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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.
A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses.
Chronic lymphocytic leukaemia is a slow accumulation of mature B cells in blood, marrow, and lymph nodes, diagnosed at a median age of 70 and often found incidentally. Prognosis is set at diagnosis by IGHV mutational status, TP53 status (del(17p) or mutation), and karyotype, and by the CLL-IPI. Around a third of patients never need treatment; the rest are watched until symptoms, cytopenias, or bulky or rapidly progressive disease meet iwCLL criteria.
Treatment abandoned chemotherapy within a decade. Continuous BTK inhibitors (ibrutinib 2014, then the better-tolerated acalabrutinib and zanubrutinib) and the BCL-2 inhibitor venetoclax replaced FCR and BR after RESONATE, ELEVATE-TN, SEQUOIA, CLL13, and CLL14. Two strategies now compete in first line: indefinite BTK inhibition, or fixed-duration therapy for 12-15 months with venetoclax-obinutuzumab (CLL14) or a BTK inhibitor plus venetoclax (acalabrutinib-venetoclax, the first all-oral fixed-duration regimen approved in the US in February 2026). Undetectable MRD at the end of fixed-duration therapy predicts years of treatment-free remission. Patients with del(17p)/TP53 aberration receive continuous BTK inhibition or venetoclax-based therapy and are excluded from chemoimmunotherapy entirely.
| Setting | Approach | Guideline |
|---|---|---|
| Frontline | BTK inhibitor continuous or venetoclax-based fixed duration. | not mapped |
| Relapsed | Alternate class; pirtobrutinib; CAR-T. | not mapped |
| Early stage, asymptomatic (Rai 0-II, Binet A-B) | Watch and wait with periodic counts and examination; early treatment with ibrutinib (CLL12) delayed progression but did not improve survival and is not recommended. Vaccinations and infection prevention. | NCCN Category 1 (observation) |
| First-line, TP53-intact, fit or unfit, fixed duration | Venetoclax + obinutuzumab for 12 months (CLL14, CLL13), or acalabrutinib + venetoclax for 14 cycles (AMPLIFY; approved February 2026), or ibrutinib + venetoclax 15 months (EU; GLOW, CAPTIVATE). uMRD at end of treatment predicts durable remission; retreatment is effective. | NCCN Category 1 (venetoclax-obinutuzumab); Category 1 (acalabrutinib-venetoclax), ESMO-MCBS 4 (CLL14) |
| First-line, continuous BTK inhibition | Acalabrutinib (± obinutuzumab, ELEVATE-TN) or zanubrutinib (SEQUOIA) until progression; ibrutinib where alternatives are unavailable. Preferred for del(17p)/TP53 and for patients who cannot manage venetoclax ramp-up or TLS monitoring. | NCCN Category 1 (acalabrutinib, zanubrutinib preferred) |
| First-line, del(17p) or TP53 mutation | Continuous second-generation BTK inhibitor (zanubrutinib: 5-year PFS 72%; acalabrutinib) or venetoclax-obinutuzumab; never chemoimmunotherapy; consider clinical trial and early referral for transplant/CAR-T planning if young. | NCCN Category 1 |
| First-line, chemoimmunotherapy (limited role) | FCR only for young, fit, IGHV-mutated, TP53-intact patients who decline targeted therapy or lack access; BR in older patients likewise. Outperformed by targeted therapy in CLL13, ELEVATE-TN, SEQUOIA, AMPLIFY. | NCCN Category 2A (select patients) |
| Relapse after fixed-duration venetoclax | Retreat with venetoclax-based therapy if remission lasted >2-3 years, or switch to a BTK inhibitor (acalabrutinib, zanubrutinib); pirtobrutinib if prior covalent BTKi as well. | NCCN Category 2A |