Topline  Presentation Points

PTCL Entities by Therapeutic Strategy 

  • CHOP based therapy Reasonable 
    • PTCL-NOS 
    • AITL (angioimmunoblastic) 
    • Follicular T-cell lymphoma 
    • Nodal PTCL with TFH phenotype 
    • ALCL, ALK-positive 
    • ALCL, ALK-negative 
    • Enteropathy-associated TCL 
    • Monomorphic epitheliotropic intestinal T-cell lymphoma 
  • Where CHOP is reasonable, are there ways to improve upon it? 
    • Dose intensification 
      • Possible improvement with addition of etoposide
        German Prospective High-Grade NHL Studies (Schmitz N, et al. Blood. 2010;116:3418-3425.)
  • Upfront Transplant in PTCL (d’Amore F et al. J Clin Onc. 2012;30:3093-3099)
  • Adding to a CHOP backbone-BV in untreated PTCL 
    • ECHELON-2 (Brentuximab Vedotin) (Horwitz S et al. Lancet. 2019; 393:229-240)
      • ALCL 
        • BV-CHP-Overall survival benefit 
        • standard of care
      • PTCL-NOS, AITL 
        • Part of ITT-on label in US 
        • Subset size precludes statistical conclusions 
          • BV-CHP and CHOEP-might be better than CHOP 
          • Imperfect datasets 
      • Consolidation with ASCT-appearsto still add benefit 
      • Other prognostic factors DUSP22, tp63 
    • Adding an active drug to CHOP AND Enriching for those most likely to benefit can be successful 
    • Median OS of CHOP not met at 5 yrs 
      • Echelon-2 Trial 5-Year Results: PFS (INV Assessment) and OS

        (
        Horwitz et al ASH 2020 a1150)
  • Further Refining Chemotherapy Based Strategies – Who Benefits? 
    • Maximalist chemotherapy approaches in PTCL-Combo chemo-ASCT   
      • Can mutational profiling prospectively identify those who are more or less likely to benefit from this approach 
        • ALK-1 
        • DUSP22 
        • TP53 
        • DNMT3A 
        • TP63 
    • Goal-identify those likely cured with standard approaches vs those who need completely alternative approaches 
  • Other Targeted Approaches? 
    • Genetic Drivers in Subtypes and Subgroups of PTCL 
      • AITL and TFH subtypes of PTCL enriched for mutations in epigenetic modifiers: TET2, DNMT3A, RHOA, IDH2 
      • TFH Phenotype Predicts Response to HDAC Inhibitors and Azacytidine in Relapsed/Refractory PTCL 
        • Romidepsin Plus CHOP in Patients with Previously Untreated PTCL 
          • Phase 3 study (conducted by LYSA) (Bachy E, et al. ASH 2020. Abstract 39.)
        • Oral Azacitidine (CC-486) Plus CHOP as Initial Treatment for PTCL 
          • Phase 2 study (Ruan J, et al. ASH 2020. Abstract 40.)
  • Upcoming Trial 
    • Alliance[b] 
      • Phase II study of adding duvelisib or CC-486 to usual treatment for PTCL