Table 2 Clinical trials involving BTK inhibitors combined with BCL2 inhibitors and anti-CD20 monoclonal antibodies in treating CLL and MCL

Ibrutinib+venetoclax+obinutuzumab

NCT02427451

2

TN and R/R CLL

50

uMRD in both PB and BM: 56% (TN) and 44% (R/R)

3-year PFS: 95% in both cohorts

3-year OS: 95% (TN) and 100% (R/R)

[51]

CLL2-GIVe

NCT02758665

2

TN CLL (high-risk)

41

15-month CR: 58.5%

15-month uMRD in PB/BM: 78% /65.9%

2-year PFS/OS: 95.1%/95.1%

[52]

OAsIs

NCT02558816

1/2

TN and R/R MCL

48

6-month CR: 67% (R/R) and 86.6% (TN)

2-year PFS and OS rates (R/R): 69.5 and 68.6%

1-year PFS (TN): 93.3%

[53]

Acalabrutinib+venetoclax+obinutuzumab

NCT03580928

2

TN CLL

44

16-month CR/CRi: 43%

16-month uMRD in PB/BM: 84%/78%

[54]

Acalabrutinib+venetoclax+obinutuzumab or rituximab

CL-003

NCT02296918

1b

TN and R/R CLL/SLL

24

16-month CR/CRi: 50% in both cohorts

10-month uMRD in PB: 67% (R/R) and 75% (TN)

18-month PFS/OS: 100%/100% in both cohorts

[55]

Acalabrutinib+venetoclax+rituximab

NCT02717624

1b

TN MCL

21

6-month CR/PR: 90%/10%

1-year PFS/OS: 89%/95%

6-month uMRD in PB: 75%

[56]

Zanubrutinib+venetoclax+obinutuzumab

NCT03824483

2

TN CLL/SLL

39

26-month uMRD in PB/BM: 95%/89%

[57]

NCT03824483

2

TN MCL (TP53mut)

25

Ongoing

[58]