Table 2.

Emergent prognostic biomarkers for CD3×CD20 BsAbs

BiomarkerStudy designDiseaseNumber of patientsRelevant bispecificPrior therapiesImpact
Patient factors       
IPI ≥3 Prospective3,8  LBCL 157 Epcoritamab ≥1 prior line Lower CR rate 
   88 Mosunetuzumab ≥2 prior lines  
FLIPI ≥3 Prospective7  FL 128 Epcoritamab ≥1 prior line Lower CR rate 
ECOG >0 Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior OS 
Female sex Prospective4,8  LBCL 157 Epcoritamab ≥1 prior line Higher CR rate 
   154 Glofitamab ≥1 prior line  
Age ≥65 y Prospective1,3,7,8  LBCL 157 Epcoritamab ≥1 prior line Higher CR rate 
  FL 88 Mosunetuzumab ≥2 prior lines  
   128 Epcoritamab ≥1 prior line  
   90 Mosunetuzumab ≥2 prior lines  
Stage III or IV Prospective8,15  LBCL 40 Mosunetuzumab + CHOP Untreated Lower CR rate 
   157 Epcoritamab ≥1 prior line  
Elevated LDH Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior PFS 
 Prospective4,15  BCL 64 CD3×CD20 Prior CAR-T Inferior PFS/OS 
  LBCL 154 Glofitamab ≥1 prior line Lower CR rate 
   40 Mosunetuzumab + CHOP ≥2 prior lines  
Disease bulk Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior PFS 
 Prospective15,16  BCL 64 CD3×CD20 Prior CAR-T Lower CR rate 
  LBCL 40 Mosunetuzumab + CHOP untreated  
   98 Mosunetuzumab + PV ≥2 prior lines  
TMTV ≥128.7 mL Retrospective17  LBCL 144 Glofitamab ≥1 prior line Inferior PFS 
Prior anti-CD20 Prospective1,3,8,16  LBCL 157 Epcoritamab ≥1 prior line Lower CR rate 
  FL 88 Mosunetuzumab ≥2 prior lines  
   98 Mosunetuzumab + PV ≥2 prior lines  
   90 Mosunetuzumab ≥2 prior lines  
Anti-CD20 within 3 months Prospective16  LBCL 98 Mosunetuzumab + PV ≥2 prior lines Lower CR rate 
Refractory status Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior PFS 
Prior CAR-T Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior OS 
 Prospective1,3,11  LBCL 88 Mosunetuzumab ≥2 prior lines Lower CR rate 
  FL 45 Odronextamab ≥2 prior lines  
   90 Mosunetuzumab ≥2 prior lines  
Tumor biology       
CD20 expression, <10% Retrospective18  FL and LBCL 250 Mosunetuzumab ≥2 prior lines Lower ORR rate 
Non-GCB cell of origin Prospective4,8,16  LBCL 157 Epcoritamab ≥1 prior line Lower CR rate 
   154 Glofitamab ≥1 prior line  
   98 Mosunetuzumab + PV ≥2 prior lines  
Double expressor Prospective4,15  LBCL 154 Glofitamab ≥1 prior line Lower CR rate 
   40 Mosunetuzumab + CHOP ≥2 prior lines  
Double hit Retrospective19  BCL 64 CD3×CD20 Prior CAR-T Inferior PFS/OS 
 Prospective4,15,16  LBCL 154 Glofitamab ≥1 prior line Lower CR rate 
   40 Mosunetuzumab + CHOP ≥2 prior lines  
   98 Mosunetuzumab + PV ≥2 prior lines  
HGBL Prospective4,16  LBCL 154 Glofitamab ≥1 prior line Lower CR rate 
   98 Mosunetuzumab + PV ≥2 prior lines  
Increased MYC signatures Retrospective20  LBCL 35 Glofitamab ≥1 prior line Lower CR rate 
Molecular aberrations: TP53, RHOA, GNAI2, CD274 Retrospective20,21  LBCL 33 Glofitamab ≥1 prior line Lower CR rate 
   34 CD3×CD20  Inferior OS 
Molecular aberrations: EZH Prospective1  FL 90 Mosunetuzumab ≥2 prior lines Lower CR rate 
MRD negativity Prospective13,22  LBCL 107 Epcoritamab ≥1 prior line Improved PFS 
  FL 64 Odronextamab ≥2 prior lines  
Increased tumoral exhausted CD8+ T cells Retrospective23  LBCL 7 CD3×CD20 ≥1 prior line Higher relapse rate 
Higher PD-1 expression Retrospective20  LBCL 35 Glofitamab ≥1 prior line Associated with PD 
Higher PD-L1 expression Retrospective24  LBCL and FL 89 Odronextamab ≥2 prior lines Higher ORR rate 
Tumor extrinsic immune competency       
Higher BL PB CD19+ Retrospective25  LBCL 87 Glofitamab ≥1 prior line Higher CR rate 
B cells Prospective3   90 Mosunetuzumab ≥2 prior lines  
Lower BL levels of CRP, IL-6, and IL-8 Retrospective 20,25   119 Glofitamab ≥1 prior line Higher CR rate 
   87    
Greater reduction of PB CD3+ T cells with treatment Retrospective20  LBCL 119 Glofitamab ≥1 prior line Higher CR rate 
BiomarkerStudy designDiseaseNumber of patientsRelevant bispecificPrior therapiesImpact
Patient factors       
IPI ≥3 Prospective3,8  LBCL 157 Epcoritamab ≥1 prior line Lower CR rate 
   88 Mosunetuzumab ≥2 prior lines  
FLIPI ≥3 Prospective7  FL 128 Epcoritamab ≥1 prior line Lower CR rate 
ECOG >0 Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior OS 
Female sex Prospective4,8  LBCL 157 Epcoritamab ≥1 prior line Higher CR rate 
   154 Glofitamab ≥1 prior line  
Age ≥65 y Prospective1,3,7,8  LBCL 157 Epcoritamab ≥1 prior line Higher CR rate 
  FL 88 Mosunetuzumab ≥2 prior lines  
   128 Epcoritamab ≥1 prior line  
   90 Mosunetuzumab ≥2 prior lines  
Stage III or IV Prospective8,15  LBCL 40 Mosunetuzumab + CHOP Untreated Lower CR rate 
   157 Epcoritamab ≥1 prior line  
Elevated LDH Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior PFS 
 Prospective4,15  BCL 64 CD3×CD20 Prior CAR-T Inferior PFS/OS 
  LBCL 154 Glofitamab ≥1 prior line Lower CR rate 
   40 Mosunetuzumab + CHOP ≥2 prior lines  
Disease bulk Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior PFS 
 Prospective15,16  BCL 64 CD3×CD20 Prior CAR-T Lower CR rate 
  LBCL 40 Mosunetuzumab + CHOP untreated  
   98 Mosunetuzumab + PV ≥2 prior lines  
TMTV ≥128.7 mL Retrospective17  LBCL 144 Glofitamab ≥1 prior line Inferior PFS 
Prior anti-CD20 Prospective1,3,8,16  LBCL 157 Epcoritamab ≥1 prior line Lower CR rate 
  FL 88 Mosunetuzumab ≥2 prior lines  
   98 Mosunetuzumab + PV ≥2 prior lines  
   90 Mosunetuzumab ≥2 prior lines  
Anti-CD20 within 3 months Prospective16  LBCL 98 Mosunetuzumab + PV ≥2 prior lines Lower CR rate 
Refractory status Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior PFS 
Prior CAR-T Retrospective14  FL and LBCL 104 CD3×CD20 ≥1 prior line Inferior OS 
 Prospective1,3,11  LBCL 88 Mosunetuzumab ≥2 prior lines Lower CR rate 
  FL 45 Odronextamab ≥2 prior lines  
   90 Mosunetuzumab ≥2 prior lines  
Tumor biology       
CD20 expression, <10% Retrospective18  FL and LBCL 250 Mosunetuzumab ≥2 prior lines Lower ORR rate 
Non-GCB cell of origin Prospective4,8,16  LBCL 157 Epcoritamab ≥1 prior line Lower CR rate 
   154 Glofitamab ≥1 prior line  
   98 Mosunetuzumab + PV ≥2 prior lines  
Double expressor Prospective4,15  LBCL 154 Glofitamab ≥1 prior line Lower CR rate 
   40 Mosunetuzumab + CHOP ≥2 prior lines  
Double hit Retrospective19  BCL 64 CD3×CD20 Prior CAR-T Inferior PFS/OS 
 Prospective4,15,16  LBCL 154 Glofitamab ≥1 prior line Lower CR rate 
   40 Mosunetuzumab + CHOP ≥2 prior lines  
   98 Mosunetuzumab + PV ≥2 prior lines  
HGBL Prospective4,16  LBCL 154 Glofitamab ≥1 prior line Lower CR rate 
   98 Mosunetuzumab + PV ≥2 prior lines  
Increased MYC signatures Retrospective20  LBCL 35 Glofitamab ≥1 prior line Lower CR rate 
Molecular aberrations: TP53, RHOA, GNAI2, CD274 Retrospective20,21  LBCL 33 Glofitamab ≥1 prior line Lower CR rate 
   34 CD3×CD20  Inferior OS 
Molecular aberrations: EZH Prospective1  FL 90 Mosunetuzumab ≥2 prior lines Lower CR rate 
MRD negativity Prospective13,22  LBCL 107 Epcoritamab ≥1 prior line Improved PFS 
  FL 64 Odronextamab ≥2 prior lines  
Increased tumoral exhausted CD8+ T cells Retrospective23  LBCL 7 CD3×CD20 ≥1 prior line Higher relapse rate 
Higher PD-1 expression Retrospective20  LBCL 35 Glofitamab ≥1 prior line Associated with PD 
Higher PD-L1 expression Retrospective24  LBCL and FL 89 Odronextamab ≥2 prior lines Higher ORR rate 
Tumor extrinsic immune competency       
Higher BL PB CD19+ Retrospective25  LBCL 87 Glofitamab ≥1 prior line Higher CR rate 
B cells Prospective3   90 Mosunetuzumab ≥2 prior lines  
Lower BL levels of CRP, IL-6, and IL-8 Retrospective 20,25   119 Glofitamab ≥1 prior line Higher CR rate 
   87    
Greater reduction of PB CD3+ T cells with treatment Retrospective20  LBCL 119 Glofitamab ≥1 prior line Higher CR rate 

Improved CR rates must have been >10% difference.

BL, B-cell lymphoma; CRP, C-reactive protein; ECOG, Eastern Cooperative Oncology Group performance score; GCB, germinal center B cell; HGBL, high-grade BL; MRD, measurable residual disease; ORR, objective response rate; PV, polatuzumab vedotin.

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