Chronic Lymphocytic Leukemia

Dr. Carolyn Owen – University of Calgary

About Speaker

Dr. Carolyn Owen – University of Calgary

Dr. Carolyn Owen is an Associate Professor in the Division of Hematology & Hematological Malignancies at the University of Calgary. She completed internal medicine training in Ottawa, Hematology training in Vancouver followed by a research fellowship in molecular genetics at Barts and the London School of Medicine in London, UK. Her prior research is focused on familial myelodysplasia and acute myeloid leukemia. Her current clinical interests are low grade lymphoma and chronic lymphocytic leukemia and she is the local principal investigator at the Tom Baker Cancer Centre for several clinical trials in these areas.

CLL Highlights from ASCO and EHA 2021

First results of a head-to-head trial of acalabrutinib (acala) versus ibrutinib (Ib) in previously treated chronic lymphocytic leukemia.

ASCO 2021 Abstract 7500. Byrd et al.
EHA 2021 Abstract S145. Hillmen et al.

Results Highlights:

  • At a median follow-up of 40.9 months (range 0.0–59.1), acala was noninferior to Ib with a median PFS of 38.4 months in both arms (HR 1.00; 95% CI 0.79–1.27).
  • Tolerability profiles for acala and Ibr are different:
    • Among any-grade adverse events occurring in ≥20% of patients in either arm, acalabrutinib was associated with a lower incidence of hypertension (9.4%, 23.2%), arthralgia (15.8%, 22.8%), and diarrhea (34.6%, 46.0%) but a higher incidence of headache (34.6%, 20.2%) and cough (28.9%, 21.3%).

Key Takeaway:

  • ELEVATE-RR demonstrated reduced rates of cardiac toxicities with acalabrutinib over ibrutinib with no difference in efficacy

This trial and the impact it may have on practice was discussed in more depth by Drs. John Kuruvilla, Peter Anglin, Susan O’Brien, and John Pagel.

Click here to access the first segment of the CARE™ CLL Discussion Series:

First Interim Analysis of Alpine Study: Results of A Phase 3 Randomized Study Of Zanubrutinib Vs Ibrutinib In Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

EHA 2021 Abstract LB1900. Hillmen et al.

Results Highlights:

  • Superior PFS with zanubrutinib vs ibrutinib (figure.)
  • Significantly less afib and less bleeding and less AEs leading to discontinuations or deaths

Key Takeaway:

  • The ALPINE study demonstrates improved tolerability and efficacy of zanubrutinib over ibrutinib suggesting there could be a role for this BTKi in the future.
Primary Analysis of The Fixed-Duration Cohort from The Phase 2 Captivate Study of First-Line Ibrutinib (Ib) + Venetoclax (Ven) For Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

ASCO 2021 Abstract 7051. Ghia et al.
EHA 2021 Abstract S147. Allan et al.

Results Highlights:

  • 24-month PFS and OS rates were 95% and 98%, respectively.
    • Similar results were achieved in patients without del(17p) (n=136) 
  • The most common grade 3/4 AEs were neutropenia (33%), hypertension (6%), and decreased neutrophil count (5%).

Key Takeaway:

  • First-line Ibr + Ven is an all-oral, once-daily, chemotherapy-free fixed-duration regimen that provides deep, durable responses in patients with CLL/SLL.
Fixed-Duration Ibrutinib and Venetoclax (IV) Versus Chlorambucil plus Obinutuzumab (Clb+O) for First-Line (1l) Chronic Lymphocytic Leukemia (CLL): Primary Analysis of the Phase 3 GLOW Study

EHA 2021 Abstract LB 1902. Kater et al.

Results Highlights:

  • At end of therapy, uMRD in bone marrow was 52%; in peripheral blood it was 55%
  • 84.5% of patients were maintained at end of treatment (+ 12 months)
  • OS not different between arms at current median follow-up of 28 months

Key Takeaway:

  • GLOW demonstrates efficacy of IV – an all oral, fixed duration regimen which will add yet another highly effective treatment option for front line CLL in Canada
Up to seven years of follow-up in the RESONATE-2 study of first line ibrutinib treatment for patients with chronic lymphocytic leukemia.

ASCO 2021 Abstract 7523. Barr et al.

Results Highlights:

  • At 6.5y, PFS was 61% in pts treated with ibrutinib vs 9% in pts treated with chlorambucil.
    • This PFS benefit was observed across all subgroups
  • Responses continue to deepen over time.
    • ORR was 92% for ibrutinib-treated pts with complete response (CR/CRi) rate increasing to 34% with this follow-up.
  • Ibrutinib remains well tolerated with no new safety signals observed

Key Takeaway:

  • Extended long-term data from RESONATE-2 demonstrate the sustained PFS and OS benefit of first-line ibrutinib treatment for pts with CLL, including for pts with high-risk genomic features.
Other Key CLL News from 2021:
  • PCODR conditionally approved funding of acalabrutinib (second generation BTKi) and venetoclax + obinutuzumab in Canada (in non-fludarabine eligible patients).
    • Funding remains variable across the country, but it is anticipated that these will become standard options in first line moving forward.
  • PCODR approved acalabrutinib for r/r CLL.

Thank you to our CARE™ at ASCO/EHA Sponsors