Aggressive B-cell Lymphoma

Dr. Michael Jain — Moffitt Cancer Center
Presentation Summary

Treatment of aggressive B cell lymphoma (i.e. DLBCL) is rapidly changing.

  • Historically, patients receive R-CHOP at first diagnosis, then at relapse 2nd line platinum chemotherapy (i.e. R-GDP) followed by ASCT with curative intent.
  • Presentation focus on new randomized trials that may challenge current treatment paradigms.
  • POLARIX trial where R-Pola-CHP shows benefit over R-CHOP
Second line

3 CAR T trials where 2 show a benefit over platinum/transplant in 2nd line

  • CNS prophylaxis
    • Patients with diffuse B cell may be at risk of relapse in CNS. Is it possible to further reduce risk?
  • Speculation about [near] future treatment of aggressive B cell lymphomas
Panelist Discussions
Aggressive B Cell Lymphoma

Drs. Kuruvilla, Crump, and Anglin

  • 2nd line therapy for patients eligible for more aggressive approaches [in Canada]
  • CNS Prophylaxis – Canadian and International data
  • FLAIR Study – practice changing? What is needed to make that decision?
Supplementary Content
Spotlight on CAR T

Dr. Jain’s presentation is augmented by an additional speaker/panelist segment.

Dr. Fred Locke, also from Moffitt Cancer Centre joins Drs. Kuruvilla and Anglin to consider…

  • Nuances of ZUMA-7, TRANSFORM and BELINDA
  • Discussion will also touch on:
    • CAR T in rrMM, high risk MM, and AML
    • Off the shelf allogeneic CAR T
    • Importance of and what to look for in longer term follow-up

Indolent  Lymphoma

(Follicular and Mantle Cell)

Dr. Martin Dreyling — Medizinische Klinik III, LMU München
Presentation Summary
Follicular lymphoma

Update to ESMO/EHA therapeutic algorithm, Dreyling, Ann Oncol 2021

First line
FOLL12 Study (Luminari, ASH 2021)
R-chemo + R maintenance vs R-Benda+ R maintenance

First relapse

  • MAGNIFY (Lansigan F, et al. ASH 2021)

3rd line
Immunotherapy (Bispecifics in combination, CAR T-cells) have a place for rrFL high risk patients

  • Phase I/II GO29781 study (Morschhauser, ASH 2021)
  • ZUMA-5 (Neelapu et al. ASH 2021)
  • Current GLA (German Lymphoma Alliance) studies in 2022
Mantle cell lymphoma

First line: R-Chemo + R2 maintenance
Near future: R-Chemo + Ibrutinib
Post-BTK: CAR T-cells, Glofitamab, Pirtubrutinib

Panel Discussion

Drs. Dreyling, Prica, and Villa

Follicular Lymphoma
  • Discussion on maintenance
  • Approach[es] to early relapse FL
  • R2 – Role and [potential] placement
  • Discussion of the data on BiTEs and CAR T
Mantle cell
  • Discussion on high-risk disease
  • Younger patients – discussion on high-dose cytarabine + ICT
  • Older patients and use of R2
  • Discussion of the data on BiTEs and CAR T

Multiple Myeloma

Dr. Keith Stewart — Princess Margaret Cancer Centre
Presentation Summary
  • No role for routine screening
Risk stratification in MM
  • Chromosome 1 abnormalities important
  • Update on drug regimens that show deep response and should be considered for high risk NDMM
  • Dara-Len Dex should be considered standard for non-SCT NDMM
  • Len remains standard maintenance
  • High risk MM remains a challenge
  • Treatment for Myeloma is being further disrupted with a number of new agents that show significant activity in heavily pre-treated
    • Immunotherapies, especially CART provide durable responses
    • Bispecifics are well tolerated and effective
    • Venetoclax and Iberdomide are very effective
  • ANDROMEDA study update
Panel Discussion

Drs. Chen, Stewart and Anglin

  • MGUS screening
  • Risk stratification and chromosome 1
  • Transplant ineligible
  • 4 drug+ induction regimens
  • LEN refractory disease in 2022
  • MRD directed therapy as per Masters
  • CAR T and BiTEs
  • VEN and t(11:14)

Acute Myeloid Leukemia

Dr. Charles Craddock — Queen Elizabeth Hospital
Presentation Summary
  • MAG/Ven/AZA appears promising triplet both in terms of response and toxicity
  • There are a number of other emerging agents where the data presented at ASH is too limited to permit even tentative conclusions
  • Remember that allo-SCT is essentially the only curative option in elderly AML
  • The definition of elderly AML is evolving. Is it…
    • patients > 60 years?
    • patients not fit for transplant?
    • patients not fit for intensive chemotherapy?
  • The agents emerging for management of patients not fit for intensive chemo are likely to play an increasingly important role in (A) and (B) as follows:
    • Preferable option to DA induction chemotherapy in older patients with an adverse karyotype
    • By improving transplant outcome – either by optimizing pre-transplant MRD status or as maintenance strategy
Panel Discussion

Drs. Richard-Carpentier and Schuh

  • First Line – CPX351 and comparison to HMA+VEN
  • Induction – VEN+AZA
  • First remission – QuAZAR-001 (oral AZA)
  • Older/unfit, high risk and rrAML – AZA+VEN+Magrolimab
  • Targetable mutations – FLT3, IDH1, as well as early-stage trials on other targets
  • Allogeneic Transplant

Hodgkin Lymphoma

Dr. Alison Moskowitz — Memorial Sloan Kettering
Presentation Summary
  • In advanced stage disease: survival benefit for BV-AVD in ECHELON-1
  • In bulky disease: ABVD x6 often sufficient, RT can typically be avoided
  • Relapse disease: anti-PD-1 +chemo combinations with high CR rates
Looking ahead
  • High potential for anti-PD-1 blockade to be integrated into front-line
  • Emerging role for CAR-T and anti-PD-1 combinations in R/R disease
Panel Discussion

Drs. Crump, Hodgson, and Kuruvilla

  • How to/where to incorporate the multi-approaches to HL
  • Ongoing trials for front line and high risk and potential impact
  • rrHL – incorporating novel inhibitors and potential use of radiotherapy
  • CCTG study – 2nd line standard vs combo Pembro+BV in transplant eligible

Chronic Lymphocytic Leukemia

Dr. Anthony Mato — Memorial Sloan Kettering
Presentation Summary

BTK inhibitors and CIT 

  • Ibrutinib is more effective than CIT as frontline therapy for CLL, including those with high-risk disease (deletion 17p and unmutated IGHV)  
    • FCR is equally effective for mutated IGHV 
  • CIT (FCR) is associated with increased risk of secondary cancers 
  • Use of BTKi is associated with increased cardio-vascular risk over time. 
    • Newer and potentially safer BTKi’s are on the horizon (i.e. acalabrutinib and zanubrutinib) 

BCL2 inhibitors 

  • Venetoclax/obinutuzumab-based fixed-duration frontline combinations can result in high rates of MRD eradication 

Trials covered: Long-term results of A041202, FLAIR, SEQUOIA, GHIA, CAPTIVATE and GLOW  

Relapsed/Refractory CLL – focus on BTK resistance
  • About half of patients discontinue frontline or salvage Ibrut, either due to resistance or intolerance 
    • VEN is the most effective standard option for these patients, but remission duration is limited 
    • Novel inhibitors are being developed for BTK resistance 
      • Pirtobrutinib is a novel experimental BTKi (including in patients with C481S mutation) 
      • PI3K inhibitors could be used in the future to consolidate patients 

 Trials covered: Addition of Ublituximab and Umbralisib (U2) to Ibrut, BRUIN, MK-1026 

  • COVID19 booster is recommended for CLL patients treated with biological therapy 
  • Both anti-CD20 monoclonal antibodies and BTK/BCL2 inhibitors significantly impact immune response to COVID19 vaccination 
    • A 3rd dose of vaccine (booster) can increase immunity in these patients 
Panel Discussion

Drs. Mato, Banerji, Chen, and Anglin

  • Cardiac assessment/screening and monitoring of patients on BTKi
  • Upfront therapy in high-risk disease (del17p, TP53)
  • CAPTIVATE Trial and combo therapy
  • MRD negativity and testing
  • Pi3K inhibitors
  • COVID and boosters

Thank You To Our Sponsors!