Topline Presentation Points

Relapsed and Refractory DLBCL: Current Status 

Antibody drug conjugates: 

Polatuzumab vedotin  

Mechanism of action 

(Pola) is an antibody drug conjugate (ADC) consisting of a potent microtubule inhibitor monomethyl auristatin E (MMAE) conjugated to CD79b monoclonal antibody via a protease-cleavable peptide linker 

Clinical Activity 

  • Pola has demonstrated efficacy in R/R DLBCL in combination with rituximab
    (Palanca-Wessels A, et al. Lancet Oncol, 2015;16:704-15)
    (Morschhauser F, et al. Lancet Hematology, 2019;6:e254 -65)
  • Polatuzumab vedotin added to bendamustine/ rituximab in R/R DLBCL 
  • The significant survival benefit with Pola+BR persists with longer follow-up  
  • Eleven patients (28%) from the randomized Pola+BR cohort are long-term survivors with OS >24 months (range: 28.0–52.5 months)

    (Sehn LH, et al. J Clin Oncol. 2020 Jan 10;38(2):155-165.)
    (Sehn et al, ASH 2020, Poster 30)

Loncastuximab tesirine 

Response by Histology – Lotis-2 study

(Caimi et al., Lancet Oncology 2021)


Mechanism of Actio 

Selective Inhibitor of Nuclear Export (SINE) compound that inhibits XPO1 to force nuclear retention of tumor suppressors and other proteins integral to tumorigenesis 

Clinical activity 

  • Selinexor single agent activity in R/R DLBCL

    (Kalakonda N et al. Lancet Haematol. 2020;7(7):e511-e522.)


Cellular Therapy 

Anti-CD19 CAR-T Cell Therapies in R/R aggressive NHL 

  • Long term follow up of CAR-T pivotal studies –  
  • ZUMA-1 (Axi-cel) 
    • The KM estimate of the 4-year OS rate was 44% 
    • Median OS was 25.8 months (Jacobson CA et al. 2021 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR. Abstract 494.)
    • Post clinical trials of PFS and OS (Nastoupil LJ et al, JCO 2020)
  • JULIET (Tisa-cel) 
    • 36-month PFS = 31% ; 36 months OS = 36% 

           Jaeger U et al, ASH 2020, poster 1194 

  • Post clinical trials on PFS and OS (Pasquini MC et al., Blood Advances 2020)



Mehcanism of action 

Humanized and engineered anti-CD19 Ab 

Clinical Activity 

  • Median DoR for the full efficacy population was 43.9 months (95% CI: 26.1-not reached [NR]) 
  • For patients who reached a best response of CR, the median DoR was NR (95% CI: 43.9-NR) (Duell et al, Haematologica 2021)


Bispecific antibodies 

  • Blinatumomab (CD19xCD3) 
  • CD3 x CD20 
    • Ecoritamab 
    • Glofitamab 
    • Mosunetuzumab 
    • Odronextamab 
    • Plamotamab 
    • IGM 2323 
  • More to come… 

Open Questions 

  • Are some of these agents able to cure R/R DLBCL patients? 
  • Does CD19-directed therapy (tafa or lonca) influence CAR T efficacy? 
  • Will CAR T move in second line for ASCT-eligible patients? 
  • Will Polatuzumab move to first line? 
  • How will bispecifics integrate this field