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)

Selinexor:

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)

 

Tafasitamab  

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