Table 5.
Selected features of approved BTK inhibitors and those in later-stage clinical development
| Parameter | Ibrutinib [4, 5] | Acalabrutinib [7, 8] | Zanubrutinib [10] | Tirabrutinib [13, 17] | Orelabrutinib [28, 104] | Pirtobrutinib [20] | Nemtabrutinib [23] |
|---|---|---|---|---|---|---|---|
| Other names | Imbruvica®; PCI-32765 | Calquence®; ACP-196 | Brukinsa®; BGB-3111 | Velexbru®; ONO-4059 | 宜诺凯®; ICP 022 | LOXO-305 | MK-1026; ARQ-531 |
| Phase of developmenta | Marketed | Marketed | Marketed | Marketed | Marketed | Phase III | Phase II |
| First approval | 2013 (USA) | 2017 (USA) | 2019 (USA) | 2020 (Japan) | 2020 (China) | ||
| Approved indicationsa | CLL (USA, EU, plus several other countries); MCL (USA, EU, Japan, Mexico); MZL (USA, Canada); WM (USA, EU) | CLL (USA, EU, plus several other countries); MCL (USA, plus several other countries) | CLL (China); MCL (USA, plus several other countries); MZL (USA); WM (USA, Australia, Canada, China) | PCNSL (Japan); WM (Japan) | CLL (China); MCL (China) | ||
| Dosageb | 420 mg QD in CLL; 560 mg QD in MCL/MZL | 100 mg bid | 160 mg bid or 320 mg QD | 480 mg QD | 150 mg QD | 200 mg QD | 65 mg QD |
| Use in patients with renal impairment | |||||||
| Mild | Yes | Yes | Yes | Yes | Yes | ||
| Moderate | Yes | Yes | Yes | Yes | With caution | ||
| Severe | No data | No data | Yes | No data | With caution | ||
| ESRD | No data | No data | No data | No data | No data | ||
| Use in patients with hepatic impairment | |||||||
| Mild | Reduce dose | Yes | Yes | Yes | Yes | ||
| Moderate | Reduce dose | Yes | Yes | No data | With caution | ||
| Severe | No | No | Reduce dose | No data | No | ||
| Food effect | No | No | No | Yes | No | ||
| Most common adverse events | Thrombocytopenia, diarrhoea, fatigue, musculoskeletal pain, neutropenia, rash | Anaemia, neutropenia, URTI, thrombocytopenia, headache, diarrhoea, musculoskeletal pain | Neutropenia, thrombocytopenia, URTI, leukopenia, anaemia, rash | Rash, neutropenia, leukopenia, stomatitis, thrombocytopenia, nausea | Neutropenia, thrombocytopenia, URTI, leukopenia, anaemia, rash | Fatigue, bruising, diarrhoea, neutropenia, rash, nausea | URTI, back pain, bruising, cough, nausea, diarrhoea |
bid twice-daily, BTK Bruton tyrosine kinase, CLL chronic lymphocytic leukaemia, ESRD end-stage renal disease, MCL mantle cell lymphoma, MZL marginal zone lymphoma, PCNSL primary central nervous system lymphoma, QD once daily, URTI upper respiratory tract infection, WM Waldenström’s macroglobulinaemia
aIn B-cell malignancies
bDose reduction, interruption or discontinuation may be required to manage toxicities; dose reduction may be required for hepatic impairment