Chronic Lymphocytic Leukemia: Treatment

Chronic Lymphocytic Leukemia: overview

This algorithm covers treatment of chronic lymphocytic leukemia once therapy is indicated, with del(17p) or TP53 status as the first branch point. In both the del(17p)/TP53 and the no del(17p) frontline branches, the chart offers the same two strategies: continuous therapy with a BTK inhibitor (a covalent BTK inhibitor is specified for del(17p)/TP53), supported by ELEVATE-TN, or fixed-duration venetoclax plus obinutuzumab, supported by CLL14. In the site's summaries, ELEVATE-TN showed that acalabrutinib-based regimens prolonged PFS over chlorambucil-obinutuzumab with less atrial fibrillation than ibrutinib, and CLL14 showed that time-limited venetoclax plus obinutuzumab prolonged PFS and produced higher MRD-negativity rates than chlorambucil-obinutuzumab.

For relapsed or refractory disease, the options are fixed-duration venetoclax plus rituximab (MURANO), which improved PFS and OS over bendamustine plus rituximab, pirtobrutinib, shown on the chart as a class switch (BRUIN), and CD19 CAR-T therapy with lisocabtagene maraleucel (TRANSCEND CLL).

Trials behind this algorithm

• ELEVATE-TN Sharman JP et al, Lancet, 2020; PMID: 32305093
• CLL14 Al-Sawaf O et al, Lancet Oncol, 2020; PMID: 32888452
• MURANO Seymour JF et al, NEJM, 2018; PMID: 29562156
• BRUIN (phase 1/2) Mato AR et al, NEJM, 2023; PMID: 37407001
• TRANSCEND CLL 004 Siddiqi T et al, Lancet, 2023; PMID: 37295445

Background reading: Chronic lymphocytic leukemia (CLL/SLL) board review notes.