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.

Frontline

• 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

Other

• 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

• 2^nd 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

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

Relapse
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

Presentation Summary

MGUS

• No role for routine screening

Risk stratification in MM

• Chromosome 1 abnormalities important

NDMM

• 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

rrMM

• 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

Amyloidosis

• 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)

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

Presentation Summary

Today

• 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

Presentation Summary

Frontline

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 

CLL and COVID

• 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)
• VEN+OBIN
• CAPTIVATE Trial and combo therapy
• MRD negativity and testing
• Pi3K inhibitors
• COVID and boosters

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