• del(17p) / TP53 aberration in CLL: A del(17p) deletion or TP53 mutation means loss or damage of the p53 safety gene in CLL.
• R-CHOP (lymphoma chemoimmunotherapy): R-CHOP is the standard first treatment for diffuse large B-cell lymphoma: rituximab (an antibody against CD20) plus four chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, prednisone), given every three weeks for six cycles with curative intent.
• Richter transformation: When slow CLL suddenly turns into an aggressive lymphoma.
• IGHV mutational status: Whether the leukaemia's antibody gene has been 'edited' by the immune system.
• Fixed-duration vs continuous therapy: Whether a drug is taken for a set period (say 12 months) and then stopped even though it is still working, or continued indefinitely until it fails.
• MRD-negative complete remission: MRD-negative complete remission means not just no leukaemia visible under the microscope, but none detectable with tests a thousand times more sensitive.
• Lymphoma (tissue type): Cancer of lymphocytes, the white blood cells of the immune system, usually growing as masses in lymph nodes, spleen or other organs.
• B cell: The immune cells that make antibodies.
• Leukaemia (tissue type): Cancer of the blood-forming cells in the bone marrow, which flood the blood with immature or abnormal white cells and crowd out normal blood production.
• Undetectable MRD (uMRD / MRD-negative): The test for leftover cancer cells found none, down to the sensitivity of the assay (often one cell in 100,000 or a million).

Biomarker results to ask for: del(17p)/TP53, IGHV mutation status, del(11q), BTK/PLCG2 resistance mutations, MRD, IGHV mutational status (<2% deviation = unmutated), TP53 mutation and del(17p) by FISH, FISH panel: del(13q), del(11q), trisomy 12, del(17p), Complex karyotype, NOTCH1, SF3B1, BIRC3 mutations, β2-microglobulin and CLL-IPI score, MRD by flow or clonoSEQ at end of fixed-duration therapy, BTK C481S/T474I/L528W and PLCG2 mutations at BTKi progression, BCL2 G101V and other mutations at venetoclax progression, Hepatitis B serology before anti-CD20 therapy.

Scans and tests linked to this cancer: Cytogenetics and FISH, Flow cytometers, Multiparameter flow cytometry MRD, NGS-based MRD (clonoSEQ and molecular MRD), MRD / molecular residual disease testing, BH3 profiling (functional apoptosis testing).

Bring copies of scan reports, pathology and blood results, and a list of every medicine and supplement.

• 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. (Ibrutinib, IGHV mutational status)
• Frontline: BTK inhibitor continuous or venetoclax-based fixed duration. (Venetoclax)
• 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. (Venetoclax, Obinutuzumab, Acalabrutinib, CLL14, CLL13 / GAIA, AMPLIFY, BTK inhibitor + venetoclax, fixed duration)
• 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. (Acalabrutinib, Zanubrutinib, Ibrutinib, ELEVATE-TN, SEQUOIA)
• 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. (Zanubrutinib, Acalabrutinib, Venetoclax, SEQUOIA, del(17p) / TP53 aberration in CLL, Caution: chemoimmunotherapy in del(17p)/TP53 CLL)
• 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. (Rituximab, CLL13 / GAIA)
• Progression on a covalent BTK inhibitor: Venetoclax-based therapy (venetoclax-rituximab 24 months, MURANO) or pirtobrutinib (BRUIN CLL-321; traditional approval December 2025); BTK degraders (BGB-16673 vs pirtobrutinib, CaDAnCe-304) in trials. (Venetoclax, Pirtobrutinib, BGB-16673, BRUIN CLL-321, CaDAnCe-304)
• Richter transformation: Biopsy to confirm and assess clonal relationship; chemoimmunotherapy (R-CHOP) has poor results; checkpoint inhibitor + BTK inhibitor (zanubrutinib-tislelizumab, RT1), pirtobrutinib, venetoclax-based regimens, CD20×CD3 bispecifics (epcoritamab, glofitamab), CAR-T; allogeneic transplant for responders. (Richter transformation, Pirtobrutinib, Zanubrutinib, Glofitamab, Allogeneic stem cell transplantation)
• Relapsed: Alternate class; pirtobrutinib; CAR-T. (CAR-T cell therapy)
• 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. (Venetoclax, Zanubrutinib, Acalabrutinib, Pirtobrutinib)
• Double-refractory (BTKi and BCL2i): Pirtobrutinib if BTK-naive-to-noncovalent; lisocabtagene maraleucel CAR-T (TRANSCEND CLL 004; accelerated approval 2024); allogeneic transplant in fit patients; PI3K inhibitors (idelalisib, duvelisib) rarely; clinical trials of degraders, sonrotoclax, bispecifics. (Pirtobrutinib, Lisocabtagene maraleucel, TRANSCEND CLL 004, Allogeneic stem cell transplantation, Sonrotoclax)
• Supportive care throughout: Infection prophylaxis and vaccination (non-live; reduced vaccine responses), IVIG for recurrent infections with hypogammaglobulinaemia, HBV screening before anti-CD20, skin cancer surveillance (second cancers), cardio-oncology review before ibrutinib, TLS prophylaxis with venetoclax. (Tumour lysis syndrome (TLS), Cardio-oncology, Caution: ibrutinib in patients with cardiac risk)

From the standard of care recorded for this cancer; which apply depends on your stage and biomarkers. Ask which the team recommends and why.