Table 7 Evidence of BTK inhibitors in patients with WM

Patients with WM (Overall)

TN

Ibrutinib + rituximab

PFS: NR (rate 68%); RR: 76%, PR: 45%; VGPR: 29%; CR: 1%; TTNT: NR

iNNOVATE [113]

3

75

R/R

Ibrutinib

RR: 77%; VGPR: 29%; PR: 48%

iNNOVATE [114]

3

31

R/R

Ibrutinib

ORR: 90.5%, MRR: 79.4%, 5-year OS: 87%

NCT01614821 [115]

2

63

TN

Zanubrutinib

MR: 87.5%; VGPR: 33.3%; PR: 54.2%

BGB-3111-AU003 [175]

1/2

24

R/R

Zanubrutinib

MR: 79.6%; VGPR: 49%; PR: 28.6%

BGB-3111-AU003 [175]

1/2

49

TN

Zanubrutinib

MR: 64%; VGPR: 27%; PR: 36%

NCT04052854 [176]

2

11

R/R

Zanubrutinib

MR 90%; VGPR: 43%; PR: 33%

NCT04052854 [176]

2

30

R/R

Zanubrutinib

MR: 69.8%; VGPR: 32.6%

BGB-3111–210 [177]

2

44

TN

Zanubrutinib

MR: 21%; PR: 47%; VGPR: 26%

ASPEN [112]

3

19

R/R

Zanubrutinib

MR: 16%; PR: 49%; VGPR: 29%

ASPEN [112]

3

83

TN

Acalabrutinib

ORR: 93%; MR: 14%; PR: 71%; VGPR: 7%

NCT02180724 [178]

2

14

R/R

Acalabrutinib

ORR: 94%; MR: 15%; PR 47%; VGPR: 32%

NCT02180724 [178]

2

92

R/R

Orelabrutinib

MR: 80.9%; VGPR: 21.3%; PR: 59.6%

ICP-CL-00105 [179]

2

47

WM patients with MYD88 mutation

MYD88^L265PCXCR4^WT

Ibrutinib

ORR: 100%; MRR: 91.2%

NCT01614821 [119]

2

34

R/R: 34; TN: 2

Acalabrutinib

ORR: 94%; MRR: 78%

NCT02180724 [178]

2

36

MYD88^L265PCXCR4^WT

Orelabrutinib

MRR: 84.6%

ICP-CL-00105 [179]

2

–

MYD88 mutation

Zanubrutinib vs. ibrutinib

CR + VGPR: 36.3% vs. 25.3%

ASPEN [180]

3

201

WM patients with MYD88 wild type

MYD88^WTCXCR4^WT

Ibrutinib

ORR: 71.4%; MRR: 28.6%

NCT01614821 [119]

2

7

R/R: 13; TN: 1

Acalabrutinib

ORR: 79%; MRR: 57%

NCT02180724 [178]

2

14

MYD88^WTCXCR4^WT

Orelabrutinib

ORR: 25%

ICP-CL-00105 [179]

2

–

MYD88WT

Zanubrutinib

MRR: 65% (including 34% CR + VGPR)

ASPEN [120]

3

28

WM patients with CXCR4 mutation

MYD88^MutCXCR4^Mut

Ibrutinib

MRR: 68.2%; VGPR: 9.1%; median PFS: 38%

NCT01614821 [115]

2

2

CXCR4 mutation

Zanubrutinib vs. ibrutinib

VGPR: 21% vs. 10%

MRR: 79% vs. 65%

ASPEN [120]

3

201