Mantle cell lymphoma
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.
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with covalent BTK inhibitors (ibrutinib 2013, acalabrutinib 2017, zanubrutinib 2019; ibrutinib's US MCL approval was withdrawn in 2023 after SHINE), then brexucabtagene autoleucel (ZUMA-2, 2020), the non-covalent BTKi pirtobrutinib (2023), or the BCL2 inhibitor sonrotoclax (2026);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.
State of the art today
- 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.
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.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
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).
Bendamustine-rituximab + acalabrutinib (ECHO, approved 2025) or BR alone with rituximab maintenance; R-CHOP alternative.
Covalent BTK inhibitor (acalabrutinib, zanubrutinib; ibrutinib ex-US) ± venetoclax (SYMPATICO).
Brexucabtagene or lisocabtagene CAR-T; pirtobrutinib; sonrotoclax (2026); allogeneic HSCT in selected patients; bispecific trials.
Subtypes & biomarkers
top- Classical nodal MCL (SOX11+)
- Leukaemic non-nodal MCL (indolent)
- Blastoid / pleomorphic variant
- TP53-mutant MCL
- In situ mantle cell neoplasia
- 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)
Target prevalence in this cancer
- 1992Cyclin D1 and t(11;14) define MCL
Mantle cell lymphoma recognised as a distinct entity (REAL classification 1994).
- 2008MIPI prognostic index
- 2013Ibrutinib: first BTK inhibitor approved
68% response in relapsed MCL; the first indication for any BTK inhibitor.
- 2017Acalabrutinib approved (ACE-LY-004)
- 2019Zanubrutinib approved
- 2020Brexucabtagene autoleucel (ZUMA-2)
First CAR-T for MCL: 93% response after BTKi failure.
- 2023Pirtobrutinib approved; ibrutinib US MCL indication withdrawn
- 2024TRIANGLE and ECHO
Ibrutinib replaces transplant in fit patients; acalabrutinib + BR improves PFS first line in older patients.
- 2026Sonrotoclax approved for relapsed MCL
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.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research InstituteColumbus, OH, USNCI comprehensivevia Ibrutinib, Acalabrutinib
- via Allogeneic stem cell transplantation
- HOVONRotterdam, NLvia Venetoclax
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Allogeneic stem cell transplantation
- via Glofitamab
- Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CAvia Allogeneic stem cell transplantation
- LYSA – The Lymphoma Study AssociationPierre-Bénite (Lyon), FRvia Glofitamab
- via Allogeneic stem cell transplantation
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensivevia Allogeneic stem cell transplantation
- Walter and Eliza Hall Institute of Medical ResearchMelbourne, AUvia Venetoclax
Questions to ask
topQuestions to ask your oncologist about Mantle cell lymphoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example t/ cyclin D1 IHC, SOX11, MIPI and MIPI-c, Ki-67, TP53 mutation / del), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Classical nodal MCL, Leukaemic non-nodal MCL, Blastoid / pleomorphic variant.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
First line, fit (<65-70)
- For my situation (first line, fit (<65-70)), which of the standard options do you recommend and why?Why: Guideline options include: 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).
- Am I a candidate for Rituximab, Ibrutinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
First line, older or unfit
- For my situation (first line, older or unfit), which of the standard options do you recommend and why?Why: Guideline options include: Bendamustine-rituximab + acalabrutinib (ECHO, approved 2025) or BR alone with rituximab maintenance; R-CHOP alternative.
- Am I a candidate for Bendamustine, Rituximab, Acalabrutinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Relapsed, BTKi-naive
- For my situation (relapsed, btki-naive), which of the standard options do you recommend and why?Why: Guideline options include: Covalent BTK inhibitor (acalabrutinib, zanubrutinib; ibrutinib ex-US) ± venetoclax (SYMPATICO).
- Am I a candidate for Acalabrutinib, Zanubrutinib, Ibrutinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Relapsed after BTKi
- For my situation (relapsed after btki), which of the standard options do you recommend and why?Why: Guideline options include: Brexucabtagene or lisocabtagene CAR-T; pirtobrutinib; sonrotoclax (2026); allogeneic HSCT in selected patients; bispecific trials.
- Am I a candidate for Brexucabtagene autoleucel, Lisocabtagene maraleucel, Pirtobrutinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Sonrotoclax, Glofitamab, Pirtobrutinib, Venetoclax?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “TP53-mutant and blastoid MCL fail chemo-immunotherapy; need CAR-T or bispecific-based first-line trials”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “MRD-guided treatment duration”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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