Table 4.

Evidence of BTK inhibitors in patients with MCL

Patients type	Treatment regimen	Efficacy	Study	Phase	Patients (N)
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	50
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	17
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	807
	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	47
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	523
	Zanubrutinib + rituximab vs. BR	Ongoing	MANGROVE [65]	3	500
Patients with R/R MCL
Overall	Zanubrutinib	ORR: 83.7%; CR rate: 77.9%; median PFS: 33 months	BGB-3111–206 [72]	2	86
	Acalabrutinib	ORR: 81%; CR rate: 40%; 12-month PFS rate: 67%, 12-month; OS rate: 87%	ACE-LY-004 [14]	2	124
	Ibrutinib	ORR: 68%; CR rate: 21%; median PFS: 13.9 months	PCYC-1104 [8]	2	111
	Orelabrutinib	ORR: 82.5%; CR rate: 24.7%	ICP-022-MCL [73]	2	97

ASCT, autologous stem cell transplantation; BR, bendamustine plus rituximab; BTK, Bruton tyrosine kinase; CR, complete response; FFS, failure-free survival; MCL, mantle cell lymphoma; MRD, minimal residual disease; PFS, progression-free survival; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; R/R, relapsed/refractory; SLL, small lymphocytic lymphoma; ORR, overall response rate; OS, overall survival