Topline Presentation Points

Follicular lymphoma snapshot: outcome after relapse 

  • Median survival for follicular lymphoma approaches 20 years, but… 
  • PFS and OS decline with each subsequent relapse 
  • Early relapse (POD24) predicts 5 yr OS of 50% 

FL remains important cause of death 

FL: Clinical categories and treatment options 

Chemoimmunotherapy in rel/ref FL 

  • Benda-based regimens yield med PFS 2 years  
  • Can BR/BO be backbone for more agents?  

Immunomodulatory agents 

AUGMENT RP3 Len-ritux vs. Placebo-ritux  

  • Lenalidomide in relapsed (not refractory) FL:  
    • Results (R2 only):  
      • Med PFS 39.4m (vs. 14m for R-pbo) 
      • ORR 78%, CR 34% (Andorsky DOI: 10.1200/JCO.2019.37.15_suppl.7513 Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 7513-7513)
  • MAGNIFY 
    • Phase IIIb interim analysis of induction R2 
    • OR 73% CR 45%

      (Leonard J Clin Oncol 2019 May 10;37(14):1188-1199)
  • Will obinutuzumab offer incremental benefit and superiority?

 

PI3K inhibitors in rel/ref FL 

  • Three agents FDA-approved – Idelalisib, Copalisib and Duvelisib 
    • All tested in heavily pretreated, refractory patient population  
    • Median OS for idela and duvelisib approximately 2 years (more refractory disease)  
    • Low CR rates  
    • Toxicity (not discussed) is a limitation for combination therapy for some agents

Salles Haematologica 2017 Apr;102(4):e156-e159; Dreyling Ann Oncol 2017 Sep 1;28(9):2169-2178;  

Flinn J Clin Oncol 2019 Apr 10;37(11):912-922 

 

  • Umbralisib: new PI3Kd and CK1e inhibitor (FDA approved 2021) 
    • More selective for PI3Kd 
    • Inhibits CK1e (Treg modulation)(Burris Lancet Oncol 2018 Apr;19(4):486-496)
      (Umbralisib in rel/ref indolent lymphomas)
    • Single arm trial (n=208) 
    • RR FL, MZL, SLL 
    • N=117 with FL 
    • DOSE: 800mg orally daily 
    • ORR 45% (CR 5%)(Fowler J Clin Oncol 2021 May 20;39(15):1609-1618)

EZH2 Inhibitor 

  • Tazemetostat monotherapy in rel/ref FL  
    • demonstrated durable, single-agent, antitumor activity in R/R FL patients with activating mutations (MT) or wild-type (WT) EZH2  
  • Open label phase II trial:   

(Morchhauser ASH 2019) 

CAR T 

  • ZUMA-5 Axi-cel 
    • March 2021 approved r/r FL with > 2 lines of therapy (Jacobson ASH 2020 Abstract 700) 
  • ELARA: Tisa-cel in r/r FL 
    • Promising safety profile 
      • Comparing cytokine release syndrome and neurotoxicity 
        • In ELARA trial most CRS (75%) and all neurotoxicity (100%) occurred in patients with bulky disease

Schuster ASCO 2021 Abstract 7508: Efficacy and safety of tisagenlecleucel (Tisa-cel) in adult patients (Pts) with relapsed/refractory follicular lymphoma (r/r FL): Primary analysis of the phase 2 Elara trial 

  • Which indolent lymphoma patients should be considered for CAR-T? 
    • Patient identification is key! 
      • The vast majority of patients with FL do well without aggressive treatments  
      • Disease characteristics 
        • early POD, double refractory, multiple prior regimens with sequentially shorter PFS 
      • Patient characteristics 
        • No upper age limit, adequate cardiac/renal/pulmonary/neurologic reserve  
      • Bulky disease and need for bridging therapy are poor prognostic factors  
    • No clear difference between axi-cel and tisa-cel in terms of efficacy in FL 
    • Marginal zone lymphoma needs more data  

Emerging class of agents: bispecific antibodies 

  • Odronextamab 
  • Glofitamab 
  • Mosunetuzumab 
  • Epcoritamab