Comparison of structure, administration, CRS, and neurotoxicity associated with CD3×CD20 BsAbs in NHL
| Drug . | Mosunetuzumab3 . | Epcoritamab4 . | Glofitamab5 . | Odronextamab6,7 . | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Structure | Fully humanized IgG1 CD3×CD20 BsAb with 1:1 CD3:CD20 ratio of Fab arms | IgG-like anti-CD3×CD20 BsAb. Proprietary format, with point mutations in the Fab portion of the Fc of the antibody and heterodimerization. | Humanized mouse-derived BsAb with 1:2 CD3:CD20 ratio of Fab arms | Fully humanized IgG4 anti-CD3×CD20 BsAb developed using an Fc domain with a mutation in the protein A of the Fc portion | ||||||||||||||||
| Route of administration | IV | SC | IV | IV | ||||||||||||||||
| Dosing schedule | C1: days 1, 8, 15; C2+: day 1, every 21 d, for up to 8 cycles in CR or up to 17 cycles for PR or SD | C1-3: days 1, 8 ,15, and 22; C4-9: days 1 and 15; C10+: day 1, every 28 d until progression | C1: obin, day 1; glofit, days 8 and 15; C2-12: day 1, every 21 d | C1: days 1, 2, 8, 9, 15, 16 of a 21-d cycle; C2-4: days 1, 8, 15 of a 21-d cycle; C5+: day 1, every 14 d; If CR for at least 9 mo: day 1, every 28 d | ||||||||||||||||
| CRS mitigation | ||||||||||||||||||||
| Step-up dosing | C1D1: 1 mg C1D8: 2 mg C1D15: 60 mg C2D1: 60 mg C3+D1: 30 mg | C1D1: 0.16 mg C1D8: 0.8 mg C1D15: 48 mg C1D22: 48 mg C2D1+: 48mg | C1D1: obin 1000 mg C1D8: 2.5 mg C1D15: 10 mg C2D1+: 30 mg | C1D1: 0.2 mg C1D2: 0.5 mg C1D8: 2 mg C1D9: 2 mg C1D15: 10 mg C1D16: 10 mg C2-C4: 80 mg (FL) or 160 mg (DLBCL) C5+: 160 mg (FL) or 320 mg (DLBCL) | ||||||||||||||||
| Premedications | (1) A/P 500-1000 mg, 30 min prior, for C1 and C2 (2) Diphenhydramine 50-100 mg, 30 min prior, for C1 and C2 (3) Dexamethasone 20 mg or methylprednisolone 80 mg, 1 h prior, for C1 and C2. Continue all premedications if CRS with prior dose. | (1) A/P 650-1000 mg, 30-120 min before C1 treatments (2) Diphenhydramine 50 mg, 30-120 min before C1 treatments (3) Dexamethasone 15 mg, 30-120 min before C1 treatments and for 3 consecutive days after. Continue dexamethasone thereafter if G2 or G3 CRS with prior dose. | (1) A/P 500-1000 mg, 30 min before all treatments (2) Diphenhydramine 50 mg, 30 min before all infusions (3) Dexamethasone 20 mg, 1 h before treatment on C1D8, C1D15, C2D1, and C3D1. Continue if CRS with prior dose. | (1) A/P 650 mg, 30-60 min prior, during step-up dosing, continue if IRR or CRS with prior dose (2) Diphenhydramine 25 mg, 30-60 min prior during step-up dosing, continue if IRR or CRS with prior dose (3) Dexamethasone 10 mg orally, 12-24 h before split dose, 20 mg IV on day of dosing, 10 mg orally on the day after step-up dosing. Following first full dose, dexamethasone 10 mg before dosing; continue if CRS with prior dose. | ||||||||||||||||
| Hospitalization | Optional | C1D15: 24-h admission | C1D8: 24-h admission | Performed during step-up dosing | ||||||||||||||||
| CRS occurrence | G1 | G2 | G3 | G4 | G5 | G1 | G2 | G3 | G4 | G5 | G1 | G2 | G3 | G4 | G5 | G1 | G2 | G3 | G4 | G5 |
| 26% | 17% | 1% | 1% | 0% | 34% | 15% | 3% | 0% | 0% | 47% | 12% | 3% | 1% | 0% | 35%-39% | 13% (DLBCL) | 0% | 0% | 0% | |
| Time course for CRS onset | Median time (h) to CRS onset | Time course for CRS onset | Median time (h) to CRS onset | Time course for CRS onset | Median time (h) to CRS onset | Time course for CRS onset | Median time (h) to CRS onset | |||||||||||||
| C1D1: 23.3% C1D8: 5.6% C1D15: 36.4% C2D1: 10.3% C3+D1: 2.4% | C1D1: 5 C1D8: 20 C1D15: 27 C2D1: 38 | C1D1: 5.8% C1D8: 11.8% C1D15: 42.8% C1D22: 4.9% C3+ 3% | All doses: 24 C1D15: 20 | C1D8: 42.8% C1D15: 25.2% C2: 26% C3+: 0.9% | C1D8: 13.5 (range: 6-52) | C1D1/2: 22%-24% C1D8/9: 27%-32% C1D15/16: 21%-35% C2D1: 14%-17% C2D8+: 9%-14% | All doses: 18-20 | |||||||||||||
| Median duration of CRS | 3 d (1-29 d) | 2 d (range: 1-27 d) | 30.5 h (range, 0.5-317 h) | 8-10 h (range, 0.1-190 h) | ||||||||||||||||
| Neurotoxicity | G 1-2 | G3 | G4 | G5 | G1 | G2 | G3 | G4 | G5 | G 1-2 | G 3-4 | G5 | G 1-2 | G 3-4 | G5 | |||||
| 3% | 0% | 0% | 0% | 4.5% | 1.3% | 0% | 0% | 0.6% | 5% | 3% | 0% | 4% (DLBCL) | 0% | 0% | ||||||
| Drug . | Mosunetuzumab3 . | Epcoritamab4 . | Glofitamab5 . | Odronextamab6,7 . | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Structure | Fully humanized IgG1 CD3×CD20 BsAb with 1:1 CD3:CD20 ratio of Fab arms | IgG-like anti-CD3×CD20 BsAb. Proprietary format, with point mutations in the Fab portion of the Fc of the antibody and heterodimerization. | Humanized mouse-derived BsAb with 1:2 CD3:CD20 ratio of Fab arms | Fully humanized IgG4 anti-CD3×CD20 BsAb developed using an Fc domain with a mutation in the protein A of the Fc portion | ||||||||||||||||
| Route of administration | IV | SC | IV | IV | ||||||||||||||||
| Dosing schedule | C1: days 1, 8, 15; C2+: day 1, every 21 d, for up to 8 cycles in CR or up to 17 cycles for PR or SD | C1-3: days 1, 8 ,15, and 22; C4-9: days 1 and 15; C10+: day 1, every 28 d until progression | C1: obin, day 1; glofit, days 8 and 15; C2-12: day 1, every 21 d | C1: days 1, 2, 8, 9, 15, 16 of a 21-d cycle; C2-4: days 1, 8, 15 of a 21-d cycle; C5+: day 1, every 14 d; If CR for at least 9 mo: day 1, every 28 d | ||||||||||||||||
| CRS mitigation | ||||||||||||||||||||
| Step-up dosing | C1D1: 1 mg C1D8: 2 mg C1D15: 60 mg C2D1: 60 mg C3+D1: 30 mg | C1D1: 0.16 mg C1D8: 0.8 mg C1D15: 48 mg C1D22: 48 mg C2D1+: 48mg | C1D1: obin 1000 mg C1D8: 2.5 mg C1D15: 10 mg C2D1+: 30 mg | C1D1: 0.2 mg C1D2: 0.5 mg C1D8: 2 mg C1D9: 2 mg C1D15: 10 mg C1D16: 10 mg C2-C4: 80 mg (FL) or 160 mg (DLBCL) C5+: 160 mg (FL) or 320 mg (DLBCL) | ||||||||||||||||
| Premedications | (1) A/P 500-1000 mg, 30 min prior, for C1 and C2 (2) Diphenhydramine 50-100 mg, 30 min prior, for C1 and C2 (3) Dexamethasone 20 mg or methylprednisolone 80 mg, 1 h prior, for C1 and C2. Continue all premedications if CRS with prior dose. | (1) A/P 650-1000 mg, 30-120 min before C1 treatments (2) Diphenhydramine 50 mg, 30-120 min before C1 treatments (3) Dexamethasone 15 mg, 30-120 min before C1 treatments and for 3 consecutive days after. Continue dexamethasone thereafter if G2 or G3 CRS with prior dose. | (1) A/P 500-1000 mg, 30 min before all treatments (2) Diphenhydramine 50 mg, 30 min before all infusions (3) Dexamethasone 20 mg, 1 h before treatment on C1D8, C1D15, C2D1, and C3D1. Continue if CRS with prior dose. | (1) A/P 650 mg, 30-60 min prior, during step-up dosing, continue if IRR or CRS with prior dose (2) Diphenhydramine 25 mg, 30-60 min prior during step-up dosing, continue if IRR or CRS with prior dose (3) Dexamethasone 10 mg orally, 12-24 h before split dose, 20 mg IV on day of dosing, 10 mg orally on the day after step-up dosing. Following first full dose, dexamethasone 10 mg before dosing; continue if CRS with prior dose. | ||||||||||||||||
| Hospitalization | Optional | C1D15: 24-h admission | C1D8: 24-h admission | Performed during step-up dosing | ||||||||||||||||
| CRS occurrence | G1 | G2 | G3 | G4 | G5 | G1 | G2 | G3 | G4 | G5 | G1 | G2 | G3 | G4 | G5 | G1 | G2 | G3 | G4 | G5 |
| 26% | 17% | 1% | 1% | 0% | 34% | 15% | 3% | 0% | 0% | 47% | 12% | 3% | 1% | 0% | 35%-39% | 13% (DLBCL) | 0% | 0% | 0% | |
| Time course for CRS onset | Median time (h) to CRS onset | Time course for CRS onset | Median time (h) to CRS onset | Time course for CRS onset | Median time (h) to CRS onset | Time course for CRS onset | Median time (h) to CRS onset | |||||||||||||
| C1D1: 23.3% C1D8: 5.6% C1D15: 36.4% C2D1: 10.3% C3+D1: 2.4% | C1D1: 5 C1D8: 20 C1D15: 27 C2D1: 38 | C1D1: 5.8% C1D8: 11.8% C1D15: 42.8% C1D22: 4.9% C3+ 3% | All doses: 24 C1D15: 20 | C1D8: 42.8% C1D15: 25.2% C2: 26% C3+: 0.9% | C1D8: 13.5 (range: 6-52) | C1D1/2: 22%-24% C1D8/9: 27%-32% C1D15/16: 21%-35% C2D1: 14%-17% C2D8+: 9%-14% | All doses: 18-20 | |||||||||||||
| Median duration of CRS | 3 d (1-29 d) | 2 d (range: 1-27 d) | 30.5 h (range, 0.5-317 h) | 8-10 h (range, 0.1-190 h) | ||||||||||||||||
| Neurotoxicity | G 1-2 | G3 | G4 | G5 | G1 | G2 | G3 | G4 | G5 | G 1-2 | G 3-4 | G5 | G 1-2 | G 3-4 | G5 | |||||
| 3% | 0% | 0% | 0% | 4.5% | 1.3% | 0% | 0% | 0.6% | 5% | 3% | 0% | 4% (DLBCL) | 0% | 0% | ||||||
A/P, acetaminophen (paracetamol); C, cycle; CR, complete response; CRS, cytokine release syndrome; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; G, grade; glofit, glofitamab; IgG, immunoglobulin G; IRR, infusion-related reaction; obin, obinutuzumab; PR, partial response; SC, subcutaneous; SD, stable disease.