What factors influence BTKi + BCL-2i treatment selection for patients with CLL?

The Lymphoma Hub was pleased to speak to Francesc Bosch, Vall d'Hebron Barcelona Hospital Campus, Barcelona, ES. We asked, What factors influence Bruton’s tyrosine kinase inhibitor (BTKi) + B-cell lymphoma-2 inhibitor (BCL-2i) treatment selection for patients with chronic lymphocytic leukemia (CLL)?

Key points

• There are several treatment options for patients with CLL, with targeted therapy regimens broadly categorized as continuous or fixed-duration.
• Among the fixed-duration treatment strategies, there are three options comprising an anti-CD20 monoclonal antibody or BTKi combined with the BCL-2i venetoclax: obinutuzumab + venetoclax, ibrutinib + venetoclax, and acalabrutinib + venetoclax, the latter of which was recently approved by the European Commission.¹
  • Ibrutinib + venetoclax and acalabrutinib + venetoclax are also approved for use with the addition of an anti-CD20 monoclonal antibody in some countries in Europe.^1,2
• Current treatment algorithms favor the use of fixed-duration therapies over continuous therapy for several reasons:
  • Fixed-duration therapy reduces the overall costs and resource use.
  • Continuous therapy may increase the risk of resistance mutations.
  • Fixed-duration therapy is associated with lower long-term toxicity vs continuous therapy.
• Treatment algorithms within the Spanish Group for CLL and the European Society for Medical Oncology (ESMO) guidelines favor fixed-duration therapy with obinutuzumab + venetoclax or BTKi + venetoclax for first-line patients with CLL.^3,4
• Fixed-duration therapies are highly active in CLL, and currently, no direct comparison data of obinutuzumab + venetoclax and BTKi + BCL-2i have been published, making treatment decisions based on activity difficult.
• Other factors can be used to dictate the treatment strategy, such as comorbidities, ease of use, patient proximity to the hospital, and patient preferences.
  • The use of obinutuzumab can be complicated in smaller hospitals where there may be less experience in the management of infusion-related reactions.
  • The presence of cardiac comorbidities can prevent the use of BTKi.
• Continuous BTKi treatment is recommended for patients with high-risk genetics, as the impact of continuous BTKi vs fixed-duration therapy on overall survival remains unclear in these patients,^3,4 whereas fixed-duration therapy can be considered for most other patients with CLL.

Bosch concluded by suggesting that fixed-duration BTKi + BCL-2i can be used in the majority of patients, particularly in younger patients without cardiac comorbidities, or if the patient lives far away from the hospital and the management of obinutuzumab is complicated. For elderly patients, where BTKi can induce cardiac toxicity, fixed-duration obinutuzumab + venetoclax may be preferred. 

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