Topline Presentation Points 
FRONT LINE (1:12-5:17)

POLARIX Study at ASH 2021

  • Randomized clinical trial improving on frontline therapy with Polatuzumab Vedotin an anti-CD79b mAb with cytotoxic agent MMAE
  • Results of investigator-assessed PFS with Pola-R-CHP vs R-CHOP

Key Takeaways:

  • R-Pola-CHP demonstrates a PFS benefit over R-CHOP
  • Absolute risk reduction (2 year PFS) = 6.5% (NNT~15)
  • No difference in OS Safety is similar

CNS Prophylaxis (5:18-9:24)

Patients with diffuse B cell may be at risk of relapse in CNS. Is it possible to further reduce the risk?

Risk factors

  • IPI – age, performance status, LDH, extranodal disease, stage, plus kidney or adrenal involvement
  • Vast majority of patients had <7.4% risk of having a relapse in brain/CNS
  • Risk has been further decreased with Rituximab (R-CHOP)

Key Takeaways:

  • CNS relapse is an uncommon, but devastating occurrence after R-CHOP in DLBCL
  • High-dose Methotrexate (HD-MTX) has at best a small impact on preventing CNS relapse
  • IT- therapy may just as good as HD with less toxicity
  • [Dr. Jain has] personally stopped recommending it as an academic opinion outside of testicular

Second-line DLBCL (9:25-22:03)

Exciting news outside of standard of care pathway with CAR – T

  • ZUMA-7 (axi-cel vs SOC) Locke et al. NEJM 2021
  • TRANSFORM (liso-cel vs SOC) Kansas et al. ASH 2021
  • BELINDA (tisa-cel vs SOC) Bishop et al. NEJM 2021

Key Takeaways:

  • The 3 trials are slightly different with 865 total patients
  • Some trials had more/less bridging, some had more transplants but overall similar delivery of CAR T cells and crossover to CAR T cells on SOC arm

Tisa-cel vs axi-cel/liso-cel

  • Didn’t not perform as well and didn’t meet primary end point
  • Manufacturing not as reliable/quick on trial, although similar % of patients received CAR T
  • No explanation for results that is as simple Tisa-cel having lower efficacy

Axi-cel vs liso-cel

  • Liso-cel has less CAR T toxicity (CRS, neurotoxicity)
  • Follow-up for Liso-cel short, but appears to have good efficacy
  • For clinical selection consider:
    • manufacturing availability and success rates
    • Non-clinical trial “real world” data
    • Use of toxicity mitigation strategies (i.e. prophylactic steroids)
Speculation about [near] future treatment of aggressive B cell lymphomas (22:03 -24:20)

Currently approved therapies for DLBCL (In USA)

  • Polatuzumab – Bendamustine – Rituximab –
  • Tafasitinib (CD19 antibody) – Lenolidomide
  • Selinexor

Bispecific Antibodies – connect T cells to tumour

  • Non-randomized trials show similar efficacy to CAR T cell therapy with greater convenience and safety, longer treatment duration.
  • Combination trials (i.e. Polatuzumab) underway
  • Questions remain: long-term durable remission rates, “real world” outcomes, sequencing/combining with CAR T cell therapy are all unknowns

Improvements to CAR cell therapy

  • Targets: more targets and bispecific targeting
  • Engineering: better CAR activity, better trafficking, less susceptible to exhaustion
  • Cell selection: CAR-NK, CAR myeloid/macrophage, CAR gamma/delta T-cells, allogeneic cells
  • Clinical: combination therapy with other active agents, improved bridging