Loading
10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Chronic lymphocytic leukaemia is treated only when it causes problems, and chemotherapy has gone. The first treatment is now either a BTK inhibitor taken indefinitely or a one-year course of venetoclax with obinutuzumab (CLL14), and the two can be combined for a fixed course.
Diagnosis needs 5 x 10^9/L clonal B cells with the typical CD5, CD19, CD23 phenotype; treatment starts only for iwCLL indications (symptoms, progressive anaemia or thrombocytopenia, bulky or fast-growing disease), because early treatment, even with ibrutinib in CLL12, has not lengthened life. Before the first treatment, every patient has FISH and sequencing for del(17p) and TP53 mutation and testing of IGHV mutational status, since these decide the regimen: TP53-aberrant disease does not respond durably to chemotherapy, and unmutated IGHV disease relapses early after it.
Two families of drugs replaced chemoimmunotherapy between 2014 and 2023. Continuous BTK inhibitors, ibrutinib and then the better-tolerated acalabrutinib (ELEVATE-TN, versus chlorambucil-obinutuzumab: median progression-free survival not reached at six years against 27.8 months) and zanubrutinib (SEQUOIA, versus bendamustine-rituximab, hazard ratio 0.42), control the disease for years but must be taken indefinitely and carry atrial fibrillation, bleeding and hypertension risks. Fixed-duration venetoclax with obinutuzumab for 12 months (CLL14, versus chlorambucil-obinutuzumab in older unfit patients: six-year progression-free survival 53.1 percent versus 21.7 percent, hazard ratio 0.40) gives most patients undetectable MRD and years off treatment; CLL13/GAIA confirmed the same in fit patients, where venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib beat fludarabine-based chemoimmunotherapy (five-year progression-free survival 69.8 and 81.3 percent against 50.7 percent).
| Setting | Approach | Guideline |
|---|---|---|
| Asymptomatic early-stage disease | Watch and wait with counts every three to twelve months; treat only on iwCLL indications. | not mapped |
| First treatment, fixed duration | Venetoclax plus obinutuzumab for 12 months (CLL14, CLL13); ibrutinib-venetoclax (GLOW, CAPTIVATE) or acalabrutinib-venetoclax with or without obinutuzumab (AMPLIFY) for fit patients. | not mapped |
| First treatment, continuous | Acalabrutinib (ELEVATE-TN) or zanubrutinib (SEQUOIA) until progression, preferred for del(17p) or TP53-mutated disease; ibrutinib where the newer agents are unavailable. | not mapped |
| Chemoimmunotherapy | Fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab only for IGHV-mutated disease without TP53 aberration where targeted drugs are unavailable; never for del(17p). | not mapped |