Table 6.
Evidence of BTK inhibitors in patients with CNSL
| Patients type | BTK inhibitor regimens | Efficacy | Study | Phase | N |
|---|---|---|---|---|---|
| TN, R/R CNSL | TN: zanubrutinib + rituximab R/R: zanubrutinib + HD-MTX (methotrexate at 3.5–5.0 g/m2 d1 and cytarabine at 2.0 g every 12 h on d2 and d3, every 21 days per cycle) + rituximab |
TN: ORR CR 100% (5/5) R/R: ORR, CR 60% (3/5) |
Zhang et al. [26] | Retrospective | 10 |
| Orelabrutinib + immunotherapy + chemotherapy + radiotherapy |
TN: ORR 100% (4/4); CR 25% (1/4) R/R: ORR 60% (9/15); CR 26.6% (4/15) |
Wu et al. [104] | Retrospective | 19 | |
| R/R CNSL | Tirabrutinib | ORR: 64%; CR/CRu 34%; PFS: 2.9 months; OS: NR | ONO-4059 [105] | 2 | 44 |
| Ibrutinib | ORR: 59%; CR: 23%; PFS: 4.8 months; OS: 19.2 months | NCT02542514 [107] | 2 | 52 | |
| Zanubrutinib + HD-MTX + rituximab | Achieved CR after adding zanubrutinib for 3 cycles | Cheng et al. [110] | Case report | 1 | |
| R/R CNSL/SCNSL | Ibrutinib + HD-MTX + rituximab | ORR: 80%; CR: 53.3% | NCT02315326 [108] | 1b | 15 |
| R/R CNSL/PVRL | Ibrutinib + DA-TEDDi-R | ORR: 93%; CR: 86% | Lionakis et al. [25] | 1b | 16 |
| R/R CNSL | Orelabrutinib + lenalidomide + rituximab + HD-MTX + TMZ | ORR: 86.7% (13/15); CR: 73.7% (11/13) | Yang et al. [109] | Retrospective | 15 |
BTK, Bruton tyrosine kinase; CNSL, central nervous system lymphoma; SCNSL, secondary CNSL; CR, complete response; DA-TEDDi-R, rituximab, liposomal doxorubicin, temozolomide, etoposide and dexamethasone; HD-MTX, high-dose methotrexate; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PVRL, primary vitreoretinal lymphoma; R/R, relapsed/refractory; TN, treatment naïve