Table 1.
Efficacy and safety of selected novel therapies in B-cell lymphomas.
| Target | Treatment | Phase | Nb of pts | Pathology | ORR (%) | CR (%) | Median PFS (mo) | DOR (mo) | Median f-u (mo) | Adverse Effects | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Small Molecule Inhibitors | |||||||||||
| BTK | Ibrutinib | case report | 1 | PCDLBCL, LT | 100 | 100 | ND | 18 | ND | ND | Gupta et al. |
| BTK | Acalabrutinib | II | 124 | R/R MCL | 81 | 40 | NR | NR | 15,2 | headache, gd 3 hematologic events, pneumonia | Wang et al. |
| BTK | Zanubrutinib | I | 78 | R/R CLL/SLL | 96.2 | 2.6 | NR | ND | 13.7 | neutropenia, subcutaneous hemorrhage | Tam et al. |
| PI3Kδ | Parsaclisib | I/II | 72 | R/R NHL | 20 to 100 | 0 to 44 | ND | 4.4 to 13.5 | ND | diarrhea, nausea, neutropenia | Forero Torres et al. |
| PKCβ | Enzastaurin | III | 758 | DLBCL | 80 | ND | ND | ND | 48 | urine color change, prolonged QTc interval | Crump et al. |
| TLRs 7,8,9 | IMO-8400 | I/II | 6 | R/R DLBCL | Gastrointestinal disorders, hematologic events | NCT02252146 | |||||
| HDAC | Mocetinostat | II | 72 | R/R DLBCL, FL | 18.9/11.5 | 2.7/3.8 | 2.1/3.7 | ND | ND | fatigue, nausea, diarrhea | Batlevi et al. |
| Bcl-2 | Venetoclax | I | 106 | R/R NHL | 44 | 13 | 6 | ND | ND | gd 3 hematologic events | Davids et al. |
| Monoclonal Antibodies | |||||||||||
| CD20 | Ofatumumab | III | 36 | FL | 84 | 16 | 1.9 | 23.7 | 30.7 | gd 3 infusion reactions | Rosenbaum et al. |
| CD20 | Ofatumumab | II | 11 | R/R DLBCL | 18 | 0 | 2 | ND | 38 | diarrhea, anorexia, hyponatremia, fatigue | Galanina et al. |
| CD19 (+proteasome) | MOR-208 (+ lenalidomide) | II | 81 | R/R DLBCL | 54 | 32 | 16,2 | NR | 12 | gd 3 neutropenia | Salles et al. |
| CD40 | Dacetuzumab | II | 46 | R/R DLBCL | 9 | 4 | 1.2 | ND | ND | thrombosis, ocular events, gd 3/4 hematologic events | Sven de Vos et al. |
| CD79 b (+ CD20) | Polatuzumab vedotin (+ rituximab) | II | 59 | R/R DLBCL, FL | 54/70 | 21/45 | 5.6/15.3 | 13.4/9.4 | 17.4/NE | hematologic events, diarrhea | Morschhauser et al. |
| BiTE Antibodies | |||||||||||
| CD19/CD3 | Blinatumomab | II | 21 | R/R DLBCL | 43 | 19 | 3.7 | 13.4 | ND | tremor, gd 3 neurologic events | Viardot et al. |
| CD20/CD3 | Mosunetuzumab | I/Ib | 218 | R/R NHL | 43.8 | 25 | ND | ND | ND | CRS 28.4%, neurological events 44% | Schuster et al. |
| Fusion Proteins | |||||||||||
| CD20 | DI-Leu16-IL2 | I | 9 | NHL | NCT00720135 | ||||||
| Tumor Vaccine | |||||||||||
| Idiotype protein | Mitumprotimut T | III | 174 | FL | 64 | 40 | ND | ND | ND | injection site reactions | Freedman et al. |
| Idiotype gene | DNA vaccine | I | ND | NHL | ISRCTN31090206 | ||||||
| APCs | Cellular vaccine | pilot | 18 | NHL | 33.3 | 16% | ND | ND | 50.5 | injection site reactions | Di Nicola et al. |
| Dendritic cells | In situ vaccine | I/II | 30 | Indolent BCL | NCT01976585 | ||||||
| Immune Check Point Inhibitors | |||||||||||
| CTLA-4 (+ CD20) | Ipilimumab (+ rituximab) | I | 33 | R/R NHL | 24 | 6 | 2.6 | ND | ND | diarrhea, rash, abdominal pain | Tuscano et al. |
| CAR T-Cell | |||||||||||
| CD19 CAR-T cells | Axicel | II | 111 | R/R LBCL | 82 | 54 | 5.8 | 8.1 | 15.4 | CRS 13%, neurological events 28% | Neelapu et al. |
| CD19 CAR-T cells | Tisagenlecleucel | II | 93 | R/R DLBCL | 52 | 40 | NR | ND | ND | CRS 22%, neurological events 12% | Schuster et al. |
| CD19 CAR-T cells (+ PD-1) | CD19 CAR-T cells (+ Nivolumab) | 11 | R/R DLBCL | 81.8 | 45.4 | 6 | 6 | 6 | CRS 50%, neurological events 1% | Cao et al. | |
| CD19 CAR-T cells + PD-1 | Pembrolizumab | I/II | 12 | R/R NHL after CD19 CAR-T cell | NCT02650999 | ||||||
| CD19 CAR-T cells | CD19 CAR-T cells + IL-2 | I | 60 | BCL | NCT00968760 |
APCs, antigen-presenting cells; BCL, B-cell lymphoma; BTK, Bruton tyrosine kinase; CLL/SLL, chronic lymphocytic leukemia/Small lymphocytic leukemia; CR, complete response; CRS, cytokine release syndrome; DLBCL diffuse large B-cell lymphoma; DOR, duration of response; f-u, follow-up; FL, follicular lymphoma; Gd, grade; HDAC, histone deacetylases; MCL, mantle cell lymphoma; mo, months; Nb, number; ND, not documented; NE, not estimable; NHL, non-Hodgkin lymphoma; NR, not reached; ORR, overall response rate; PCDLBCL, LT, primary cutaneous diffuse large B-cell lymphoma, leg type; PFS, progression free survival; PI3 Kδ, phosphatidylinositol 3-kinaseδ; PKCβ, protein kinase C β; Pts, patients; R/R, refractory/relapse.