Presentation Summary

Review recent CLL presentations with practice implications for Canada including:

• RESONATE-2: 8 year update (IBR vs CLB in older).
• ECOG 1912: 5 year update (FCR vs IR in young and fit).
• CLL13 GAIA: (FCR/BR vs VR vs VO vs IVO in young and fit).
• CLL14: 5 year update (VO vs CLB-O).
• ELEVATE-TN: 5 year update (A vs AO vs CLB-O).
• BRUIN: update (pirtobrutinib).

Discuss how to incorporate this information into current Canadian practice.

Key Takeaways:

• Aim to see VO funded in young and fit CLL patients soon.
• For now, while FCR may not be ‘popular’, is still an acceptable option for good risk (mutated IgHV) patients.
• Need to carefully watch the SPM rates for ven-based frontline therapies (and BTKi).
• Still no indication to add obinutuzumab to acalabrutinib but need to watch longer term data to determine if there is a group of patients where this should be done.
• Pirtobrutinib soon to enter Canada at least through clinical trials.

cHL

FIRST-LINE BRENTUXIMAB VEDOTIN PLUS CHEMOTHERAPY IMPROVES OVERALL SURVIVAL IN PATIENTS WITH STAGE III/IV CLASSICAL HODGKIN LYMPHOMA: AN UPDATED ANALYSIS OF ECHELON-1

• A+AVD is the first regimen to show an improvement in OS versus classic ABVD in untreated advanced cHL
• A+AVD should be considered the preferred first-line treatment option for patients with previously untreated stage III or IV cHL

Mantle Cell Lymphoma

Phase III SHINE Study of Ibrutinib in Combination With Bendamustine-Rituximab and Rituximab Maintenance as a First-Line Treatment for Older Patients With Mantle Cell Lymphoma

• SHINE is the first phase 3 study supporting that ibrutinib in combination with standard chemoimmunotherapy is highly effective in patients with untreated MCL
  • Median PFS of 6.7 years: a highly significant and clinically meaningful 2.3-year PFS advantage
  • Sets a new benchmark for first-line treatment regimen in older patients with MCL who are unsuitable for ASCT

Long-term Follow-up of ZUMA-2 in Relapsed/Refractory MCL

• 3-year ZUMA-2 follow-up data demonstrate that a single rate of KTE-X19 resulted in high rates of durable responses in R/R MCL
• MRD negativity may predict for a longer response duration

DLBCL

Evolving Management of R/R DLBCL

• Novel Agents Recently Approved in R/R DLBCL
  • Pola-BR, Selinexor, Tafasitamab/Lenalidomide
• Other CD20/CD3 Bispecific Antibodies in B-cell lymphomas
  • Odronextamab, Mosunetuzumab
  • Glofitamab – first T-cell-engaging bispecific monoclonal antibody to demonstrate clinically meaningful outcomes for patients with R/R DLBCL in a pivotal Phase II setting

LBCL

• Epcoritamab – first in class subcutaneously administered T-cell engaging bi-specific antibody. Deep and durable responses in hard to treat R/R LBCL

Waldenström macroglobulinemia

ASPEN: Long-term follow-up results of a phase 3 randomized trial of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia

• Zanubrutinib, with long-term follow-up, continued to demonstrate clinically meaningful efficacy in patients with WM
  • At median follow-up of nearly 4 years, 66% of patients remain on treatment with zanubrutinib versus 52% with ibrutinib
  • With longer follow-up, safety advantages of zanubrutinib remained consistent with less off-target activity compared with ibrutinib

Recent Updates in Acute Myeloid Leukemia

• New International Consensus Classification (ICC) of AML
• Updated 2022 European Leukemia Network (ELN) risk categorization for AML
• QuANTUM-First Phase 3 trial results (7+3 + Quizartinib in FLT3-ITD mut AML)
• Prognostic impact of Measurable Residual Disease before HSCT
• Characteristics of long-term survivors with oral azacitidine maintenance
• AGILE Phase 3 trial results (Azacitidine + Ivosidenib in IDH1 mut AML)
  • Azacitidine + Venetoclax in patients with IDH1-mut AML

Key Takeaways

• ELN 2022 and ICC: Refinement of the characterization of distinct AML subtypes with prognostic and therapeutic relevance.
• Many drugs approved for AML in the recent years. Almost all targeted drugs. We are now learning how to use them, combine them and integrate them in our evolving treatment algorithms.
• Foreseeable challenges in treatment decisions as more than one options might be available for a specific clinical situation.
• MRD monitoring in AML is becoming more widely accessible, but many challenges remain in regard to interpretation, standardization and actionability to improve patient outcomes.

Presentation Summary

• Updates to standard of care from a Canadian perspective
  • Therapy for limited stage
  • Therapy for advanced stage
    • Long term follow-up of 4 RCT ABVD versus BEACOPP
    • ECHELON 1 trial
• CADTH summary of funded options

Presentation Summary

• BCMA as a target in MM
  • CART and BiTes dominate oral sessions
  • Access for MM in Canada remains limited to trials
• Defining smoldering myeloma
  • Evaluating serum FLC ratio as a biomarker for (S)MM
• Newly diagnosed multiple myeloma (NDMM)
  • Phase 3 DETERMINATION trial
    • Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression
  • GRIFFEN (and CASSIOPEIA) explore additive benefits of CD138 Ab as a “quad” induction for ndMM transplant eligible
  • Phase 2 study IFM 2018-04
    • Daratumumab carfilzomib lenalidomide and dexamethasone as induction therapy in high-risk, transplant-eligible patients with newly diagnosed myeloma
• Post-SCT
  • Phase 3 ATLAS – carfilzomib, lenalidomide, and dexamethasone vs lenalidomide
• MRD
  • Role of MRD adapted strategies continue to be explored at this time particularly in the curative setting
    • Undetectable MRD in bone marrow is a good surrogate marker for cure
    • How we will utilize it going forward requires more study and work
• Algorithm for Canadian patient access May 2022
• What the future might look like

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