Table 4.
Summary of clinical trials representing immunotherapeutic agents with ibrutinib combinations.
| Study | Patient | Size (M-Age) | Regimen | Outcome | Adverse Events | CT Identifier |
|---|---|---|---|---|---|---|
| Phase-3; Moreno [188] | CLL | 229 (65) | Obinutuzumab-IB vs. obinutuzumab- chlorambucil | 30-month PFS 79% vs. 31% | Serious adverse events: 58% vs. 35% | NCT02264574 (iLLUMINATE) |
| Phase-2; Burger [185] | CLL | 208 (65) | Rituximab-IB vs. IB | 36-month PFS 86.9% vs. 86% | Grade 3/4 TEAE: 65% vs. 64% | NCT02007044 |
| Phase-3; Woyach [184] | CLL | 547 (≥65) | BM-Rituximab vs IB-Rituximab vs. IB | 38-month OS –not significant | Grade 3-5 hematological adverse events: 61% vs. 39% vs. 41% | NCT01886872 |
| Phase-3; Meletios [182] | WM | 150 (69) | Rituximab-IB vs. Rituximab | 30-month PFS 82% vs. 28% | AF: (12% vs. 1%) Hypertension: (13% vs. 4%) | NCT02165397 |
| Phase-3; Meletios [189] | WM (Rituximab refractory) | 31 (67) | IB | 18-month PFS 86% OS 97% | Grade-3 events: Neutropenia-13%, Hypertension-10%. | NCT02165397 (iNNOVATE) |
| Phase-3; Khan [190] | CLL | 578 (≥18) | BM-rituximab vs. BM-Rituximab-IB | 18-month PFS 24% vs. 79% | Grade 3-4 neutropenia: 51% vs. 54% | NCT01611090 (HELIOS) |
| Phase-2; Wang [191] | MCL (R/R) | 50 (67) | Rituximab-IB | 16.5-month PR 44% CR 44% | Grade 3 AF: 12% Grade 4 neutropenia: 1 patient | NCT01880567 |
| Gauthier [12] | CLL (R/R) with del (17p) | 19 | CD19 CAR-T-cell-IB | 4-week ORR 83% | Lower CRS after addition of IB | - |
| Gong [192] | CLL R/R to venetoclax, del(17p) | 1 | CD19 CAR-T-cell-IB | 1-month CR, negligible MRD | Grade 1 CRS | - |
| Phase-1/2; Gauthier [193] | CLL (IB-resistant) | 43 | JCAR014-Cy-Flu-IB vs. JCAR014-Cy-Flu | 4-week ORR 88% vs. 56% | No difference in grade ≥3 cytopenias, similar grade ≥1 CRS | NCT01865617 |
| Phase-1/2; multicenter study | CLL/SLL | 200 | JCAR017 or JCAR017-IB | on-going | - | NCT03331198 |
| Phase-1 | Multiple B-cell malignancies | 274 | JCAR017 | on-going | - | NCT02631044 |
Abbreviations: IB, ibrutinib; BM, bendamustine; PFS, progression-free survival; OS, overall survival; CR, complete response; PR, partial response; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; WM, Waldenström’s macroglobulinemia; CT, clinical trial; M-age, median-age; Cy-Flu, cyclophosphamide, and fludarabine; AF, atrial fibrillation; TEAE, treatment emergence adverse event; CRS, cytokine release syndrome.