Table 6 Available options after CAR-T cell therapy failures in R/R DLBCLs

Pola-BR (GO29365)

NCT02257567

Anti-CD79b/anti-CD20 immunochemotherapy

ORR/CRR, 70% (28/40)/57.5% (23/40)

mDOR, 10.3mo

mPFS, 7.6 mo

mOS, 12.4 mo [29]

ORR/CRR, 72%/33% [283]

Anemia (53.8%), neutropenia (53.8%), thrombocytopenia (48.7%), diarrhea (38.5%), nausea (30.8%), fatigue (35.9%), pyrexia (33.3%), peripheral neuropathy (43.6%)

Loncastuximab-tesirine

Anti-CD19 immunotherapy

ORR/CRR, 48.3% (70/145)/24.1% (35/145)

mDOR, 10.3 mo

mPFS, 4.9 mo

mOS, 9.9 mo [19]

ORR/CRR, 46.2% (6/13)/15.4% (2/13) Median DOR, 8 mo

Median PFS, 1.4 mo

Median OS, 8.2 mo [284]

Mild (no adverse events occurred more than 30%)

Tafasitamab-lenalidomide

Anti-CD19 immunotherapy/ immunomodulation

ORR/CRR 57.5% (46/80)/ 40% (32/80)

mDOR, 43.9 mo

mPFS, 11.6 mo

mOS, 33.5 mo [12]

ORR/CRR, 33%/17% [283]

Neutropenia (49%), anemia (34%), thrombocytopenia (31%), rash (36%), diarrhea (33%)

Mosenetuzumab

(NCT02500407)

T-cell-engaging bispecific antibody

ORR/CRR, 33% (13/39)/ 21% (8/39) [49]

ORR/CRR, 36.8% (7/19)/26.3% (5/19) [50]

Neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), diarrhea (21.8%)

Glofitamab

(NCT03075696)

T-cell-engaging bispecific antibody

ORR/CRR, 51.6 (80/155)/39.4% (61/155) [57]

not available

Pyrexia (46.2%), hypotension (24.6%), tachycardia (15.8%), chills (12.3%)

Odronextamab ≥ 80 mg (NCT02290951)

T-cell-engaging bispecific antibody

ORR/CRR, 60% (6/10)/60% (6/10) [39]

ORR/CRR, 33.3% (7/21)/23.8% (5/21)

mDOR, 2.4 mo [39]

pyrexia (76.4%), CRS (62.2%), and chills (48.0%)

Epcoritamab

(NCT03625037)

T-cell-engaging bispecific antibody

ORR/CRR, 63.1% (99/157)/38.9% (61/157)

mDOR, 12.0 mo

mPFS, 4.4 mo

mOS, not reached [54]

ORR/CRR, 54% (33/61)/34% (21/61) [54]

CRS (49.7%), injection site reaction (19.7%), and neutropenia (17.8%)

Selinexor

(NCT02227251)

XPO1 inhibitor

ORR/CRR, 28.3% (36/127)/11.8% (15/127)

mPFS 2.6 months

mOS 9.1 months [213]

Not available

Thrombocytopenia (61%), nausea (58%), fatigue (47%), anaemia (43%), decreased appetite (37%), diarrhoea (35%), constipation (31%), neutropenia (30%), weight loss (30%)

Allo-SCT

Allogeneic hematopoietic stem cell transplantation

ORR/CRR, 73.9% (17/23)/69.6% (16/23) [266]

Not available

cGVHD at 1 year (48%)

Pembrolizumab (49%)

Nivolumab (43%)

Atezolizumab (6%)

Others (2%)

PD-1/PD-L1

ORR/CRR, 11.8%/7.8%

mDOR, 7.5 mo

mPFS, 1.8 mo

mOS, 4.7 mo [79]

ORR, 33–35% [283]

Cytopenias, infections, pneumonitis, colitis, and hepatotoxicity (no adverse events occurred more than 30%)

Ibrutinib based

BTK inhibitor

ORR (ABC group), 37% (14/38)

ORR (GCB group), 5% (1/20) [157]

ORR/CRR, 38%/25% [283]

Fatigue (40%), diarrhea (38%), nausea (30%)

Lenalidomide based

Immunomodulation ± immunochemotherapy

ORR/CRR (R2), 28% (9/32)/22% (7/32) [255]

ORR/CRR, 58%/29% [283]

Anemia (88%), neutropenia (100%), thrombocytopenia (94%), leukopenia (91%), lymphopenia (100%), non-neutropenic fever (42%), fatigue (83%), constipation (38%), nausea (43%), neuropathy (58%), blurred vision (31%), myalgia (49%), diarrhea (51%), elevated liver function test (35%), hypocalcemia (30%), raised lactic dehydrogenase (53%), hyperglycemia (47%), hypoalbuminemia (40%), hypophosphatemia (36%)

R-ICE/R-DHAP

Immunochemotherapy

ORR/CRR, 63%/38% [174]

ORR/CRR, 35%/12% [283]

Grade 3/4 hematologic toxicities were more severe in the R-DHAP, more patients required at least one platelet transfusion during the induction phase (57% in R-DHAP arm v 35% in R-ICE arm)

Local radiotherapy

Salvage radiotherapy

ORR/CRR, 78.5% (11/14) /57.1% (8/14) [276]

ORR/CRR, 25%/13% [283]

Not available