# Mantle cell lymphoma

Source: https://onco.cc/cancers/mantle-cell-lymphoma/  
OnCo record `mantle-cell-lymphoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An uncommon B-cell lymphoma driven by cyclin D1 that used to behave badly in almost everyone. BTK inhibitors, CAR-T and now BCL2 drugs have changed it from chemotherapy-plus-transplant to targeted combinations.

## Summary

Mantle cell lymphoma (MCL) carries t(11;14) with cyclin D1 overexpression (SOX11-positive in classical MCL). Risk is set by MIPI, Ki-67, blastoid morphology and TP53 mutation, the last defining a group that fails chemo-immunotherapy and transplant. A leukaemic non-nodal variant behaves indolently.

Younger fit patients traditionally received cytarabine-containing induction and autologous transplant with rituximab maintenance; TRIANGLE (2024) showed adding ibrutinib to induction and maintenance is at least as good as transplant, and transplant is being abandoned. Older patients receive bendamustine-rituximab or R-CHOP; ECHO (2024) added acalabrutinib to BR first line (FDA approval 2025). Relapse is treated with covalent BTK inhibitors (ibrutinib 2013, acalabrutinib 2017, zanubrutinib 2019; ibrutinib's US MCL approval was withdrawn in 2023 after SHINE), then brexucabtagene autoleucel (ZUMA-2, 2020), the non-covalent BTKi pirtobrutinib (2023), or the BCL2 inhibitor sonrotoclax (2026); venetoclax-ibrutinib (SYMPATICO) is another option. Lisocabtagene was approved for MCL in 2024.

TP53-mutant MCL still does poorly with everything except CAR-T and bispecifics; glofitamab and CD20×CD3 agents are in phase 3.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; haematologic
- Group: haematologic
- Burden: Mantle cell lymphoma makes up about 5-7% of non-Hodgkin lymphomas; incidence ~1 per 100,000 per year, median age ~68, 3:1 male.
- Subtypes: Classical nodal MCL (SOX11+); Leukaemic non-nodal MCL (indolent); Blastoid / pleomorphic variant; TP53-mutant MCL; In situ mantle cell neoplasia
- Biomarkers: t(11;14) / cyclin D1 IHC; SOX11; MIPI and MIPI-c; Ki-67 (≥30% high risk); TP53 mutation / del(17p); Blastoid morphology; MRD (ctDNA/clonoSEQ, investigational)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/mantle-cell-lymphoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/mantle-cell-lymphoma/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/mantle-cell-lymphoma/#what-it-is [5 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/mantle-cell-lymphoma/#finding-it [7 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/mantle-cell-lymphoma/#treating-it [4 settings, 4 regimens, 4 decisions with options]
- Evidence (own page): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/mantle-cell-lymphoma/evidence/ [35 trials, 2 key papers, 9 milestones]
- The science (own page): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/mantle-cell-lymphoma/science/ [59 targets, 4 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/mantle-cell-lymphoma/where-you-are/ [1 centre]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/mantle-cell-lymphoma/#living-with-it [19 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/mantle-cell-lymphoma/coming/ [21 medicines, 35 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/mantle-cell-lymphoma/data/ [175 connected records]

## Standard of care

- 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). ([Rituximab](https://onco.cc/drugs/rituximab/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [TRIANGLE](https://onco.cc/trials/triangle/))
- First line, older or unfit: Bendamustine-rituximab + acalabrutinib (ECHO, approved 2025) or BR alone with rituximab maintenance; R-CHOP alternative. ([Bendamustine](https://onco.cc/drugs/bendamustine/), [Rituximab](https://onco.cc/drugs/rituximab/), [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/))
- Relapsed, BTKi-naive: Covalent BTK inhibitor (acalabrutinib, zanubrutinib; ibrutinib ex-US) ± venetoclax (SYMPATICO). ([Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [SYMPATICO](https://onco.cc/trials/sympatico/))
- Relapsed after BTKi: Brexucabtagene or lisocabtagene CAR-T; pirtobrutinib; sonrotoclax (2026); allogeneic HSCT in selected patients; bispecific trials. ([Brexucabtagene autoleucel](https://onco.cc/drugs/brexucabtagene-autoleucel/), [Lisocabtagene maraleucel](https://onco.cc/drugs/lisocabtagene-maraleucel/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [Sonrotoclax](https://onco.cc/drugs/sonrotoclax/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))

## State of the art

- Transplant is leaving first-line MCL: TRIANGLE made ibrutinib-containing induction and maintenance the new fit-patient standard.
- BTK inhibitors sit in first line for older patients (ECHO) and at relapse; pirtobrutinib rescues covalent-BTKi failures.
- CAR-T (ZUMA-2) gives long remissions after BTKi failure, including in TP53-mutant disease.
- BCL2 inhibition is back: sonrotoclax approved for relapsed MCL in 2026 with venetoclax combinations close behind.

## Open problems

- TP53-mutant and blastoid MCL fail chemo-immunotherapy; need CAR-T or bispecific-based first-line trials.
- MRD-guided treatment duration.
- Whether CAR-T should precede pirtobrutinib or follow it.
- Cost and access of indefinite BTK-inhibitor therapy.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Mantle_cell_lymphoma
- TRIANGLE (Lancet 2024): https://doi.org/10.1016/S0140-6736(24)00184-3
- NCCN Guidelines: B-Cell Lymphomas: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480
- NCI PDQ: adult NHL: https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant)](https://onco.cc/cancers/splenic-b-cell-lymphoma-leukaemia-prominent-nucleoli/), [Waldenström macroglobulinaemia](https://onco.cc/cancers/waldenstrom/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Autologous CAR-T manufacturing, batch by batch](https://onco.cc/technologies/car-t-manufacturing-process/), [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [ADRM1](https://onco.cc/targets/adrm1/), [B2M](https://onco.cc/targets/b2m/), [BCL-2](https://onco.cc/targets/bcl2/), [BIRC3](https://onco.cc/targets/birc3/), [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CD19](https://onco.cc/targets/cd19/), [CD20](https://onco.cc/targets/cd20/), [CD3](https://onco.cc/targets/cd3/), [CD79b](https://onco.cc/targets/cd79b/), [CDK4/6](https://onco.cc/targets/cdk4-6/), [CUL4A](https://onco.cc/targets/cul4a/), [DAZAP1](https://onco.cc/targets/dazap1/), [DDB1](https://onco.cc/targets/ddb1/), [HNRNPH1](https://onco.cc/targets/hnrnph1/), [MEF2B](https://onco.cc/targets/mef2b/), [NFKBIE](https://onco.cc/targets/nfkbie/), [Proteasome (PSMB5)](https://onco.cc/targets/proteasome/), [PSMA1](https://onco.cc/targets/psma1/), [PSMA2](https://onco.cc/targets/psma2/), [PSMA3](https://onco.cc/targets/psma3/), [PSMA4](https://onco.cc/targets/psma4/), [PSMA5](https://onco.cc/targets/psma5/), [PSMA6](https://onco.cc/targets/psma6/), [PSMA7](https://onco.cc/targets/psma7/), [PSMA8](https://onco.cc/targets/psma8/), [PSMB1](https://onco.cc/targets/psmb1/), [PSMB10](https://onco.cc/targets/psmb10/), [PSMB11](https://onco.cc/targets/psmb11/), [PSMB2](https://onco.cc/targets/psmb2/), [PSMB3](https://onco.cc/targets/psmb3/), [PSMB4](https://onco.cc/targets/psmb4/), [PSMB6](https://onco.cc/targets/psmb6/), [PSMB7](https://onco.cc/targets/psmb7/), [PSMB8](https://onco.cc/targets/psmb8/), [PSMB9](https://onco.cc/targets/psmb9/), [PSMC1](https://onco.cc/targets/psmc1/), [PSMC2](https://onco.cc/targets/psmc2/), [PSMC3](https://onco.cc/targets/psmc3/), [PSMC4](https://onco.cc/targets/psmc4/), [PSMC5](https://onco.cc/targets/psmc5/), [PSMC6](https://onco.cc/targets/psmc6/), [PSMD1](https://onco.cc/targets/psmd1/), [PSMD11](https://onco.cc/targets/psmd11/), [PSMD12](https://onco.cc/targets/psmd12/), [PSMD13](https://onco.cc/targets/psmd13/), [PSMD14](https://onco.cc/targets/psmd14/), [PSMD2](https://onco.cc/targets/psmd2/), [PSMD3](https://onco.cc/targets/psmd3/), [PSMD4](https://onco.cc/targets/psmd4/), [PSMD6](https://onco.cc/targets/psmd6/), [PSMD7](https://onco.cc/targets/psmd7/), [PSMD8](https://onco.cc/targets/psmd8/), [RBX1](https://onco.cc/targets/rbx1/), [S1PR1](https://onco.cc/targets/s1pr1/), [SEM1](https://onco.cc/targets/sem1/), [SP140](https://onco.cc/targets/sp140/), [UBR5](https://onco.cc/targets/ubr5/), [ZEB1](https://onco.cc/targets/zeb1/)
- drugs: [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Bendamustine](https://onco.cc/drugs/bendamustine/), [BGB-16673](https://onco.cc/drugs/bgb-16673/), [Brexucabtagene autoleucel](https://onco.cc/drugs/brexucabtagene-autoleucel/), [clonoSEQ](https://onco.cc/drugs/clonoseq/), [CTX112](https://onco.cc/drugs/ctx112/), [Glofitamab](https://onco.cc/drugs/glofitamab/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [ICP-248](https://onco.cc/drugs/icp-248/), [Lisocabtagene maraleucel](https://onco.cc/drugs/lisocabtagene-maraleucel/), [Nemtabrutinib](https://onco.cc/drugs/nemtabrutinib/), [Orelabrutinib](https://onco.cc/drugs/orelabrutinib/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [Plerixafor](https://onco.cc/drugs/plerixafor/), [Rituximab](https://onco.cc/drugs/rituximab/), [Rocbrutinib](https://onco.cc/drugs/rocbrutinib/), [Sonrotoclax](https://onco.cc/drugs/sonrotoclax/), [Temsirolimus](https://onco.cc/drugs/temsirolimus/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [Zamtocabtagene autoleucel](https://onco.cc/drugs/zamtocabtagene-autoleucel/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/)
- companies: [AbbVie (incl. ImmunoGen, Capstan)](https://onco.cc/companies/abbvie/), [AstraZeneca](https://onco.cc/companies/astrazeneca/), [BeOne Medicines (formerly BeiGene)](https://onco.cc/companies/beone/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Eli Lilly (incl. Loxo)](https://onco.cc/companies/eli-lilly/), [Gilead Sciences (incl. Kite)](https://onco.cc/companies/gilead/), [Lupeng Pharmaceuticals](https://onco.cc/companies/lupeng-pharmaceuticals/), [Miltenyi Biomedicine](https://onco.cc/companies/miltenyi-biomedicine/), [SymBio Pharmaceuticals](https://onco.cc/companies/symbio-pharmaceuticals/), [Vironexis Biotherapeutics](https://onco.cc/companies/vironexis-biotherapeutics/)
- pathways: [B-cell receptor / BTK signalling (to NF-κB)](https://onco.cc/pathways/bcr-signalling/), [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [Ubiquitin-proteasome system & protein homeostasis](https://onco.cc/pathways/ubiquitin-proteasome-system/)
- terms: [BTK C481S, PLCG2 and BCL2 G101V resistance mutations](https://onco.cc/terms/btki-bcl2i-resistance-mutations/), [del(17p) / TP53 aberration in CLL](https://onco.cc/terms/del17p-tp53/), [Lugano classification / Ann Arbor staging](https://onco.cc/terms/lugano-classification/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [MIPI (Mantle Cell Lymphoma International Prognostic Index)](https://onco.cc/terms/mipi/), [t(11;14), cyclin D1 and SOX11](https://onco.cc/terms/cyclin-d1-t11-14/)
- trials: [A Dose-Escalation and Expansion Study of Tacabrutideg (BGB-16673) in Participants With B-Cell Malignancies](https://onco.cc/trials/nct05006716/), [A Global Phase 3 Study of Orelabrutinib+BR Vs.BR in Pts with TN MCL](https://onco.cc/trials/nct06363994/), [A Long-term Extension Study of PCI-32765 (Ibrutinib)](https://onco.cc/trials/nct01804686/), [A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies](https://onco.cc/trials/nct05643742/), [A Study of Acalabrutinib Plus Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma](https://onco.cc/trials/nct05951959/), [A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies](https://onco.cc/trials/nct06564038/), [A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL](https://onco.cc/trials/nct02972840/), [A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)](https://onco.cc/trials/nct03162536/), [A Study of Rocbrutinib in Combination With Lacutoclax in Patients With B-Cell Malignancies](https://onco.cc/trials/nct07609862/), [A Study of Rocbrutinib in Participants With Relapse or Refractory Mantle Cell Lymphoma](https://onco.cc/trials/nct05716087/), [A Study of Rocbrutinib Versus Investigator's Choice of BTK Inhibitors in Patients With Relapsed or Refractory Mantle Cell Lymphoma](https://onco.cc/trials/nct07377578/), [A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-](https://onco.cc/trials/nct05458297/), [A Study to Evaluate Acalabrutinib, in Combination With the R-CHOP Standard of Care, for Previously Untreated Mantle Cell Lymphoma in Spain](https://onco.cc/trials/nct07029737/), [A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma](https://onco.cc/trials/nct06084936/), [A Study to Evaluate the Efficacy and Safety of ICP-248 in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (APEX-06)](https://onco.cc/trials/nct07082686/), [A Study to Investigate the Efficacy and Safety of Sonrotoclax Plus Zanubrutinib Compared With Placebo Plus Zanubrutinib in Adults With Relapsed/Refrac](https://onco.cc/trials/nct06742996/), [A Study to Investigate the Efficacy of Zanubrutinib Plus Rituximab Compared With Bendamustine Plus Rituximab in Adults With Previously Untreated Mantl](https://onco.cc/trials/nct04002297/), [A Study to Investigate the Safety of Novel Dose Ramp-up Schedule(s) When Initiating Sonrotoclax in Participants Treated for Blood Cancers.](https://onco.cc/trials/nct06697184/), [An Open-label, Phase 2 Study of ACP-196 (Acalabrutinib) in Subjects With Mantle Cell Lymphoma](https://onco.cc/trials/nct02213926/), [CD19-targeted CAR T Cells for Relapsed and Refractory (R/R) Mantle Cell Lymphoma](https://onco.cc/trials/nct04718883/), [DALY II USA/ MB-CART2019.1 for DLBCL](https://onco.cc/trials/nct04792489/), [Gene Therapy for CD19-Positive Hematologic Malignancies (SENTRY-CD19)](https://onco.cc/trials/nct06533579/), [Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma](https://onco.cc/trials/nct06252675/), [Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD](https://onco.cc/trials/nct00186628/), [Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malign](https://onco.cc/trials/nct03932331/), [Study of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma](https://onco.cc/trials/nct05471843/), [Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)](https://onco.cc/trials/nct04662255/), [Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom](https://onco.cc/trials/nct02952508/), [Study of KTE-X19 in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic L](https://onco.cc/trials/nct06253663/), [Study to Assess the Efficacy and Safety of Ublituximab + Umbralisib With or Without Bendamustine and Umbralisib Alone in Patients With Previously Treated Non-Hodgkins Lymphoma](https://onco.cc/trials/nct02793583/), [SYMPATICO](https://onco.cc/trials/sympatico/), [Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader](https://onco.cc/trials/nct05294731/), [TRIANGLE](https://onco.cc/trials/triangle/), [Zevalin and Velcade in Relapsed/Refractory Mantle Cell Lymphoma](https://onco.cc/trials/nct01497275/), [ZUMA-2](https://onco.cc/trials/zuma-2/)
- people: [Constantine S. Tam](https://onco.cc/people/constantine-tam/), [Martin Dreyling](https://onco.cc/people/martin-dreyling/), [Michael L. Wang](https://onco.cc/people/michael-wang/), [Yuqin Song](https://onco.cc/people/yuqin-song/)
- collections: [Leukemia & Lymphoma Society (LLS)](https://onco.cc/collections/leukemia-lymphoma-society/), [Lymphoma Research Foundation (LRF)](https://onco.cc/collections/lymphoma-research-foundation/)
- key papers: [TRIANGLE: ibrutinib with immunochemotherapy with or without autologous transplant versus immunochemotherapy and transplant in untreated mantle cell lymphoma](https://onco.cc/key-papers/paper-triangle-ibrutinib-mantle-cell-lymphoma-dreyling-lancet-2024/), [ZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors](https://onco.cc/key-papers/paper-zuma-2-brexu-cel-mantle-cell-nejm-2020/)
- institutions: [Alfred Health / Monash University](https://onco.cc/institutions/alfred-health-monash/)
- biomarkers: [CD19 expression (CD19-positive)](https://onco.cc/biomarkers/cd19-expression/), [CD20 expression (CD20-positive)](https://onco.cc/biomarkers/cd20-expression/)
- journals: [Clinical lymphoma, myeloma & leukemia](https://onco.cc/journals/clinical-lymphoma-myeloma-and-leukemia/), [Current hematologic malignancy reports](https://onco.cc/journals/current-hematologic-malignancy-reports/), [Leukemia & lymphoma](https://onco.cc/journals/leukemia-and-lymphoma/)

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JSON: https://onco.cc/api/v1/entities/mantle-cell-lymphoma.json