Chronic lymphocytic leukaemia: guideline history

Anchored to: FDA approvals of venetoclax plus obinutuzumab (May 2019, CLL14) and first-line acalabrutinib (November 2019, ELEVATE-TN)

• addedUntreated, all fitness levels: Fixed-duration venetoclax plus obinutuzumab (12 months) as a preferred first-line regimen.
• addedUntreated: Acalabrutinib with or without obinutuzumab as a preferred continuous regimen.

Anchored to: Annals of Oncology publication, 2021

• recategorisedUntreated, del(17p) or TP53-mutated: Chemoimmunotherapy no longer recommended for any patient with TP53 aberration; BTK inhibitor or venetoclax-based therapy required.chemoimmunotherapy for fit patients → targeted therapy only [I, A]
• addedUntreated, IGHV-unmutated: Targeted therapy preferred over FCR for IGHV-unmutated disease.

Anchored to: FDA approval of zanubrutinib for CLL (January 2023, ALPINE and SEQUOIA) and pirtobrutinib after BTK and BCL-2 inhibitors (December 2023); withdrawal of idelalisib and duvelisib indications (2022)

• recategorisedUntreated and relapsed: Second-generation covalent BTK inhibitors (acalabrutinib, zanubrutinib) preferred over ibrutinib after ALPINE and ELEVATE-RR head-to-head data.ibrutinib preferred → acalabrutinib or zanubrutinib preferred; ibrutinib other recommended
• addedRelapsed after covalent BTK inhibitor and venetoclax: Pirtobrutinib (non-covalent BTK inhibitor) for double-exposed disease.
• removedRelapsed: Idelalisib and duvelisib removed from routine use after their US indications were withdrawn or restricted.

Anchored to: FDA accelerated approval of lisocabtagene maraleucel for CLL after BTK and BCL-2 inhibitors, March 2024 (TRANSCEND CLL 004)

• addedRelapsed after covalent BTK inhibitor and venetoclax: CD19 CAR-T (lisocabtagene) as an option for double-exposed disease.