Table 4 Evidence of BTK inhibitors in patients with MCL

Patients with treatment naïve MCL

Indolent clinical forms

Ibrutinib + rituximab

ORR: 84%; CR rate: 80%; estimated PFS at 36 months: 93%

IMCL-2015 [62]

2

Untreated MCL

Zanubrutinib + rituximab followed by rituximab (375 mg/m²), dexamethasone (20 mg), cytarabine (2000 mg/m²), and oxaliplatin (130 mg/m²) (R-DHAOx) then zanubrutinib maintenance

CR rate: 88.2% (15/17); MRD negative rate: 100%

Study ongoing

NCT04624958 [173]

2

ASCT eligible

Ibrutinib + R-CHOP followed by w/wo ASCT + ibrutinib maintenance

ORR: 98%; CR rate: 45%; 3-year FFS rate: 86%

TRIANGLE [66]

3

Zanubrutinib + rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m², prednisone 100 mg, (R-CHOP)/ dexamethasone 40 mg, rituximab 375 mg/m², cytarabine 2 × 2 g/m², cisplatin 100 mg/m² (R-DHAOx) ± ASCT

CR: 85.7% (6/7); MRD negative rate: 100%

Study ongoing

NCT04736914 [64]

2

ASCT ineligible

Ibrutinib + BR vs. placebo + BR

Median PFS: 80.6 vs. 52.9 months; CR rate: 65.5% vs. 65.5%

SHINE [63]

3

Zanubrutinib + rituximab vs. BR

Ongoing

MANGROVE [65]

3

Patients with R/R MCL

Overall

Zanubrutinib

ORR: 83.7%; CR rate: 77.9%; median PFS: 33 months

BGB-3111–206 [72]

2

Acalabrutinib

ORR: 81%; CR rate: 40%; 12-month PFS rate: 67%, 12-month; OS rate: 87%

ACE-LY-004 [14]

2

Ibrutinib

ORR: 68%; CR rate: 21%; median PFS: 13.9 months

PCYC-1104 [8]

2

Orelabrutinib

ORR: 82.5%; CR rate: 24.7%

ICP-022-MCL [73]

2