The 11th Annual

Canadian Hematology Conference 2021 Report

Hematology

12 Nov 2021

DAY 2

October 1st 2021

Non-Hodgkin Lymphoma 1

Current and Novel Therapy in RR-DLBCL

Dr. Gilles Salles, Memorial Sloan Kettering Cancer Center

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Presentation Summary

Relapsed and refractory DLBCL: Current Status

Emerging agents: 

  • Antibody drug conjugates
  • Selinexor
  • Tafasitamab
  • Bispecifics antibodies
  • Cellular therapies
    • Brex-Cel
    • Axi-Cel
    • Tisa-cel

    Key Takeaways and Open Questions 

    • In 3 years, 7 new agents approved by FDA for R/R DLBCL 
    • As of today, the following are approved in second line in transplant ineligible patients 
      • Polatuzumab Vedotin + BR (2nd line in EU & Canada; 3rd line in US) 
      • Tafasitamab – Lenalidomide (US & EU) 
      • All other agents are so far approved in 3rd line 
      • No randomized comparison exist between these options… but recent data suggest: 
        • CAR T provides a better benefit than Pola-BR
          (Avivi et al; EHA 2021)
        • Tafa-Len provides a better benefit than R-Gemox and other options
          (Nowakowski et al, SOHO 2021)
    • 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 be integrated into this field
Central Nervous System Prophylaxis in DLBCL

Dr. Christopher Fox, Nottingham University Hospitals

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Presentation Summary

Why worry so much about CNS prophylaxis? 

  1. CNS relapse is a devastating event with poor outcomes for the majority 
  2. Accurately identifying patients at risk of a CNS event is difficult. Need better tools to identify the ‘who’… 
  3. It remains unclear how best to mitigate against the risk of CNS relapse 
  4. Prophylactic interventions confer risks of additional toxicity 

What do I do in clinical practice (Q4 2021..)?

Who?

  • Focus on ‘highest risk’ patients – testicular/renal/adrenal/CNS-IPI (4),5-6 and/or ≥3 EN sites.
  • Careful and balanced discussion regarding the uncertainties

When?

  • Typically EOT (PET CMR)
  • Consider CSF and MRI at baseline to ‘exclude’ occult CNS disease 

How?

  • HD-MTX 3.5g/m2 over 3 hours, 2x infusions q14-21 

CNS prophylaxis: a look to the future…..  

Who?

  • A large (retrospective) dataset anticipated at ASH 2021 – will this be sufficient to inform practice?
     
  • Efforts must focus on validating biomarkers to accurately characterize a very high risk group 

When?

  • A (separate) large (retrospective) study anticipated at ASH 2021 (EOT vs intercalated HD-MTX) 
  • CSF biomarkers +/- neuroimaging studies may inform the question on who and when 

How?

  • Impact of more effective systemic DLBCL regimens deserves attention
  • CNS-active agents beyond HD-MTX warrant investigation as prophylaxis 

When prophylaxis fails… 

  • Rationale for the Phase II MARIETTA trial (IELSG42)
    (Ferreri AJMF et al, Lancet Haematology 2021)
Management of Frontline PTCL

Dr. Steven M. Horwitz, Memorial Sloan Kettering Cancer Center

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Presentation Summary

  •  [Peripheral T-cell lymphoma (PTCL) remains heterogeneous and poor prognosis,  
    • OS varies according to subtype and median ranges from 1-3 yr 
    • Therapy most often CHOP
      Vose. J Clin Oncol. 2008;26:4124

However: 

  • Cures for some with combination chemotherapy
    • BV-CHP, CHOP/CHOEP, ASCT 
  • Prognostic factors can impact decision making 
    • Pretreatment-Subtype, Mutational profile? 
    • On treatment-interim response 
  • Attempts to incorporate into combination/upfront/curative therapy 
    • Active agents 
    • Enriched population 
    • Subtype specific strategies: 
      • Disease subtypes, molecular subtypes, other
The Role of Radiation in Diffuse Large B-Cell Lymphoma in 2021

Dr. Danielle Rodin, Princess Margaret Cancer Centre

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Presentation Summary

Current Indications 

  • Upfront Consolidation 
  • Relapsed/Refractory 
    • Peri-transplant 
    • Bridging with CART 
  • Salvage and Palliation 
    • Symptom Control 

Radiotherapy Decision-Making Considerations 

  • Disease 
    • Indications (alone, consolidation, salvage, palliative) 
    • Overall prognosis 
  • Patient 
  • Site 
    • Organs at risk 
    • Organ motion/filling 
    • Set-up reproducibility 
  • Dose
    • Total and daily 
  • Treatment Volume 
    • Size, distance to organs at risk 
  • Treatment technique  
    • 3D-conformal, IMRT, VMAT 
    • Photon vs proton 
  • Side effects 
  • Risk-benefit  assessment 

Individualizing the Benefit 

  • PET in Early-Stage Disease 
    • LYSA/GOELAMS 02-03 Trial (France)
      (Lamy et al: Blood. 2018 Jan 11; 131(2): 155–156)
  •  PET-Directed RT: Elderly Patients with Bulk 
    • OPTIMAL>60 
      (Pfreundschuh M, et al. J Clin Oncol 2017; 35 (15_suppl): 7506.)
  • Applying these trials to practice

New Frontiers: Relapsed and Refractory 

  • Bridging Radiotherapy with CART 

Chronic Lymphocytic Leukemia

Treatment of CLL – From a Canadian Perspective

Dr. Versha Banerji, Cancer Care Manitoba

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Presentation Summary

Frontline therapy of CLL patients in Canada  

  • Use best agent upfront which is informed by  
    • Age, Fitness and Kidney Function,  
    • CADTH Provisional Funding Algorithm Diagram for CLL 
    • [Select] Trial data add further context (ECOG 1912, CLL14, ELEVATE-TN, ALLIANCE) 
    • Algorithm based evidence and updates from Canadian Cancer Trial Group 
Dr. Anthony Mato
State of the Art Management in Relapsed Refractory CLL

Dr. Anthony Mato, Memorial Sloan Kettering Cancer Center

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Presentation Summary

(Click Image to Enlarge)

Presentation Points 

Five targeted agents approved in the R/R setting 

  • potential sequences in the R/R setting = 120 sequences 
Frontline CLL

Dr. Susan O’Brien, UC Irvine

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Presentation Summary

  • For mutated IGHV pts who need 1L therapy, FCR (younger, fit pts), BR, or Chl/Obin (older, frailer patients) remain reasonable options
  • Unmutated IGHV pts should generally not receive chemoimmunotherapy
     
  • BTKi +/- obin is an excellent continuous therapy option 
  • Venetoclax + obin is an excellent time-limited therapy option
  • BTKi + BCL-2i is a promising new approach, but not yet standard of care
  • Active participation in clinical trials remains critical 

Non-Hodgkin Lymphoma 2

Current and Novel Therapy in RR-FL

Dr. Sonali Smith, University of Chicago Medicine

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Presentation Summary

FL remains important cause of death 

Options in the relapsed/refractory setting: NO DATA ON SEQUENCING 

  • Chemo/autoHCT 
  • AlloHCT 
  • Radioimmunotherapy (ibritutumomab tiuxitan) 
  • Immunomodulatory agents  
  • PI3K inhibitors  
  • EZH2 inhibitors 
  • CAR-T 
  • Bispecific antibodies, clinical trials** not approved
CAR T-cell Therapy: Mantle Cell and Follicular Lymphoma

Dr. Caron Jacobson, Dana Farber Cancer Institute

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Presentation Summary

  • CD19 CAR T-cells have activity across B-NHL histologies and can lead to a high rate of durable remissions in mantle cell lymphoma and indolent B-NHL 
    • Toxicity appears to be the same or better than in aggressive B-NHL 
      • Similar for MCL and MZL 
      • Improved for FL 
  • Longer follow-up is needed to understand if these responses represent cures in these historically incurable malignancies 

 

  • Ongoing Studies 
    • Mantle cell lymphoma 
      • TRANSCEND NHL 001 (Liso-cel) 
      • ZUMA-2 Cohort 2: relapsed MCL pre-BTK inhibition (Brexu-cel) 
    • Indolent B-NHL 
      • ZUMA-5 in marginal zone lymphoma (Axi-cel) 
      • ELARA (Tisa-cel) 
      • TRANSCEND FL (Liso-cel) 
    • Phase 1/2 studies of new products: allo and NK CAR, dual antigen targeting CARs 
Maintenance Therapy in Indolent Lymphoma

Dr. Diego Villa, BC Cancer

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Presentation Summary

Maintenance therapy in indolent NHL 

  • Systemic therapy administered to patients responding to a course of therapy (typically chemoimmunotherapy) with the goal of prolonging the duration of response.
  • Can be given as part of any line of therapy.
  • Typically given for a prolonged period of time at doses and schedules generally less intensive than the induction therapy.
  • Maintenance rituximab (MR) is the most common form.  
    • Others: 
      • Other CD20 monoclonal antibodies (ie, Obinutuzumab) 
      • Oral agents that can be given on a continuous basis (ie, lenalidomide, BTK inhibitors, PI3K inhibitors)