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

From: Ibrutinib in B-cell lymphoma: single fighter might be enough?

  Therapeutic regimens Study (year) Disease Phase Study details Efficacy Refs.
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]
  1. Pts, Patients; CLL/SLL, Chronic lymphocytic leukemia/small lymphocytic lymphoma; WM, Waldenstroms macroglobulinemia; MCL, Mantle cell lymphoma; MZL, PFS, Progression-free survival; PR, partial response; CR, Complete response; ORR, Overall response rate; MRR, Major response rate; OS, Overall survival; R/R, Relapsed/refractory; TN, Treatment-native; FCR, Fludarabine combined with cyclophosphamide and rituximab; R-ICE, Rituximab, ifosfamide, carboplatin, etoposide; R-CHOP, Rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone; R-HD-MTX, High-dose methotrexate; High-risk, Pts with del17p, del11q or with TP53 mutations