Table 1.
Associated toxicities and treatment outcomes reported with BTK inhibitors.
| Acalabrutinib | Ibrutinib | |||||||
|---|---|---|---|---|---|---|---|---|
| R/R MCL (23, 24) | R/R CLL (22) | TN & R/R WM a (25, 26) | TN CLL (21) | R/R MCL (9) | R/R CLL (end of trial/long-term follow-up) (27, 28) | R/R WM (29) a | TN CLL (end of trial/long-term follow-up) (12, 30) | |
| Number of patients | 124 | 155 | 106 | 179/179 b | 111 | 195/195 | 63 | 136/136 |
| Median duration of treatment (range), months | 17.3 (0.1–35.1) | 15.7 (1.1–22.4) | N/A | 27.7 (IQR 25.0–32.8)/(IQR 24.8–33.0) | N/A | 8.6 (0.2–16.1)/41.0 (0.2–71.1) | 19.1 (0.5–29.7) | 17.4 (0.7–24.7)/57.1 (0.7–66.0) |
| Median duration of follow-up (range), months | 26.3 (0.3–35.1) | 16.1 (0.03–22.4) | 27.4 (IQR 26.0–29.7) | 28.3 (IQR 25.6–33.1) | 15.3 (1.9–22.3) | 9.4 (0.1–16.6)/65.3 (0.3–71.6) | N/A | 18.4/60 (0.1–66) |
| Adverse events (all grades unless otherwise stated) | ||||||||
| Headache | 38% | 22% | 39% | 40%/37% | N/A (<15%) | N/A/21% c | 2% | N/A/N/A |
| Nausea | 19% | 7% | 23% | 20%/22% | 31% | G1 24%, G2 6%, G3 2%/36% c | N/A | 22%/26% |
| Diarrhea | 36% | 18% | 33% | 39%/35% | 50% | G1 27%, G2 10%, G3 4%/62% c | 3% | 42%/50% |
| Fatigue | 28% | 10% | 22% | 28%/18% | 41% | G1 18%, G2 12%, G3 3%/42% c | N/A | 30%/36% |
| Peripheral edema | N/A | N/A | N/A | 12%/9% | 28% | N/A/24% b | N/A | 19%/27% |
| Myalgia | 21% | N/A | N/A | N/A | N/A (<15%) | N/A/N/A | N/A | N/A/N/A |
| Neutropenia | 10% | 19% | 17% | 32%/11% | 18% | G3 18%/31% c | 22% | 16%/13% d |
| Bleeding events | 33% | 26% | 58% | 43%/39% | N/A | N/A/N/A | 6% | N/A/N/A |
| Grade ≥3 | 2% | 1% | 3% | 2%/2% | 5% | N/A/N/A | N/A | N/A/N/A |
| Cardiac events (all) | 10% | N/A | N/A | N/A | N/A | N/A/N/A | N/A | N/A/N/A |
| Atrial fibrillation | 0 | 5% | 5% | 3%/4% | N/A | 7%/12% | 5% | 6%/16% |
| Hypertension | 3% | 3% | N/A | 3%/2% b | N/A | N/A/21% | 5% | 4% b /26% |
| Infections (all) | 53% | N/A | N/A | N/A | N/A | N/A/N/A | N/A | N/A/N/A |
| Grade ≥3 | 15% | 15% | 21%/14% | 25% | N/A/45% | N/A | N/A/N/A | |
| Discontinuation due to adverse events | 8% | 11% | 7% | 11%/9% | 7% | 7%/16% | 10% | 9%/28% |
| Treatment outcomes | ||||||||
| Median progression-free survival (95% CI, when available), months | 20 (16.5–27.7) | NR | TN NR, R/R NR | NR/NR | 13.9 (7.0–NR) | NR/44.1 (38.5–56.2) | N/A | NR/NR |
| Progression-free survival rate (95% CI, when available) | 2-year: 49.0% (39.6–57.8) | 12-month: 88% (81–92) | 2-year: TN 90% (47–99), R/R 82% (72–89) | 2-year: 93% (87–96)/87% (81–92) | N/A | 6-month: 88%/60-month: 40% | 2-year: 69.1% (53.2–80.5) | 18-month: 90%/5-year: 70% |
| Median overall survival (95% CI, when available), months | NR | NR | TN NR, R/R NR | NR/NR | NR | NR/67.7 (61.0–NE) | N/A | NR/NR |
| Estimated overall survival rate (95% CI, when available) | 2-year: 72.4% (63.5–79.5) | 12-month: 94% (89–97) | 2-year: TN 92% (54–99), R/R 89% (80–94) | 2-year: 95% (91–97)/95% (90–97) | 18-month: 58% | 12-month: 90%/N/A | 2-year: 95.2% (86.0–98.4) | 2-year: 98%/5-year: 83% |
| Overall response rate | 81% | 81% | TN 93%, R/R 93% | 94%/86% | 68% | 42.6%/91% | 90.5% | 86%/92% |
BTK, Bruton tyrosine kinase; CI, confidence interval; CLL, chronic lymphocytic leukemia; G, grade; MCL, mantle cell lymphoma; N/A, not available; NE, not evaluable; NR, not reached; R/R, relapsed/refractory; TN, treatment-naïve; WM, Waldenstrom’s macroglobulinemia.
Data are percentages of patients who reported the adverse event, unless stated otherwise.
Please note that there are no head-to-head trials comparing acalabrutinib and ibrutinib—these data come from separate trials, in which patient characteristics differed, so they cannot be compared directly. Data are taken from treatment arms in which acalabrutinib or ibrutinib were given as monotherapy.
Please note the differences in the trial designs and reporting for the two WM studies: The acalabrutinib trial included both TN and R/R patients with a primary endpoint of ORR and reported all AEs of any grade (regardless of causality), whereas the ibrutinib trial was in R/R patients with a primary endpoint of ORR, and only reported adverse events reported of grade 2–4 that were deemed possibly, probably, or definitely associated with study treatment are reported.
Data are acalabrutinib plus obinutuzumab/acalabrutinib monotherapy.
Data estimated from Munir et al., 2019 (28) Figure S6.
Events grade ≥3 only reported.