection (2 patients on the placebo-Rd arm) were reported in >1 patient
fDefined as deaths during treatment or within 30 days after the last dose of any study drug