Table 2 Clinical trials of ibrutinib combination strategies in B-cell lymphoma

Ibrutinib-Anti-CD20 Monoclonal Antibody

Ibrutinib-Rituximab (IR)

Burger et al. (2019)

R/R CLL

II

40 pts with high-risk CLL

36-month PFS 86.9%

[39]

Burger et al. (2019)

CLL

NA

208 pts, 181 pts with R/R CLL, 27 TN pts with high-risk disease

36-month ORR 92%, PFS 86.9%

[34]

Jain et al. (2017)

R/R MCL

II

50 pts

ORR 88%, CR 58%, PR 30%

[42]

Dimopoulos et al. (2018)

WM

III

150 pts

MRR 72%, 30-month PFS 82%

[44]

Ibrutinib-Obinutuzumab

Moreno et al. (2019)

TN CLL

III

116 pts

ORR 88%, CR 19%, 30-month PFS 79%

[36]

Ibrutinib-Ofatumumab

Jaglowski et al. (2015)

CLL

Ib/II

66 pts, ibrutinib lead-in (group 1), concurrent start (group 2), or ofatumumab lead-in (group 3)

ORR were 100%, 79% and 71%; 12-month PFS 89%, 85%, 75% in group1 ~ 3, respectively

[37]

Ibrutinib-Ublituximab

Sharman et al. (2017)

R/R CLL

II

45 pts

6-month ORR 88%, pts with high-risk ORR 95%

[38]

Ibrutinib-Chemoimmunotherapy

Ibrutinib-BR

Fraser et al. (2019)

R/R CLL

III

289 pts

36-month PFS 68%, OS 81.6%

[45]

Brown et al. (2015)

R/R CLL

Ib

30 pts

ORR 93.3%, CR 40%, OS 74%, PFS 86.3%

[46]

Chanan-Khan et al. (2016)

R/R CLL

III

289 pts

ORR 83%, CR10%, PFS 79%

[48]

Ibrutinib-FCR

Davids et al. (2019)

CLL

II

85 pts, 5% del17p, 4% TP53 mutations, 2 pts with both

16.5-month CR 33%

[42]

Brown et al. (2015)

R/R CLL

Ib

3 pts

ORR 100%, CR 67%, PFS 70.3%

[46]

Shanafelt et al. (2019)

CLL

III

354 pts to IR group, 175 pts to the FCR group

33.6-month PFS 89.4% vs. 72.9%; OS 98.8% vs. 91.5%

[48]

Ibrutinib-R-ICE

Sauter et al. (2018)

DLBCL

I

21 pts

ORR 90%, CR 55%, PR 35%

[49]

DA-TEDDI-R

Lionakis et al. (2017)

PCNSL

Ib

18 pts

ORR 86%

[35]

Ibrutinib-R-CHOP

Younes et al. (2014)

NHL

Ib

32pts

ORR 94%

[50]

Ibrutinib-R-HD-MTX

Grommes et al. (2019)

R/R CNSL

Ib

15 pts

19.7-month ORR 80%, CR 53.3%, PR 26.7%

[51]

Ibrutinib-Biotarget Agents

Ibrutinib-Rituximab-Lenalidomide

Ujjani et al. (2018)

R/R CLL

I

12 pts

ORR 67%, 12-month PFS 83%

[62]

Jerkeman et al. (2018)

R/R MCL

II

50 pts

ORR 76%, CR 56%, PR 20%

[2]

Ujjani et al. (2016)

FL

I

22 pts

ORR 95%, 12-month PFS 80%

[63]

Ibrutinib-Venetoclax

Jain et al. (2019)

TN CLL

II

80 pts (untreated high-risk and the median age was 65 years)

CR or CR with incomplete count recovery 88%; 1-year PFS 98%, OS 99%

[60]

Tam et al. (2018)

R/R MCL

II

24 pts, 50% with TP53 mutation, 75% had high-risk prognostic score

CR 42%

[54]

Ibrutinib-Venetoclax-Obinutuzumab

Rogers et al. (2018)

R/R CLL

Ib

12 pts

ORR 92%, CR 42%

[55]

Ibrutinib-Palbociclib

Martain et al. (2019)

MCL

I

27 pts

25.6-month ORR 67%, CR 37%, PFS 59.4%

[54]

Ibrutinib-Umbralisib

Davids et al. (2019)

R/R CLL

Ib

21 elder pts with more than two previous therapies

ORR 90%, CR 29%, PR 62%

[57]

Davids et al. (2019)

R/R MCL

Ib

21 pts, median age of 68 years

ORR 67%, CR 19%, PR 48%

[57]

Ibrutinib-Umbralisib-Ublituximab

Nastoupil et al. 2019)

CLL

I

46 pts

ORR 84%

[58]

Ibrutinib-Nivolumab

Younes et al. (2019)

NHL

I/2a

141 pts

ORR, high-risk CLL/SLL 61%, FL 33%, DLBCL 36%

[59]