Outcomes for patients with CLL have improved considerably since the availability of inhibitors of B-cell signalling (BTKi and PI3Ki) and of anti-apoptotic proteins BCL2 (BCL2i). While fixed-duration combinations of BTKi and BCL2i have been recently evaluated, recent practice of utilisation is to sequence these therapies individually. However, the outcomes for patients who are refractory/resistant to both BTKi and BCL2i are poor. Standard of care use of PI3K has largely been relegated below covalent BTKi and BCL2i due to concerns about toxicity and inferior efficacy when used. Non-covalent BTKi (eg pirtobrutinib) demonstrate efficacy in C481 BTK-mutated CLL previously treated with covalent BTKi, however pirtobrutinib availability on compassionate access has generally been restricted to PI3K-exposed patients. We hypothesise that real-world survival outcomes are poor and rates of treatment discontinuation are high for double-refractory CLL patients treated with PI3K.

Objectives

• Primary:
  • DoR, PFS, TTNT, and OS from PI3Ki initiation
• Secondary:

1. 1. Rate of PI3Ki treatment discontinuation
   2. Describe AEs encountered
   3. Describe subsequent therapies upon progression/relapse

25 July 2023 – brief protocol and data collection tool circulated.

20 November 2023 – another appeal for expressions of interests/patients available from sites