Mantle Cell Lymphoma (MCL)

★★ Embedded Visual Previews

These embedded previews are shown below for quick viewing; downloadable SVG, PDF and editable Excalidraw files are available in the Visual MDT Tools panel above.

★ UK Access Key & Evidence vs Access Principle

★★ UK Access / Commissioning Snapshot

This snapshot summarises the principal NICE / NHS England access positions used as a reference for this evidence guide. Implementation may differ in Scotland (SMC), Wales (AWMSG), and Northern Ireland (HSCNI); local formulary positions should be checked. Access positions change; verify at the time of prescribing or referral.

1 Scope and Purpose

This guide addresses the diagnosis, risk stratification, and management of adults (≥18 years) with mantle cell lymphoma — including classical, blastoid, pleomorphic, and leukaemic non-nodal variants, and in situ mantle cell neoplasia (ISMCN) — within UK NHS practice.

Intended users

UK consultant haematologists, registrars and SHOs, CNS teams, haemato-oncology pharmacists, MDT coordinators. Not for direct use by patients. Not a prescribing protocol.

Out of scope

• Paediatric and adolescent MCL (extremely rare).
• Detailed pharmacology — refer to BNF and SmPC.
• Allogeneic transplant donor selection — refer to BSBMTCT guidance.

2 Methodology and Evidence Sources

• Tier 1 — UK regulatory and society: NICE TAs (TA502, TA1081, TA677), NHS England Clinical Commissioning Policies, BSH MCL Guideline — Eyre TA et al, BJH 2024;204(1):108–126 (superseding McKay et al 2018).
• Tier 2 — International societies: ESMO Clinical Practice Guidelines (Dreyling et al), EHA, NCCN.
• Tier 3 — Key RCTs: TRIANGLE, SHINE, LYMA, MCL Younger, Nordic MCL2/MCL3, VR-CAP, SYMPATICO, ECHO, ZUMA-2, TRANSCEND, BRUIN.
• Tier 4 — Emerging conference data: ASH/EHA 2023–2025, flagged [EMERGING].

Evidence grading (GRADE-adapted)

Recommendation strength: Strong (benefits clearly outweigh harms) · Conditional (greater uncertainty, shared decision-making) · Good practice statement (GPS).

3 Disease Overview

MCL is a mature B-cell NHL defined by t(11;14)(q13;q32) IGH-CCND1 translocation and cyclin D1 overexpression. SOX11 expression is characteristic of classical and aggressive MCL.

Epidemiology

• 5–7% of adult NHL in the UK.
• Median age 65–70 years; M:F approximately 3:1.
• 70–80% present at Ann Arbor stage III–IV.

Biological variants

4 Diagnosis and Pathology Requirements

Immunohistochemistry and flow cytometry

Pathology reporting minimum dataset

• Morphological variant: classical, blastoid, pleomorphic, leukaemic non-nodal.
• Ki-67 proliferation index as percentage.
• Cyclin D1 and SOX11 status.
• TP53 IHC pattern and molecular (NGS) mutation result.
• FISH t(11;14) confirmation where cyclin D1 IHC negative / equivocal.
• Bone marrow / peripheral blood involvement where assessed.
• Differential diagnosis comment where relevant.

Molecular and cytogenetic testing

• FISH for t(11;14)(q13;q32) IGH-CCND1 — mandatory if cyclin D1 IHC equivocal or negative.
• TP53 mutation analysis by NGS in every patient.
• TP53 IHC as a screening surrogate.
• Conventional karyotype where feasible — complex karyotype (≥3 aberrations) adverse.
• Broader NGS lymphoma panel (ATM, CDKN2A, NOTCH1/2, NSD2, KMT2D) where locally available.

Baseline clinical work-up and imaging

• FBC, U&E, LFT, LDH, urate, calcium, magnesium, phosphate, β2-microglobulin, immunoglobulins.
• HBsAg, anti-HBc, HCV antibody, HIV serology.
• ECG and echocardiogram if anthracycline or BTKi planned.
• Contrast-enhanced CT neck/chest/abdomen/pelvis; 18F-FDG PET-CT at baseline.
• Bone marrow aspirate and trephine with flow cytometry and IHC for cyclin D1.
• GI endoscopy with biopsy if clinically indicated.
• MRI brain and CSF flow cytometry if blastoid, high MIPI, or neurological symptoms.

5 Staging and Risk Stratification

Lugano-modified Ann Arbor staging. Most MCL presents at stage III or IV.

MIPI and MIPI-c

MIPI-c incorporates Ki-67 ≥30% as adverse; improved discrimination for high-risk patients (Hoster et al, JCO 2016).

TP53 status

TP53 mutation is the single most powerful adverse molecular biomarker. Eskelund et al (Blood 2017;130(17):1903–1910, DOI 10.1182/blood-2017-04-779736) reported median overall survival of 1.8 years in TP53-mutated cases from Nordic MCL2/MCL3 versus 12.7 years in TP53-unmutated patients, despite intensive cytarabine-containing induction and ASCT consolidation.

MDT risk category assignment

At first treatment decision, assign a documented MDT risk category:

• Standard-risk MCL — symptomatic, no TP53 mutation, non-blastoid, Ki-67 < 30%. Standard first-line pathway.
• Indolent / non-nodal MCL — asymptomatic, low Ki-67, SOX11−, IGHV mutated, leukaemic non-nodal. Watch and wait.
• High-risk MCL — high MIPI-c, Ki-67 ≥ 30%, no TP53 mutation. Consider TRIANGLE-anchored BTKi-integrated approaches where accessible; earlier CAR-T pathway.
• TP53-aberrant MCL — TP53 mutation by NGS or strong/absent TP53 IHC pattern. Prioritise trials, BTKi-based approaches, early cellular therapy planning.
• Blastoid / pleomorphic MCL — aggressive variant. High-risk pathway, consider CNS prophylaxis, early CAR-T referral.

6 First-Line Management

This section presents first-line management as a stepwise MDT algorithm. For each fitness group, options are separated into four practical categories: (A) current UK standard / routine, (B) evolving evidence-standard / access-dependent, (C) high-risk biology / selected alternative, and (D) historical / not routine. Evidence-supported does not equal NHS-commissioned — access route must be documented for any non-routine option.

6.0 Treatment Decision at Diagnosis — MDT Algorithm

Step 1 — Is this indolent / non-nodal MCL suitable for observation?

• Asymptomatic; low tumour burden; non-bulky.
• Low Ki-67; non-blastoid / non-pleomorphic.
• SOX11 negative and IGHV mutated leukaemic non-nodal phenotype where available.

Decision: watch and wait, not immediate treatment.

Step 2 — Is the patient fit for intensive / cytarabine-based treatment?

• ECOG performance status and frailty (Clinical Frailty Scale).
• Renal function (eGFR / creatinine clearance) and cardiac fitness.
• Transplant fitness and end-organ reserve.
• Comorbidity burden and patient preference.

Step 3 — Is there high-risk biology?

• TP53 mutation or TP53-aberrant pattern by IHC.
• Blastoid or pleomorphic morphology.
• High Ki-67 proliferation index.
• High MIPI-c.
• Complex karyotype (≥ 3 cytogenetic aberrations).

Decision: do not assume ASCT will overcome adverse biology. Prioritise clinical trial, BTKi-based approach where accessible, and prospective CAR-T pathway planning.

Step 4 — Check access

• NICE Technology Appraisal status.
• NHS England / local commissioning position.
• Local formulary approval.
• Compassionate / manufacturer-supported route availability.
• Individual Funding Request / exceptional funding route.
• Clinical trial availability.
• SmPC and patient-specific toxicity, interaction, and renal/hepatic considerations.

6.1 Observation Pathway

• Who to observe: asymptomatic patients with non-blastoid, low Ki-67, non-bulky MCL — particularly leukaemic non-nodal phenotype.
• What to monitor: clinical assessment, FBC, U&E, LFT, LDH; imaging only on clinical suspicion.
• When to treat: development of MCL treatment triggers — B-symptoms, progressive cytopenias attributable to marrow or splenic disease, symptomatic or bulky nodal disease, threatened organ function, rapidly progressive disease, symptomatic splenomegaly, gastrointestinal complications, or unequivocal clinical or radiological progression.
• Median time to treatment with watch-and-wait may exceed 2–4 years in selected patients.

6.2 Fit / Intensive / Transplant-Eligible Pathway

Defined pragmatically as patients fit for cytarabine-based induction and, where applicable, autologous stem-cell transplant. The four categories below should be considered in order at MDT.

6.2.A Current UK standard / routine pathway

• Cytarabine-containing immunochemotherapy (e.g. R-CHOP/R-DHAP-style induction) in fit patients.
• ASCT consolidation in selected eligible patients where BTKi integration is not accessible.
• Rituximab maintenance after ASCT (LYMA pattern, Le Gouill et al, NEJM 2017;377:1250–1260, PMID 28953447).

Position: established pathway. Remains relevant where BTKi-integrated induction is not accessible.

6.2.B Evolving evidence-standard / access-dependent pathway (TRIANGLE)

Dreyling et al, The Lancet 2024, PMID 38705160. 870 patients ≤65 randomised. Three-year failure-free survival 88% (arm A+I) vs 72% (arm A); HR 0.52; p = 0.0008. The ibrutinib-without-ASCT arm (I) was not inferior to the ibrutinib-plus-ASCT arm (A+I), with less toxicity. No demonstrated superiority of the ASCT-containing ibrutinib arm over ibrutinib without ASCT in available analysis.

Position: practice-changing evidence benchmark; not uniformly commissioned as routine UK first-line; consider where legitimate access route exists.

6.2.C High-risk biology / TP53-aberrant pathway

• TP53-mutated MCL has poor outcomes with intensive chemoimmunotherapy and ASCT (Eskelund et al, Blood 2017;130(17):1903–1910, DOI 10.1182/blood-2017-04-779736).
• ASCT should not be relied upon as the primary risk-overcoming strategy.
• Prioritise clinical trial enrolment.
• Consider BTKi-based strategies where accessible (commissioned, compassionate, manufacturer-supported, IFR, or trial).
• Map the CAR-T pathway early — refer to a JACIE-accredited CAR-T centre for forward planning.
• Consider CNS assessment / prophylaxis only where risk features and local policy support it (individualised MDT decision).

6.2.D Historical / not routine

• R-CHOP alone in fit younger patients — historically important comparator; not preferred routine pathway.
• CHOP-like therapy without cytarabine intensification — superseded by cytarabine-containing pathways.
• Automatic ASCT for every fit patient without considering TRIANGLE biology and access — no longer the default.

Position: historically important comparator or fallback only; not preferred as routine decision pathway in modern MDT practice.

6.2 First-Line Fit Pathway — Summary Table

6.3 Older / Less Fit / Non-Intensive Pathway

Defined as patients unsuitable for cytarabine-containing induction or ASCT. Functional and biological assessment outweighs chronological age.

6.3.A Current UK standard / routine pathway

• Bendamustine-rituximab (BR) — remains the practical standard for many older or less fit patients (StiL trial, Rummel et al).
• Rituximab maintenance after response where appropriate and tolerated.
• R-CHOP — only where BR is contraindicated; vigilance for anthracycline cardiotoxicity.

6.3.B Evolving evidence-standard / access-dependent pathway (ECHO / acalabrutinib + BR)

Wang ML et al, Journal of Clinical Oncology 2025;43:2276–2284. PMID 40311141. DOI 10.1200/JCO-25-00690. Phase III: 598 patients ≥65 with previously untreated MCL randomised to acalabrutinib + BR vs placebo + BR. Median follow-up 49.8 months. Median PFS 66.4 vs 49.6 months (HR 0.73; 95% CI 0.57–0.94; p = 0.016). ORR 91.0% (CR 66.6%) vs 88.0% (CR 53.5%). Overall survival was not significantly different. FDA approval was granted in January 2025 and European Commission approval on 6 May 2025 (following CHMP positive opinion), both for adults with previously untreated MCL who are ineligible for autologous HSCT.

Safety nuance (FDA prescribing information): serious adverse reactions were reported in approximately 69% of patients receiving acalabrutinib + BR, with fatal adverse reactions in approximately 12%. Common adverse reactions (≥15%) included rash, COVID-19, fatigue, diarrhoea, pneumonia, headache, upper respiratory infection, pyrexia, cough, vomiting, constipation, haemorrhage, oedema, second primary malignancy, dizziness, arthralgia, and dyspnoea. Although toxicity was considered manageable in the trial context, serious and fatal adverse reactions were reported; UK adoption should therefore depend on NICE appraisal, patient fitness, infection risk, comorbidity, and local governance.

• NICE appraisal GID-TA11091 (ID6155) — in development for acalabrutinib with bendamustine and rituximab for untreated MCL. Expected publication 4 June 2026 (may be rescheduled).
• Position: practice-informing phase III evidence with FDA / EU approval, but not adopted as routine UK standard until NICE final guidance and local commissioning are in place.
• Other BTKi-BR approaches should be discussed cautiously and not assumed standard.

6.3.C Selected alternatives / frailty pathway

• R-CHOP where BR is contraindicated.
• Palliative / attenuated approaches in frail patients.
• Single-agent or low-intensity approaches only in selected frail or palliative contexts.
• Integrate clinical nurse specialist input, pharmacy review, infection prevention, transfusion support, and specialist palliative care where appropriate, with clear treatment-escalation boundaries.

6.3.D Historical / not routine

• Routine frontline ibrutinib + BR (SHINE, Wang et al, NEJM 2022;386:2482–2494, PMID 35657079) is not adopted as UK standard. PFS benefit (6.7 vs 4.4 years) without OS advantage; excess atrial fibrillation, bleeding, and pneumonia.
• VR-CAP (LYM-3002, Robak et al, NEJM 2015) — rarely used in UK and not generally NICE-funded for first-line MCL.
• R-squared (rituximab + lenalidomide) — should not be presented as routine UK first-line unless a live funding route exists.

6.3 First-Line Older / Less Fit Pathway — Summary Table

6.4 First-Line Summary by Clinical Group

6.5 MDT Documentation Checklist (First-Line)

• Diagnosis and morphological variant confirmed.
• Ki-67 proliferation index recorded as percentage.
• TP53 mutation status by NGS, with TP53 IHC pattern.
• SOX11 and IGHV status if indolent phenotype suspected.
• MIPI and MIPI-c calculated and recorded.
• Fitness / frailty assessment (ECOG, Clinical Frailty Scale).
• Renal function (eGFR) and cardiac assessment.
• Intended pathway category: routine / evolving access-dependent / selected alternative / not routine.
• Funding / access route identified (NICE-commissioned, compassionate, manufacturer-supported, IFR, EAMS, clinical trial, locally approved exceptional pathway).
• Evidence basis identified.
• Alternatives discussed.
• Toxicity, drug interaction, and infection risk reviewed.
• Patient preference and informed consent documented.
• CAR-T centre discussion documented where high-risk or relapse planning is relevant.

6.6 CNS Prophylaxis

Evidence supporting CNS prophylaxis in MCL is limited and largely extrapolated from aggressive B-cell lymphoma practice. Routine CNS prophylaxis is not recommended for all patients. Decisions should be individualised and documented at MDT, balancing blastoid / pleomorphic morphology, high MIPI with high Ki-67, TP53 abnormality, CNS symptoms, renal function, and fitness for high-dose methotrexate.

7 Relapsed and Refractory MCL

7.1 Principles at relapse

• Re-biopsy dominant lesion where feasible — confirm relapse, exclude transformation, reassess TP53 and Ki-67.
• Re-stage with CT and PET-CT; CSF analysis if blastoid relapse or neurological features.
• Document time from prior therapy, prior agents, response duration, organ function.
• Early discussion with a JACIE CAR-T centre at first relapse for fit patients.

7.2 Covalent BTK inhibitors

In the UK, two covalent BTKi are NICE-recommended for adults with R/R MCL who have had one previous line of treatment only:

• Ibrutinib (NICE TA502): published 31 January 2018, last reviewed 8 July 2021. Subject to commercial access agreement with NHS England.
• Zanubrutinib (NICE TA1081): published 10 July 2025. Subject to simple discount patient access scheme. NICE directs use of the least-expensive option of zanubrutinib or ibrutinib, having discussed advantages and disadvantages with the patient. Funded in England within 30 days of final publication.
• Acalabrutinib: not currently NICE-recommended in MCL. Access in MCL should be verified locally. [VERIFY]

Practical UK choice between ibrutinib and zanubrutinib: TA1081 least-expensive-option directive, comorbidity, cardiovascular and bleeding risk, drug interactions, prior cardiac history, anticoagulation, and local formulary.

7.3 BTKi combination — ibrutinib + venetoclax (SYMPATICO)

Wang et al, Lancet Oncology 2025;26(2):200–213, PMID 39914418. 267 patients R/R MCL after 1–5 prior lines. Median PFS 31.9 vs 22.1 months (HR 0.65; p = 0.0052). Not routinely NICE-funded for MCL; UK access may be limited to clinical trials or individual funding. [VERIFY UK access]

7.4 Non-covalent BTKi — pirtobrutinib

Pirtobrutinib has clinically important activity post-covalent BTKi (BRUIN, BRUIN MCL-321). Routine UK NHS access should not be assumed. As of May 2026, NICE appraisal ID3975 is reported as suspended pending company evidence submission; a separate appraisal ID6493 (BTKi-untreated R/R MCL) is in development. UK access may depend on NICE publication, local formulary, compassionate, EAMS, trial, or IFR routes. [VERIFY current NICE / NHS access]

7.5 CAR-T cell therapy

Brexucabtagene autoleucel (KTE-X19)

ZUMA-2 (Wang et al, NEJM 2020;382(14):1331–1342): ORR 93%, CR 67%; three-year follow-up (PMID 35658525) confirms durable responses. NICE TA677 recommends brexucabtagene autoleucel within the Cancer Drugs Fund for adults with R/R MCL post-BTK inhibitor, subject to managed access agreement.

Important: a NICE review of TA677 (for use after two or more prior systemic treatments) is in development. CAR-T access is sensitive to managed access reviews and commissioning updates. Before referral or publication, confirm the current NHS England / NICE position. [VERIFY TA677 status]

Lisocabtagene maraleucel

TRANSCEND NHL 001 and MCL cohort report clinically meaningful activity with a potentially differentiated tolerability profile. UK access status to verify at referral. [VERIFY]

7.6 Other options

• Lenalidomide (± rituximab) in BTKi-exposed, CAR-T-ineligible patients.
• Bendamustine-rituximab if not used in first line.
• Bortezomib in selected patients.
• Allogeneic SCT for fit patients with chemosensitive disease — especially post-CAR-T or selected younger TP53-mutated patients in remission.
• Clinical trial enrolment offered whenever available.

7.7 Sequencing principles

• Preserve BTKi for relapse where possible if not used in first line.
• CAR-T eligibility window is finite — refer early, do not delay through multiple sequential lines.
• Allogeneic transplant remains an option for selected younger patients, especially post-CAR-T failure or selected TP53-mutated patients in good response.

8 UK Commissioning Status Summary

This table separates evidence position from current UK NICE / NHS England commissioning. Evidence-supported does not equal NHS-commissioned.

9 Supportive Care

Infection prophylaxis and vaccination

• Co-trimoxazole PJP prophylaxis during/after R-CHOP/R-DHAP, BR, BTKi, and CAR-T per local policy.
• Antiviral prophylaxis (aciclovir / valaciclovir) during BTKi and CAR-T pathways.
• Antifungal prophylaxis per local risk assessment.
• HBV screen and antiviral prophylaxis in HBsAg+ or anti-HBc+ patients receiving rituximab.
• Annual inactivated influenza, PCV13 + PPSV23, SARS-CoV-2 per UK schedule; avoid live vaccines during active immunosuppression.

Regimen-specific supportive care

10 Surveillance

No high-quality evidence supports imaging surveillance over symptom-driven assessment in asymptomatic remission. Routine PET-CT surveillance is not recommended.

• Clinical review every 3 months for the first 2 years, then every 6 months until 5 years, then annually.
• FBC, U&E, LFT, LDH at each visit.
• Imaging guided by clinical suspicion.
• MRD monitoring in trial contexts only.

11 How to Use This Guide in MDT

Operational workflow

• Confirm diagnosis, morphological variant, and pathology minimum dataset.
• Assign MIPI and MIPI-c.
• Confirm TP53 molecular status (NGS) and TP53 IHC pattern.
• Assign an MDT risk category.
• Define treatment intent: observe / standard / high-risk / relapse / trial.
• Check current NICE / NHS England commissioning and local formulary.
• Document trial availability and CAR-T pathway discussion.
• Document the chosen access route where non-routine.

Minimum MDT dataset

• Age, ECOG, frailty.
• Stage, bulk, LDH, WCC.
• Ki-67 percentage.
• TP53 mutation status (NGS) and TP53 IHC pattern.
• Morphological variant.
• SOX11 / IGHV phenotype if indolent disease suspected.
• Previous therapy and response duration (at relapse).
• BTKi exposure (at relapse).
• CAR-T eligibility.
• Infection risk and HBV / HCV / HIV status.
• Current NICE-commissioned option(s).
• Trial availability and patient preference.

11a Patient Consent and Shared Decision-Making for Non-Routine Access

For non-routine, compassionate, manufacturer-supported, IFR-funded, or trial-associated access, patients should be counselled and the discussion documented in the MDT record and clinic letter:

• Evidence basis and maturity of the proposed approach (peer-reviewed full publication versus conference abstract versus emerging signal).
• Funding / access route and any time-limited or conditional elements of that route.
• Uncertainty (including unknowns about long-term efficacy and toxicity in the specific subgroup).
• Toxicity profile and monitoring requirements.
• Alternatives, including standard commissioned pathways and clinical trial enrolment.
• Effect on subsequent therapy options (e.g. later BTKi, CAR-T eligibility, or trial enrolment).
• Patient preference, performance status, comorbidity, and frailty.
• Documentation in the MDT outcome and the clinic letter.

11b Devolved Nations

NICE and NHS England positions are used as the principal access reference. Implementation may differ in Scotland, Wales and Northern Ireland; clinicians should check SMC, AWMSG, HSCNI and local formulary positions where relevant.

• Scotland — Scottish Medicines Consortium (SMC) recommendations and NHS Scotland commissioning.
• Wales — All Wales Medicines Strategy Group (AWMSG) and NHS Wales commissioning.
• Northern Ireland — Health and Social Care Northern Ireland (HSCNI) commissioning.

Devolved-nation status for each named therapy should be checked locally at the time of prescribing or referral.

12 Audit Standards and KPIs

13 Emerging Evidence (Practice-Informing, Not Routine)

Emerging evidence is included for consultant-level awareness and may inform MDT discussion, trial referral, or access planning, but should not be used as the sole basis for routine treatment outside approved access routes.

Bispecific T-cell engagers

Glofitamab and epcoritamab — activity in heavily pre-treated MCL in early-phase studies and dedicated MCL cohorts. Not yet UK-approved in MCL. [EMERGING]

MRD-guided strategies

Trials exploring MRD-guided maintenance duration, treatment de-escalation, and pre-emptive intervention at MRD relapse are ongoing. Outside trials, MRD remains prognostic rather than predictive of intervention benefit. [EMERGING]

Combination strategies

Triplets including BTKi + anti-CD20 + venetoclax, and BTKi + lenalidomide + rituximab. Not yet standard. [EMERGING]

ASH / EHA 2024–2025 signals

Review primary ASH 2025 proceedings directly before citing in this guide. [VERIFY before citation]

14 References

Graded: A1 society/regulatory · A2 high-quality RCT/meta-analysis · B observational/secondary · C narrative/low certainty.

UK and society guidelines

1. Eyre TA, Bishton MJ, McCulloch R, O'Reilly M, Sanderson R, Menon G, Iyengar S, Lewis D, Lambert J, Linton KM, McKay P. Diagnosis and management of mantle cell lymphoma: A British Society for Haematology Guideline. British Journal of Haematology 2024;204(1):108–126. [A1]
2. McKay P, Leach M, Jackson B et al. Guideline for the management of mantle cell lymphoma. BJH 2018;182(1):46–62 (predecessor, superseded). [A1]
3. Dreyling M, Campo E, Hermine O et al. ESMO Clinical Practice Guidelines: Mantle Cell Lymphoma. Annals of Oncology (multiple editions). [A1]
4. NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas — current version. [A1]
5. NICE TA502: Ibrutinib for treating R/R MCL. Published 31 January 2018, last reviewed 8 July 2021. nice.org.uk/guidance/ta502. [A1]
6. NICE TA1081: Zanubrutinib for treating R/R MCL after 1 prior line. Published 10 July 2025. nice.org.uk/guidance/ta1081. [A1]
7. NICE TA677: Brexucabtagene autoleucel for treating R/R MCL (within CDF, post-BTKi). Review in development. nice.org.uk/guidance/ta677. [A1]
8. NICE appraisal ID3975 (Pirtobrutinib for R/R MCL) — suspended pending company evidence submission (May 2026). [A1]
9. NICE appraisal ID6493 (Pirtobrutinib for R/R MCL untreated with a BTKi) — in development. [A1]

Key trials and prognostic biomarkers

10. Hoster E, Dreyling M, Klapper W et al. A new prognostic index (MIPI) for advanced-stage mantle cell lymphoma. Blood 2008;111(2):558–565. PMID 17962512. DOI 10.1182/blood-2007-06-095331. [A2]
11. Hoster E, Rosenwald A, Berger F et al. Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma (MIPI-c). Journal of Clinical Oncology 2016. [A2]
12. Eskelund CW, Dahl C, Hansen JW et al. TP53 mutations identify younger MCL patients who do not benefit from intensive chemoimmunotherapy. Blood 2017;130(17):1903–1910. DOI 10.1182/blood-2017-04-779736. [A2]
13. Geisler CH et al. Nordic MCL2 follow-up. BJH. [A2]
14. Hermine O et al. Addition of high-dose cytarabine before ASCT (MCL Younger). Lancet. [A2]
15. Le Gouill S et al. Rituximab after ASCT in MCL (LYMA). NEJM 2017;377:1250–1260. PMID 28953447. DOI 10.1056/NEJMoa1701769. [A2]
16. Rummel MJ et al. Bendamustine plus rituximab vs CHOP-R (StiL). Lancet. [A2]
17. Robak T et al. VR-CAP for newly diagnosed MCL (LYM-3002). NEJM 2015. [A2]
18. Wang ML et al. Ibrutinib plus BR in untreated MCL (SHINE). NEJM 2022;386:2482–2494. PMID 35657079. DOI 10.1056/NEJMoa2201817. [A2]
19. Dreyling M et al. TRIANGLE — ibrutinib + immunochemotherapy ± ASCT in untreated MCL. The Lancet 2024. PMID 38705160. [A2]
20. Wang ML et al. KTE-X19 CAR T-cell therapy in R/R MCL (ZUMA-2). NEJM 2020;382(14):1331–1342. Three-year follow-up PMID 35658525. [A2]
21. Wang ML et al. Pirtobrutinib in covalent-BTKi pre-treated MCL (BRUIN / BRUIN MCL-321). [A2]
22. Wang ML et al. Ibrutinib + venetoclax in R/R MCL (SYMPATICO). Lancet Oncology 2025;26(2):200–213. PMID 39914418. [A2]
23. Wang ML et al. Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma (ECHO). Journal of Clinical Oncology 2025;43:2276–2284. PMID 40311141. DOI 10.1200/JCO-25-00690. [A2]
24. NICE appraisal GID-TA11091 (ID6155): Acalabrutinib with bendamustine and rituximab for untreated mantle cell lymphoma — in development. Expected publication 4 June 2026 (may be rescheduled). [A1]

15 How to Cite This Guide

Update the access year when citing.

APA

Mohsin, M. (2026). Mantle Cell Lymphoma — UK Practice-Oriented Evidence Guide. Mohsin Haematology Academy. https://mohsinhaemacademy.com/guidelines/mcl/

Vancouver

Mohsin M. Mantle Cell Lymphoma — UK Practice-Oriented Evidence Guide. Mohsin Haematology Academy; 2026. Available from: https://mohsinhaemacademy.com/guidelines/mcl/

BibTeX

@misc{mohsin_mcl_2026,
  author = {Mohsin, Muhammad},
  title  = {Mantle Cell Lymphoma --- UK Practice-Oriented Evidence Guide},
  year   = {2026},
  url    = {https://mohsinhaemacademy.com/guidelines/mcl/},
  note   = {Mohsin Haematology Academy. Educational decision-support resource.}
}

Citation etiquette: when citing this guide to inform a clinical discussion, please also cite the primary BSH, NICE, ESMO, NCCN, and trial sources. This guide is a synthesis, not a primary source.