Table 4.

Select Agents in Development for the Treatment of DLBCL.^*

Class and Agent	Target	Clinical Trial Phase	Overall Response Rate	Complete Response Rate	Study
			percent
CAR T-cell therapy†
Axicabtagene ciloleucel	CD19	1	82	54	Neelapu et al.68
Tisagenlecleucel	CD19	2	52	40	Schuster et al.69
Lisocabtagene maraleucel	CD19	1	73	53	Abramson et al.67
Monoclonal antibodies
Tafasitamab	CD19	2a	26	6	Jurczak et al.70
Tafasitamab plus lenalidomide	CD19	2	60	43	Salles et al.71
Antibody-drug conjugates
Loncastuximab tesirine	CD19	1	42	23	Hamadani et al.72
Brentuximab vedotin	CD30	2	44	17	Jacobsen et al.73
Polatuzumab vedotin	CD79b	1	52‡	13‡	Palanca-Wessels et al.74
Polatuzumab vedotin plus BR vs. BR	CD79b	2, randomized	45 vs. 17.5	40 vs. 17.5	Sehn et al.75
Bispecific antibodies
Blinatumomab	CD19-CD3	2	43	19	Viardot et al76
Mosunetuzumab	CD20-CD3	1/1b	35§	19§	Schuster et al.77
Glofitamab	CD20-CD3	1/1b	41	29	Hutchings et al.78
Odronextamab	CD20-CD3	1	42¶	35¶	Bannerji et al.79
Epcoritamab	CD20-CD3	1/2	76‖	32‖	Hutchings et al.80
NF-κB and BCR modifiers
Ibrutinib	BTK	1/2	37 ABC, 5 GCB	16 ABC, 0 GCB	Wilson et al.81
Lenalidomide vs. investigator’s choice	Multiple, NF-κB	2, randomized	28 vs. 12	10 vs. 2	Czuczman et al.82
Agents with other targets
Venetoclax	BCL2	1	18	12	Davids et al.83
Selinexor	XPO1	2b	28	12	Kalakonda et al.84
Checkpoint inhibitors
Nivolumab	PD-1	2	≤10	≤3	Ansell et al.85
Magrolimab	CD47	1b	40	33	Advani et al.86
Epigenetic modifiers
Tazemetostat	EZH2	2	17 EZH2 mt, 17 EZH2 wt	3 EZH2 mt, 9 EZH2 wt	Ribrag et al.87

^*Results from early clinical trials involving patients with relapsed or refractory DLBCL are shown. BCL2 denotes B-cell lymphoma 2, BCR B-cell receptor, BR bendamustine plus rituximab, BTK Bruton’s tyrosine kinase, EZH2 enhancer of zeste homologue 2, mt mutant, NF-κB nuclear factor κB, PD-1 programmed cell death protein 1, wt wild type, and XPO1 exportin 1.

^†The three CD19-specific chimeric antigen receptor (CAR) T-cell products differ in the nature of the CAR construct and in the manufacturing processes (axicabtagene ciloleucel comprises bulk T cells retrovirally transduced with a receptor containing the CD28 costimulatory domain; tisagenlecleucel comprises bulk T cells lentivirally transduced with a receptor containing the 4−1BB costimulatory molecule; and lisocabtagene maraleucel comprises a 1:1 mix of CD4+ and CD8+ T cells separately transduced with a lentiviral vector coding for a receptor with the 4−1BB costimulatory domain). The bispecific CD3–CD20 antibodies present several differences in the antigen recognition domains of the antibodies and the number of binding sites to CD20, as well as in the route of administration (intravenous vs. subcutaneous). For these bispecific antibodies, early data from dose-escalation studies are presented.

^‡Results pertain to patients receiving a dose of 1.8 mg per square meter of body-surface area or higher.

^§Results pertain to the aggressive non-Hodgkin’s lymphoma cohort.

^¶Results pertain to patients receiving a dose of 80 mg or higher.

^‖Results pertain to patients receiving a dose of 12 mg or higher.