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9 standard-of-care settings across 4 lines and 3 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.
| Line | All comers | Fit | Unfit / older |
|---|---|---|---|
| Advanced, first line | 1 | 1 | · |
| Second line | 3 | · | · |
| Special situations | · | · | 2 |
| Other settings | 2 | · | · |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | First-line mantle cell lymphoma in younger, fitter patients after TRIANGLE: ibrutinib in, transplant optional | TRIANGLE randomised 870 patients up to 65 who were fit for transplant to three arms: alternating R-CHOP and R-DHAP induction with autologous transplant (arm A); the same with ibrutinib added to induction and as two-year maintenance (arm A+I); or ibrutinib-containing induction and maintenance without transplant (arm I). Three-year failure-free survival was 88 per cent for arm A+I against 72 per cent for arm A (hazard ratio 0.52). Transplant was not shown to be superior to the ibrutinib-containing regimen without it: 72 per cent for arm A against 86 per cent for arm I. Adding ibrutinib to transplant increased grade 3 to 5 haematological events during maintenance and follow-up (50 per cent in arm A+I against 21 per cent in arm A) and infections (25 against 13 per cent). What changed in practice: a covalent BTK inhibitor belongs in first-line treatment of younger patients, and autologous transplant is no longer automatic. Many units now give ibrutinib-containing induction and maintenance without transplant, particularly in TP53-mutated disease where transplant has never worked well. Where transplant is used, rituximab maintenance afterwards improves survival: LyMa randomised 240 patients after transplant to three years of rituximab or observation and found four-year event-free survival of 79 against 61 per cent, with overall survival also improved. Cytarabine-containing induction (R-DHAP or the Nordic regimen) remains the backbone where an intensive approach is chosen. In England, NICE TA1193 allows exactly the TRIANGLE schedule: ibrutinib with R-CHOP alternating with R-DHAP or R-DHAOx, followed by ibrutinib alone, for untreated disease in adults for whom an autologous transplant is suitable. | TRIANGLEIbrutinibRituximabCytarabineCisplatinDexamethasoneOxaliplatinR-CHOP (lymphoma chemoimmunotherapy)Autologous stem cell transplant (high-dose therapy)Stem cell transplant in lymphoma: what it is still forMaintenance and consolidation in lymphoma: where it works and where it does notWhat the NHS in England funds for lymphoma, appraisal by appraisalMIPI (Mantle Cell Lymphoma International Prognostic Index)TRIANGLE: ibrutinib with immunochemotherapy with or without autologous transplant versus immunochemotherapy and transplant in untreated mantle cell lymphoma | NCCN B-Cell Lymphomas; ESMO; TRIANGLE, LyMa | 95 |
| Fit | First line, fit (<65-70) | Rituximab + high-dose cytarabine-based induction (e.g. R-CHOP/R-DHAP or Nordic) with ibrutinib and 2 years ibrutinib maintenance; autologous transplant no longer adds benefit when ibrutinib is used (TRIANGLE). | NCCN · Category 2A | 95 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Relapsed, BTKi-naive | Covalent BTK inhibitor (acalabrutinib, zanubrutinib; ibrutinib ex-US) ± venetoclax (SYMPATICO). | NCCN · Category 2A | 95 | |
| All comers | Relapsed after BTKi | Brexucabtagene or lisocabtagene CAR-T; pirtobrutinib; sonrotoclax (2026); allogeneic HSCT in selected patients; bispecific trials. | NCCN · Category 2A | 92 | |
| All comers | Relapsed mantle cell lymphoma that has not yet had a BTK inhibitor | A covalent BTK inhibitor is the standard next treatment and produces responses in about two thirds. Acalabrutinib and zanubrutinib are preferred over ibrutinib on cardiovascular toxicity where both are available. Adding venetoclax lengthens remission: SYMPATICO randomised 366 patients after one to five prior lines to ibrutinib with venetoclax or ibrutinib with placebo and gave median progression-free survival of 31.9 against 22.1 months (hazard ratio 0.629), with a complete response of 69.2 per cent in a separate open-label arm of treatment-naive TP53-mutated disease. Venetoclax carries a tumour lysis risk that requires a ramp-up and monitoring. Other options at this point are lenalidomide with rituximab, bortezomib-containing regimens, bendamustine with rituximab if not used before, and a clinical trial. Autologous transplant is rarely useful at relapse; allogeneic transplant is reserved for young, fit patients with chemosensitive disease. | NCCN B-Cell Lymphomas; ESMO; SYMPATICO | 95 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| Unfit / older | First line, older or unfit | Bendamustine-rituximab + acalabrutinib (ECHO, approved 2025) or BR alone with rituximab maintenance; R-CHOP alternative. | NCCN · Category 1 (BR + acalabrutinib) | 87 | |
| Unfit / older | First-line mantle cell lymphoma in older patients: the British answer and the international one | Two randomised trials, two different regimens, and a real difference between British and American practice. ENRICH, run at 66 sites in the United Kingdom and the Nordic countries, randomised 397 patients aged 60 and over to ibrutinib with rituximab or to the investigator's choice of immunochemotherapy (R-CHOP or bendamustine-rituximab), both followed by two years of rituximab maintenance, with ibrutinib continued until progression. At a median follow-up of 47.9 months the adjusted hazard ratio for progression-free survival was 0.69 in favour of ibrutinib-rituximab. The benefit was concentrated where the comparator was R-CHOP (hazard ratio 0.37) and was not demonstrated against bendamustine-rituximab (0.91). Grade 3 or worse adverse events were similar (67 against 70 per cent). This is the first randomised trial in untreated mantle cell lymphoma to show a chemotherapy-free combination beating immunochemotherapy, and it is British practice. SHINE took the other route and added ibrutinib to bendamustine-rituximab in 523 patients aged 65 and over: median progression-free survival 80.6 against 52.9 months (hazard ratio 0.75) with no overall survival difference and grade 3 or 4 adverse events in 81.5 against 77.3 per cent. So: ibrutinib-rituximab without chemotherapy for a patient in whom bendamustine is unattractive, and bendamustine-rituximab with or without a BTK inhibitor otherwise. Acalabrutinib and zanubrutinib are the second-generation covalent BTK inhibitors, with less atrial fibrillation and hypertension than ibrutinib, and are substituted in patients with cardiac risk. Acalabrutinib with bendamustine and rituximab received traditional United States approval on 16 January 2025 on the ECHO trial for untreated mantle cell lymphoma in people not eligible for an autologous transplant, and NICE TA1184 recommends the same combination in England for the same group. VR-CAP, which replaces vincristine with bortezomib, is an alternative backbone. | IbrutinibRituximabBendamustineAcalabrutinibZanubrutinibBortezomibR-CHOP (lymphoma chemoimmunotherapy)British and American lymphoma practice: where they differ, and whyMaintenance and consolidation in lymphoma: where it works and where it does notThe lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest | NCCN B-Cell Lymphomas; ESMO; ENRICH, SHINE | 95 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Mantle cell lymphoma: the three things to establish before choosing treatment | Mantle cell lymphoma is not one disease. Classical nodal disease behaves aggressively and needs treatment. Leukaemic non-nodal mantle cell lymphoma, with SOX11-negative, hypermutated immunoglobulin genes, splenomegaly and circulating cells but no lymphadenopathy, can be watched for years, and treating it early does harm without benefit. Blastoid and pleomorphic variants behave much more aggressively. Three things to establish. First, the growth pattern and Ki-67 index: above about 30 per cent signals aggressive disease. Second, TP53 mutation status, which is the single strongest adverse factor and predicts poor response to intensive chemotherapy and to autologous transplant; a TP53-mutated patient is a candidate for a novel-agent regimen or a trial rather than for intensification. Third, the MIPI score, which combines age, performance status, LDH and white cell count. Gastrointestinal involvement is near-universal at a microscopic level and colonoscopy is not required in every patient. | NCCN B-Cell Lymphomas; ESMO; BSH | 80 | |
| All comers | Mantle cell lymphoma after a BTK inhibitor has failed: brexucabtagene autoleucel and pirtobrutinib | Progression on a covalent BTK inhibitor was, until 2020, the point at which there was little left. Two treatments changed it. Brexucabtagene autoleucel, a CD19 CAR-T product, was tested in ZUMA-2 in 105 patients who had all had a BTK inhibitor: objective response 93 per cent and complete response 67 per cent in the primary efficacy analysis, 85 per cent by intention to treat, with progression-free survival of 61 per cent and overall survival of 83 per cent at twelve months. The toxicity is real: grade 3 or higher cytokine release syndrome in 15 per cent and grade 3 or higher neurological events in 31 per cent, higher than the CD19 products used in large B-cell lymphoma. Referral should happen as the BTK inhibitor starts to fail, not after the next line, because apheresis quality falls with further treatment. Pirtobrutinib, a non-covalent BTK inhibitor, works after covalent BTK inhibitor failure including in the presence of the C481S resistance mutation, and is an option for patients who are not candidates for CAR-T or who need disease control while a CAR-T product is manufactured. Lisocabtagene maraleucel is the second CAR-T option, approved in the United States on 30 May 2024 for relapsed or refractory mantle cell lymphoma after at least two prior lines including a BTK inhibitor. Other options are venetoclax-based combinations, glofitamab with pirtobrutinib in a trial, allogeneic transplant in selected younger patients, and palliative radiotherapy to a symptomatic site. This is a point at which a trial is often the best available treatment. | ZUMA-2Brexucabtagene autoleucelLisocabtagene maraleucelPirtobrutinibVenetoclaxGlofitamabCAR-T cell therapyThe CAR-T pathway in lymphoma: referral, apheresis, bridging and the waitingCytokine release syndrome and ICANS: grading and managementAllogeneic stem cell transplantationPalliative radiotherapyZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors | NCCN B-Cell Lymphomas; ESMO; ZUMA-2 | 92 |
Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.