Topline  Presentation Points

Standard Practice in 2021 

  • Triplets in newly-diagnosed patients: RVD/KRD/VCD ¹ ² ³
  • Transplant and maintenance SOC⁴ 
  • Daratumumab initially approved in 2015 in patients with ≥3 prior lines of treatment  
    • Now approved in first line with VMP⁵ Dara-Rd with Rd (MAIA)⁶ 
    • Ongoing trials comparing and Dara-RVd vs RVd (GRIFFIN) 
  • Triplets such as KRd or PVD > doublets⁷  
  • Quadruplets are under investigation 
  • Continuous therapy is the accepted treatment paradigm for myeloma 
  1. Richardson PG, et al.Blood. 2010;
  2. Durie BGM, et al.Lancet. 2017;
  3. Jakoboviak A, et al. Blood. 2013;
  4. McCarthy A. N Engl J Med. 2015;
  5. Mateos MV, et al. N Engl J Med. 2018;
  6. Facon T, et al. N Engl J Med. 2019;
  7. Stewart AK, et al. N Engl J Med. 2015;
  8. Richardson PG, et al. ASCO. 2018.

BCMA-Targeted Immunotherapy in MM 

ADC Antibody drug conjugates 

A new class of treatment for multiple myeloma (MM), delivering potent cytotoxic agent directly to the myeloma cell. The target is defined by the specificity of the monoclonal antibody, which is linked to the cytotoxic agent. 

  • DREAMM-2, phase II study of belantamab mafodotin 
    • Accelerated approval in August 2020 
    • Ocular toxicity with belantamab mafodotin: keratopathy 
      (Lonial S et al. Lancet Oncol. 2020)

CAR T  

  • Chimeric antigen receptors (CAR) and CAR-T technology 
  • Anti-BCMA CAR T-cell therapy achieves deep responses in relapsed/refractory multiple myeloma 
  • Multiple anti-BCMA CAR T-cell therapies in clinical trials, presented at recent meetings  
  • Main differences relate to how they bind to BCMA, manufacturing 
    • Too early to know which one is better 
    • Different stages in clinical development 
  • KarMMa Trial, Ide-cel 
    • One treatment followed by observation:  “one-and-done” 
    • Ide-cel approved in March 2021
      (Munshi NC et al., ASCO 2020)
  • CARTITUDE-1 Trial, Cilta-cel 
    • Promising responses and PFS, but awaiting further follow up of “late” neurotoxicities 
      (Deepu Madurri et al, ASH 2020)
  • A different approach:  ALLO-715, ”off-the-shelf” allogeneic CAR T-cells;  cells manufactured from healthy donors
    (
    UNIVERSAL Study)

BiTE (bispecific antibodies) 

  • Five anti-BCMA bispecific antibodies presented at ASH 2020 
  • Promising responses in patients with ”triple-class exposed” disease, with associated CRS toxicities 

What’s next 

  • Mechanisms of resistance to anti-BCMA CAR T cell therapy 
    • CAR-T cell in vivo expansion and persistence 
    • T-cell fitness is important in CAR T-cell treatment 
  • Strategies to overcome T-cell fitness 
    • BCMA loss or downregulation has been described after anti-BCMA CAR T cell therapy 
    • Strategies to overcome – dual targeting strategies  
    • BCMA and TACI as targets in multiple myeloma 
  • Other MM target antigen candidates for CAR T cell therapy 
    • GPCR5D, FcHR, CD38, CD138, SLAMF7 
  • Opportunities for combination treatment: biological rationale