Table 2.
Safety results of acalabrutinib and zanubrutinib and direct comparisons with ibrutinib in clinical trials.
| Reference | Schedule | N of pts (Tx Status) | G ≥ 3 AEs (%) | Tox-Related Discontinuations (%) | Tox-Related Reductions (%) | Any Grade AF %, (G ≥ 3) | Any Grade Bleeding (G ≥ 3) % |
Any Grade Hypertension (G ≥ 3) % |
m Time on tx |
|---|---|---|---|---|---|---|---|---|---|
|
Byrd et al. 2020 [22] |
Acala 100 to 400 mg/d | 134 (R/R) | 66 | 13 | 4 | 7 (3) | (5) | 17.9 (7.5) | 41 |
|
Byrd et al. 2021 [23] |
Acala 100 mg bid or 200 mg/d | 99 (TN) | 35.4 (occurring in >15% of pts) | 6.1 | NR | 5 (2) | 66 (3) | 22 (11) | 41.5 |
|
Woyach et al. 2020 [25] |
Obi: C1: 100 mg D1, 900 mg D2, 1000 mg D8, D15; C2–6: 1000 mg D1 Acala: 100 mg bid |
19 (TN) 26 (R/R) |
62 77 |
5.3 15.4 |
2 pts 1 pt |
2 (2) | 71 (4) | 40 (7) | NR |
|
Sharman et al. 2022 [27,28] |
Acala: 100 mg bid | 179 (TN) | 25 events (occurring in ≥30%) + 86 events of special interest |
12.3 (at 45.7 mo) |
NR | 7.3 (1.1) | 43.6 (3.6) | 8.9 (3.9) | 58.1 |
|
Sharman et al. 2022 [27,28] |
Obi: C1: 100 mg D1, 900 mg D2, 1000 mg D8, D15; C2–6: 1000 mg D1 Acala: 100 mg bid |
179 (TN) | 76 events (occurring in ≥30%) + 98 events of special interest |
12.8 (at 46.6 mo) |
NR | 6.2 (1.1) | 49.4 (4.5) | 9.6 (4.5) | 58 |
|
Ghia et al. 2022 [26] |
Acala: 100 mg bid | 155 (R/R) | 68 | 23 | 6 | 8 (1) | 31 (3) | 8 (5) | 44.2 |
|
Byrd et al. 2021 [29] |
Acala: 100 mg bid Ibrutinib:420 mg/d |
268 (R/R) 265 (R/R) |
68.8 74.9 |
14.7 21.3 |
13.2 15.2 |
9 (4.5) 15.6 (3.4) |
38 (3.8) 51.3 (4.6) |
8.6 (4.1) 22.8 (8.7) |
38.3 35.5 |
|
Rogers et al. 2021 [44] |
Acala: 100 mg bid | 60 (R/R) | 129 events | 17 | 6.7 | 3.3 (0) | 8.3 | 13.3 (3.3) | 32 |
| Cull et al. 2021 [36] | Zanu 160 mg bid or 320 mg/d or 160 mg/d | 22 (TN) 101 (R/R) |
73.2 | 9.8 | 8.9 (at least once) |
4.9 (3.3) | 38.2 (3.3) | 19.5 (8.9) | 43 |
| Tam et al. 2022 (Group A) [39] | Zanu 160 mg bid | 241 (TN) | 53 | 8 | 14 | 3 | 41 (3.7) | 6 (6) | 26.4 (m safety FU) |
| Tam et al. 2022 (Group C) [39,41] | Zanu 160 mg bid | 111(TN) | 55 | 5 | 10 | 46 (5) | 5 (5) | 30 (m safety FU) |
|
|
Brown et al. 2022 [40] |
Zanu 160 mg bid Ibrutinib:420 mg/d |
327 (R/R) 325 (R/R) |
67.3 70.4 |
16.2 22.2 |
12.3 17 |
6.2 (2.5) 13.3 (4) |
42.3 (3.4) 41.4 (3.7) |
23.5 (15.1) 22.8 (13.6) |
28.4 24.3 |
Tx: treatment; G: grade; AEs: adverse events; Tox: toxicity; AF; atrial fibrillation; FU: follow-up; mo: months; pts: patients; NR: not reported; bid: twice daily; d: daily; Obi: Obinutuzumab; C: cycle; D: day; TN: treatment naïve; R/R: relapsed/refractory; m: median.