Topline Presentation Points 

Treatment today in Canada
Frontline
  • Chemoimmunotherapy (FCR for young and fit – CLL8, BR for older and fit *some provinces – CLL10, CLB-O for older/unfit – CLL11)
  • BTKi – ibrutinib for older/unfit or just high risk [del(17p) and unmutated IgHV] – RESONATE-2, ECOG 1912
  • Increasingly broad indication/funding for BTKi means better disease control for patients but increasing costs (indefinite use of expensive, novel therapy) and adverse event management
  • Lots of interest in time-limited therapy (VO soon to come – CLL14)
Relapsed/refractory
  • Ibrutinib most commonly used agent (post-CIT)
  • VenR has increasing popularity or ven mono post-BTKi failure
Key News This Year

ELEVATE R/R – Head-to-head trial of acalabrutinib vs ibrutinib
Byrd J et al, ASCO 2021; Hillmen P, et al EHA 2021

  • Acalabrutinib Non-inferior to ibrutinib (IRC-Assessed PFS) with less adverse events than ibrutinib
    • Of note all grade atrial fibrillation significantly lower with acala

ALPINE – Phase 3 Randomized Study of Zanubrutinib vs Ibrutinib in Patients with rrCLL or SLL
Hillmen P et al, EHA 2021

  • Interim analysis suggests zanubrutinib has superior response rate, improved PFS, and lower afib vs ibrutinib)

GLOW – Phase 3 Study of Ibrutinib+Venetoclax in 1st line CLL
Kater AP et al, EHA 2021

  • With a median follow up of 27.7 months, IRC-assessed PFS for I+V was superior to Clb+O
  • I+V reduced the risk of progression or death by 78% vs Clb+O
  • PFS by investigator assessment was consistent with IRC
Key News out of ASH 202
Frontline

ASH Abstract 71- 1st line fit (FCR/BR, RVe, GVe, GIVe)

A Randomized Phase III Study of Venetoclax-Based Time-Limited Combination Treatments (RVe, GVe, GIVe) Vs Standard Chemoimmunotherapy (CIT: FCR/BR) in Frontline Chronic Lymphocytic Leukemia (CLL) of Fit Patients: First Co-Primary Endpoint Analysis of the International Intergroup GAIA (CLL13) Trial
Eichhorst et al.

  • GVe better than CIT in terms of uMRD at 15mo, 86.5% vs 52 %
  • Rve not better than CIT (57%)
  • GIVe not better than GVe and more fatal AEs

Additional Presenter Perspective: VO looks like most effective therapy for young and fit patients.

ASH Abstract 642– 1st line fit (FCR vs IR)

Ibrutinib Plus Rituximab Is Superior to FCR in Previously Untreated CLL: Results of the Phase III NCRI FLAIR Trial
Hillmen et al.

  • Median PFS not reached for IR and 67 mo for FCR
  • No statistical difference in PFS for mutated IgHV patients
  • NO DIFFERENCE in OS.

Additional Presenter Perspective: Perhaps a difference in OS in unmutated patients?

ASH Abstract 639- Long term follow-up on ALLIANCE

Long-Term Results of Alliance A041202 Show Continued Advantage of Ibrutinib-Based Regimens Compared with Bendamustine Plus Rituximab (BR)
Woyach et al.

  • Compared BR to ibrutinib (+/- R) 1st line
  • No difference in OS still
  • Most benefit of I+/- R in patients with TP53 abnormality
    • NO DIFFERENCE in those groups from those with TP53 wildtype

ASH Abstract 396- 1st line older (BR vs zanubrutinib)

SEQUOIA: Results of a Phase 3 Randomized Study of Zanubrutinib versus Bendamustine + Rituximab (BR) in Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Tam et al.

  • Median f/u 26 mo
  • PFS better for zanu than BR
  • No difference in OS