OnCo
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Diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive but curable lymphoma. CAR-T cures about 40% of relapsed patients, and off-the-shelf bispecifics are now approved.

Diffuse large B-cell lymphoma is the most common aggressive lymphoma, about 30% of all non-Hodgkin lymphoma, with a median age around 65. It is curable: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) cures roughly 60% of patients, more with low IPI and fewer with high-risk features (IPI 3-5, double-hit MYC/BCL2 rearrangement, activated B-cell origin, TP53 loss). Staging uses PET-CT and the Lugano classification; biology is read from cell of origin and FISH for MYC, BCL2 and BCL6, with genetic classifiers (LymphGen) and ctDNA emerging.

Frontline therapy stood still for twenty years until POLARIX (2022) showed that replacing vincristine with the CD79b ADC polatuzumab vedotin improves progression-free survival (5-year 64.9% vs 59.1%), and frontMIND (Lancet 2026) showed tafasitamab plus lenalidomide added to R-CHOP improves PFS in IPI 3-5 disease (HR 0.75); epcoritamab plus R-CHOP (EPCORE DLBCL-2) and golcadomide plus R-CHOP (GOLSEEK-1) follow. For the 30-40% who relapse, the sequence has been rebuilt around T-cell redirection: CD19 CAR-T (axi-cel, liso-cel) beats salvage chemotherapy and transplant for relapse within a year (ZUMA-7 with an overall survival benefit; TRANSFORM), while transplant remains for later chemosensitive relapse. Off-the-shelf CD20×CD3 bispecifics (glofitamab, epcoritamab, mosunetuzumab, odronextamab) give complete remissions in about 40% of heavily pretreated patients, and chemotherapy-free doublets such as mosunetuzumab-polatuzumab (SUNMO) beat salvage chemotherapy. CD19 ADC (loncastuximab), tafasitamab-lenalidomide, and the ROR1 ADC zilovertamab vedotin fill later lines.

The open questions are regulatory as much as scientific. EPCORE DLBCL-1 (2026) improved PFS but not overall survival against chemotherapy; STARGLO's survival benefit was rejected by the FDA because the trial was mostly enrolled in Asia. Nobody has compared bispecifics with CAR-T head to head. ctDNA (PhasED-seq) predicts cure better than PET and is the obvious tool for response-adapted frontline therapy. Primary refractory disease, CNS relapse, older and frail patients, and access to CAR-T outside major centres remain the hard problems.

State of the art today

  • CAR-T second line.
  • Bispecifics as off-the-shelf T-cell therapy.
  • Frontline has moved: Pola-R-CHP (POLARIX) is standard for IPI 2-5, and frontMIND (tafasitamab-lenalidomide-R-CHOP) is the first phase 3 to beat R-CHOP in IPI 3-5 disease since rituximab.
  • Four CD20×CD3 bispecifics approved or conditionally approved worldwide give ~40% complete remissions off the shelf; chemotherapy-free doublets (mosun-pola) beat salvage chemotherapy.
  • ctDNA by phased-variant sequencing detects residual lymphoma below PET sensitivity and is entering response-adapted trials.
Show survival figures (2)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • CD19 CAR-T is second-line standard for early relapse, with an overall survival benefit in ZUMA-7 (4-year OS 54.6% vs 46.0%).
  • Regulators now scrutinise generalisability (STARGLO CRL) and demand overall survival for confirmatory bispecific trials (EPCORE DLBCL-1 missed OS).
Who it affects

~150,000 new cases a year worldwide; ~25,000 in the US; median age 65; about 60% cured with first-line therapy.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Non-Hodgkin lymphoma (all subtypes) (shared total; subtype split not reported). World: 553,389 new cases, 250,679 deaths.

#CountryNew casesDeaths
1China80,82939,700
2United States of America77,95620,827
3India39,73622,972
4Japan36,17915,408
5Germany18,9807,879
6France (metropolitan)16,9726,073
7Indonesia16,1759,440
8United Kingdom16,0475,671
9Italy15,5765,879
10Russian Federation12,0706,338

GLOBOCAN reports NHL as one site; DLBCL is roughly 30-40% of cases.

Standard of care

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Frontline

R-CHOP or Pola-R-CHP.

NCCN Guidelines: B-Cell Lymphomas
Early relapse

CD19 CAR-T.

NCCN Guidelines: B-Cell Lymphomas
Axicabtagene ciloleucel
Later

CD20×CD3 bispecifics, loncastuximab, tafasitamab.

NCCN Guidelines: B-Cell Lymphomas
GlofitamabLoncastuximab tesirine
Limited stage (I-II, non-bulky)

R-CHOP × 4 with PET-guided omission of radiation (FLYER, S1001): 4 cycles if interim PET negative; involved-site radiotherapy if PET positive.

NCCN · Category 1 (R-CHOP × 4 PET-adapted for stag…
DoxorubicinFDG PETIMRT / IGRT (modern external beam)Lugano classification / Ann Arbor staging
Advanced stage, IPI 0-1

R-CHOP × 6 (or Pola-R-CHP); consider 4 cycles plus 2 rituximab in young low-risk patients (FLYER).

NCCN · Category 1
DoxorubicinPolatuzumab vedotinInternational Prognostic Index (IPI)
Advanced stage, IPI 2-5

Pola-R-CHP × 6 (POLARIX) or R-CHOP × 6; tafasitamab + lenalidomide + R-CHOP (frontMIND) pending approval for IPI 3-5; DA-EPOCH-R for double-hit lymphoma; CNS prophylaxis for high CNS-IPI (contested).

NCCN · Pola-R-CHP category 1 for IPI 2-5
POLARIXPolatuzumab vedotinfrontMINDTafasitamabDouble-hit / high-grade B-cell lymphoma
Frail or elderly

R-mini-CHOP; epcoritamab-based regimens in trials for the elderly (EPCORE NHL-2 cohorts); tafasitamab-lenalidomide where transplant is never an option.

EpcoritamabTafasitamabLenalidomide
Primary refractory or relapse within 12 months

CD19 CAR-T (axi-cel or liso-cel) preferred over salvage chemotherapy and transplant (ZUMA-7, TRANSFORM); bridging therapy while manufacturing; bispecific ± chemotherapy if CAR-T unavailable.

NCCN · Category 1 (axi-cel, liso-cel)
Axicabtagene ciloleucelZUMA-7TRANSFORMCAR-T cell therapy
Late relapse (>12 months), transplant-eligible

Salvage chemotherapy (R-ICE, R-DHAP, R-GemOx) → high-dose therapy and autologous transplant if chemosensitive; CAR-T if not.

Autologous stem cell transplant (high-dose therapy)CAR-T cell therapy
Relapse, transplant-ineligible

CD20×CD3 bispecific (glofitamab, epcoritamab) or mosunetuzumab-polatuzumab (SUNMO); pola-BR; tafasitamab-lenalidomide; loncastuximab tesirine.

GlofitamabEpcoritamabMosunetuzumabPolatuzumab vedotinTafasitamabLoncastuximab tesirineSUNMO
Third line and beyond

CAR-T if not yet given; bispecific after CAR-T (active in CD19-negative relapse if CD20 retained); loncastuximab; zilovertamab vedotin (trial); allogeneic transplant in selected fit patients; clinical trials.

Axicabtagene ciloleucelGlofitamabEpcoritamabLoncastuximab tesirineZilovertamab vedotinwaveLINE-003

Subtypes & biomarkers

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Subtypes
Biomarkers clinicians test

Target prevalence in this cancer

Target / alterationPrevalenceSource
CD19
Loss in ~30% of CAR-T relapses
>95%
Wikipedia
CD20
>95%
Wikipedia
CD79b
95%
doi.org
CD47
>90%
Wikipedia
ROR1
30-50%
Wikipedia
BCL-2
~90% in follicular lymphoma t(14;18)
30-40%
Wikipedia
EZH2
Tazemetostat withdrawn March 2026
20-25%
Wikipedia

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 1976CHOP regimen introduced

    Cyclophosphamide, doxorubicin, vincristine, prednisone becomes the backbone for aggressive lymphoma.

    DoxorubicinCytotoxic chemotherapy
  2. 1993CHOP proves equal to more intensive regimens; IPI published
    International Prognostic Index (IPI)
  3. 1997Rituximab: first antibody for cancer
  4. 1997Rituximab: first monoclonal antibody approved for cancer
    CD20Monoclonal antibodies
  5. 2000Gene-expression profiling defines GCB and ABC subtypes
    Cell of origin (GCB vs ABC)
  6. 2002GELA LNH-98.5: R-CHOP improves survival over CHOP

    Rituximab added to CHOP raises cure rates by ~15 points; the standard for the next twenty years.

  7. 2014Lugano classification unifies PET-based staging and response
    Lugano classification / Ann Arbor stagingFDG PET
  8. 2017Axi-cel CAR-T approved
    Axicabtagene ciloleucel
  9. 2017Axi-cel: first CAR-T approved for large B-cell lymphoma (ZUMA-1)
    Axicabtagene ciloleucelCAR-T cell therapy
  10. 2019Polatuzumab vedotin approved with BR for relapsed disease
    Polatuzumab vedotin
  11. 2020Tafasitamab-lenalidomide (L-MIND) approved for transplant-ineligible relapse
    TafasitamabL-MIND
  12. 2021Loncastuximab tesirine approved; BELINDA fails while ZUMA-7 and TRANSFORM succeed
    Loncastuximab tesirineLOTIS-2BELINDAZUMA-7TRANSFORM
  13. 2022ZUMA-7: CAR-T beats transplant
  14. 2022POLARIX: first frontline improvement on R-CHOP in twenty years; CAR-T approved second line
    POLARIXPolatuzumab vedotinAxicabtagene ciloleucel
  15. 2023Glofitamab, epcoritamab approved
    Glofitamab
  16. 2023Glofitamab and epcoritamab approved: off-the-shelf T-cell redirection
    GlofitamabEpcoritamabEPCORE NHL-1
  17. 2024STARGLO shows OS benefit for glofitamab-GemOx; odronextamab approved in EU
    STARGLOOdronextamab
  18. 2025SUNMO positive (mosun-pola); FDA rejects STARGLO indication over applicability; POLARIX 5-year data
    SUNMOSTARGLOPOLARIX
  19. 2026frontMIND published in Lancet; EPCORE DLBCL-1 misses OS; frontline bispecific data (EPCORE DLBCL-2) at EHA
    frontMINDEPCORE DLBCL-1EPCORE DLBCL-2

Pipeline

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Phase 3ADC
Zilovertamab vedotin
ApprovedMonoclonal antibody (anti-CD19, Fc-enhanced)
Tafasitamab · Monjuvi
ApprovedBispecific T-cell engager (CD20×CD3)
Epcoritamab · Epkinly
Phase 3Molecular glue degrader (CELMoD, IKZF1/3)
Golcadomide
ApprovedBispecific T-cell engager (CD20×CD3)
Mosunetuzumab · Lunsumio
ApprovedBispecific T-cell engager (CD20×CD3)
Odronextamab · Lynozyfic (EU: Ordspono)
frontMINDEPCORE DLBCL-2GOLSEEK-1SUNMOwaveLINE-003ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)ctDNA-guided escalation and de-escalation in frontline DLBCLHead-to-head bispecific vs CAR-T in second-line LBCL

Open problems

  • Primary refractory disease.
  • CAR-T access and cost.
  • Primary refractory disease (~10-15%) still has poor outcomes even with CAR-T; CD19-negative and CD20-negative escape after targeted therapy.
  • No head-to-head comparison of bispecifics and CAR-T; sequencing is by access rather than evidence.
  • Overall survival is hard to demonstrate for bispecifics against chemotherapy with crossover and effective later lines (EPCORE DLBCL-1).
  • Trial generalisability: STARGLO's rejection shows regional enrolment can decide approvals.
  • CNS relapse: prophylaxis with high-dose methotrexate is of uncertain benefit and CNS-penetrant options are few.
  • Older and frail patients are underrepresented; R-mini-CHOP cure rates lag and cellular therapies carry toxicity.
  • Cost and access: CAR-T requires certified centres; bispecific CRS management needs infrastructure; lenalidomide-based triplets add expense.
  • Response-adapted therapy: interim PET is unreliable and ctDNA is not yet a regulatory endpoint.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Diffuse large B-cell lymphoma
condition: diffuse large B-cell lymphoma
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

BELINDAEPCORE DLBCL-1EPCORE DLBCL-2EPCORE NHL-1frontMINDGOLSEEK-1L-MINDLOTIS-2POLARIXSTARGLOSUNMOTRANSFORMwaveLINE-003ZUMA-7

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Diffuse large B-cell lymphoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 33 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example Cell of origin, Double-hit, CD19/CD20, ctDNA MRD, IPI / NCCN-IPI), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Germinal-centre B-cell-likevs activated B-cell-like, High-grade B-cell lymphoma with MYC and BCL2 rearrangements, LymphGen genetic subtypes: MCD, BN2, N1, EZB, ST2, A53.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Frontline

  1. For my situation (frontline), which of the standard options do you recommend and why?
    Why: Guideline options include: R-CHOP or Pola-R-CHP.

Early relapse

  1. For my situation (early relapse), which of the standard options do you recommend and why?
    Why: Guideline options include: CD19 CAR-T.
  2. Am I a candidate for Axicabtagene ciloleucel, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Later

  1. For my situation (later), which of the standard options do you recommend and why?
    Why: Guideline options include: CD20×CD3 bispecifics, loncastuximab, tafasitamab.
  2. Am I a candidate for Glofitamab, Loncastuximab tesirine, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Limited stage (I-II, non-bulky)

  1. For my situation (limited stage (i-ii, non-bulky)), which of the standard options do you recommend and why?
    Why: Guideline options include: R-CHOP × 4 with PET-guided omission of radiation (FLYER, S1001): 4 cycles if interim PET negative; involved-site radiotherapy if PET positive.
  2. Am I a candidate for Doxorubicin, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Advanced stage, IPI 0-1

  1. For my situation (advanced stage, ipi 0-1), which of the standard options do you recommend and why?
    Why: Guideline options include: R-CHOP × 6 (or Pola-R-CHP); consider 4 cycles plus 2 rituximab in young low-risk patients (FLYER).
  2. Am I a candidate for Doxorubicin, Polatuzumab vedotin, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Advanced stage, IPI 2-5

  1. For my situation (advanced stage, ipi 2-5), which of the standard options do you recommend and why?
    Why: Guideline options include: Pola-R-CHP × 6 (POLARIX) or R-CHOP × 6; tafasitamab + lenalidomide + R-CHOP (frontMIND) pending approval for IPI 3-5; DA-EPOCH-R for double-hit lymphoma; CNS prophylaxis for high CNS-IPI (contested).
  2. Am I a candidate for Polatuzumab vedotin, Tafasitamab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of POLARIX and frontMIND apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Frail or elderly

  1. For my situation (frail or elderly), which of the standard options do you recommend and why?
    Why: Guideline options include: R-mini-CHOP; epcoritamab-based regimens in trials for the elderly (EPCORE NHL-2 cohorts); tafasitamab-lenalidomide where transplant is never an option.
  2. Am I a candidate for Epcoritamab, Tafasitamab, Lenalidomide, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Primary refractory or relapse within 12 months

  1. For my situation (primary refractory or relapse within 12 months), which of the standard options do you recommend and why?
    Why: Guideline options include: CD19 CAR-T (axi-cel or liso-cel) preferred over salvage chemotherapy and transplant (ZUMA-7, TRANSFORM); bridging therapy while manufacturing; bispecific ± chemotherapy if CAR-T unavailable.
  2. Am I a candidate for Axicabtagene ciloleucel, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of ZUMA-7 and TRANSFORM apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Late relapse (>12 months), transplant-eligible

  1. For my situation (late relapse (>12 months), transplant-eligible), which of the standard options do you recommend and why?
    Why: Guideline options include: Salvage chemotherapy (R-ICE, R-DHAP, R-GemOx) → high-dose therapy and autologous transplant if chemosensitive; CAR-T if not.

Relapse, transplant-ineligible

  1. For my situation (relapse, transplant-ineligible), which of the standard options do you recommend and why?
    Why: Guideline options include: CD20×CD3 bispecific (glofitamab, epcoritamab) or mosunetuzumab-polatuzumab (SUNMO); pola-BR; tafasitamab-lenalidomide; loncastuximab tesirine.
  2. Am I a candidate for Glofitamab, Epcoritamab, Mosunetuzumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of SUNMO apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Third line and beyond

  1. For my situation (third line and beyond), which of the standard options do you recommend and why?
    Why: Guideline options include: CAR-T if not yet given; bispecific after CAR-T (active in CD19-negative relapse if CD20 retained); loncastuximab; zilovertamab vedotin (trial); allogeneic transplant in selected fit patients; clinical trials.
  2. Am I a candidate for Axicabtagene ciloleucel, Glofitamab, Epcoritamab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of waveLINE-003 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Any stage

  1. Are there clinical trials I could join, for example of Zilovertamab vedotin, frontMIND, Tafasitamab, EPCORE DLBCL-2?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. 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.
  3. 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.
  4. I read that “Primary refractory disease”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “CAR-T access and cost”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

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Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

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Allogeneic stem cell transplantationAntibody-drug conjugate (ADC)Autologous stem cell transplant (high-dose therapy)CAR-T cell therapyCardio-oncologyctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)Cytotoxic chemotherapyExercise during chemotherapy and radiotherapyFDG PETIMRT / IGRT (modern external beam)In situ vaccinationMonoclonal antibodiesPET-adapted (response-adapted) therapyPROTACs & molecular glues (targeted protein degradation)Small-molecule kinase inhibitorsT-cell engagers (bispecific)Topoisomerase-I inhibitors (and ADC payloads)

targets

13
BCL-2BTK (Bruton tyrosine kinase)CD19CD20CD22CD3CD30CD47CD79bEZH2KMT2A (MLL) rearrangementROR1TP53

drugs

27
ApprovedSmall-molecule covalent BTK inhibitor (second generation)
Acalabrutinib · Calquence
ApprovedCAR-T (CD19)
Axicabtagene ciloleucel · Yescarta
Phase 3Small-molecule BTK degrader (CDAC)
BGB-16673
Not mapped hereAlkylating agent (oxazaphosphorine prodrug)
Cyclophosphamide · Cytoxan / Endoxan
ApprovedCytotoxic chemotherapy (anthracycline)
Doxorubicin · Adriamycin
ApprovedBispecific T-cell engager (CD20×CD3)
Epcoritamab · Epkinly
Not mapped hereTopoisomerase II inhibitor (podophyllotoxin derivative)
Etoposide · VePesid / Etopophos / Toposar
ApprovedBispecific T-cell engager (CD20×CD3, 2:1)
Glofitamab · Columvi
Phase 3Molecular glue degrader (CELMoD, IKZF1/3)
Golcadomide
ApprovedSmall-molecule covalent BTK inhibitor (first generation)
Ibrutinib · Imbruvica
ApprovedImmunomodulatory drug (cereblon E3 ligase modulator)
Lenalidomide · Revlimid
ApprovedCAR-T (CD19, defined CD4:CD8)
Lisocabtagene maraleucel · Breyanzi
ApprovedADC
Loncastuximab tesirine · Zynlonta
Not mapped hereAntifolate (DHFR inhibitor)
Methotrexate · Trexall / Otrexup / Xatmep
ApprovedBispecific T-cell engager (CD20×CD3)
Mosunetuzumab · Lunsumio
ApprovedMonoclonal antibody (anti-CD20, glycoengineered type II)
Obinutuzumab · Gazyva
ApprovedBispecific T-cell engager (CD20×CD3)
Odronextamab · Lynozyfic (EU: Ordspono)
ApprovedSmall-molecule non-covalent (reversible) BTK inhibitor
Pirtobrutinib · Jaypirca
ApprovedADC
Polatuzumab vedotin · Polivy
ApprovedMonoclonal antibody (anti-CD20, chimeric)
Rituximab · Rituxan / MabThera (and biosimilars)
ApprovedSmall-molecule XPO1 (nuclear export) inhibitor
Selinexor · Xpovio
ApprovedSmall-molecule BCL-2 inhibitor (second generation)
Sonrotoclax · Beqalzi
ApprovedMonoclonal antibody (anti-CD19, Fc-enhanced)
Tafasitamab · Monjuvi
ApprovedCAR-T (CD19)
Tisagenlecleucel · Kymriah
Not mapped hereVinca alkaloid (microtubule inhibitor)
Vincristine · Oncovin / Marqibo
ApprovedSmall-molecule covalent BTK inhibitor (second generation)
Zanubrutinib · Brukinsa
Phase 3ADC
Zilovertamab vedotin

companies

26
AbbVie (incl. ImmunoGen, Capstan)ADC TherapeuticsAllogene TherapeuticsAraris Biotech (Taiho)AstraZenecaBeOne Medicines (formerly BeiGene)Bristol Myers SquibbCaribou BiosciencesEli Lilly (incl. Loxo)Fate TherapeuticsForesight DiagnosticsGenmabGilead Sciences (incl. Kite)IncyteInterius BioTherapeuticsJohnson & JohnsonKaryopharm TherapeuticsMerck & Co. (MSD)MorphoSys (Novartis)NkartaNovartisNurix TherapeuticsRegeneronRoche / GenentechSana BiotechnologyUmoja Biopharma

institutions

61
Advanced Centre for Treatment, Research and Education in CancerAmerican Society of HematologyBarts Cancer Institute / Barts Health NHS TrustBC CancerButaro Cancer Center of ExcellenceCharlotte Maxeke Johannesburg Academic Hospital / University of the WitwatersrandChinese PLA General HospitalCleveland Clinic Abu DhabiComprehensive Cancer Center Mainfranken, University Hospital WürzburgComprehensive Cancer Center Vienna – Medical University of Vienna / AKHDana-Farber Brigham Cancer CenterEuropean Hematology AssociationFred & Pamela Buffett Cancer CenterGeneva University Hospitals (HUG)German Lymphoma AllianceGustave RoussyHadassah Medical CenterHamad Medical Corporation / National Center for Cancer Care and ResearchHenan Cancer HospitalHerbert Irving Comprehensive Cancer Center, Columbia UniversityHOVONHUS Comprehensive Cancer Center, Helsinki University HospitalInstitut Jules BordetInstituto Nacional de Cancerología (Mexico)International Extranodal Lymphoma Study GroupIRCCS Azienda Ospedaliero-Universitaria di Bologna – Policlinico Sant'OrsolaIRCCS Humanitas Research HospitalKeio University HospitalKenyatta National HospitalKing Faisal Specialist Hospital and Research CentreKing Hussein Cancer CenterKoo Foundation Sun Yat-Sen Cancer CenterKyushu University HospitalLeeds Cancer Centre, St James's University HospitalLYSA – The Lymphoma Study AssociationMax Delbrück Center for Molecular MedicineMayo ClinicMD Anderson Cancer CenterMemorial Sloan Kettering Cancer CenterNational Cancer Institute, Cairo UniversityNational University Hospital / National University Cancer Institute, SingaporeNCI Center for Cancer Research (intramural programme)Nordic Lymphoma GroupPeking University Cancer HospitalRajiv Gandhi Cancer Institute and Research CentreRigshospitalet – Copenhagen University HospitalRuijin Hospital, Shanghai Jiao Tong UniversitySeoul St. Mary's HospitalSheba Medical CenterTata Medical Center, KolkataThe Christie NHS Foundation TrustThe Ottawa Hospital Cancer Centre / Ottawa Hospital Research InstituteTongji Hospital, Huazhong University of Science and TechnologyUganda Cancer InstituteUNC Lineberger Comprehensive Cancer CenterUnion Hospital, Tongji Medical CollegeUniversity Cancer Center Frankfurt (UCT)University College London Hospitals / UCL Cancer InstituteUniversity Hospital Southampton / Centre for Cancer ImmunologyUniversity Hospital Zurich / Comprehensive Cancer Center ZurichWilmot Cancer Institute, University of Rochester

pathways

2
Intrinsic apoptosis (BCL-2 family)MYC

terms

11
B cellCell of origin (GCB vs ABC)Cytokine release syndrome (CRS)Deauville five-point scaleDouble-hit / high-grade B-cell lymphomaICANS (neurotoxicity)International Prognostic Index (IPI)Lugano classification / Ann Arbor stagingLymphoma (tissue type)Minimal / molecular residual disease (MRD)Richter transformation

trials

14
BELINDAEPCORE DLBCL-1EPCORE DLBCL-2EPCORE NHL-1frontMINDGOLSEEK-1L-MINDLOTIS-2POLARIXSTARGLOSUNMOTRANSFORMwaveLINE-003ZUMA-7

pairings

3
Caution: cumulative anthracycline dose and the heartCD20 bispecific + CD79b ADC (mosunetuzumab + polatuzumab)Early relapse: CAR-T before transplant

ideas

18
A funded expert second opinion for every new high-stakes or rare cancer diagnosisA risk-stratified cardio-oncology pathway for everyone receiving heart-toxic cancer therapyBiomarker-guided cardioprotection for everyone on cardiotoxic cancer therapyCollect and freeze T cells at diagnosis for high-risk patients, before chemotherapyctDNA-guided escalation and de-escalation in frontline DLBCLHead-to-head bispecific vs CAR-T in second-line LBCLHospital-based CAR-T manufacturing at cost through a public networkHospital-made CAR-T under one shared regulatory master fileIn vivo CAR-T as a vial on the shelf: a cost and access trial in lymphomaIn vivo CAR-T manufactured and priced like a generic biologicNon-viral CAR-T (transposon or CRISPR knock-in) as the default manufacturing routeOutcome-based annuity payments for potentially curative one-time therapiesPet dogs with spontaneous cancer as a bridge before human trialsPlan the second CAR-T target before the first one is lostPublic-sector CAR-T manufacturing in India, Brazil and South Africa under $50,000Read the spinal fluid to track brain tumours without opening the skullTurn one tumour into a vaccine to treat all the othersWHO prequalification plus pooled demand to push biosimilar prices below 10% of the originator

collections

2
Leukemia & Lymphoma Society (LLS)Lymphoma Research Foundation (LRF)

people

15
Alex F. HerreraAsh A. AlizadehCarl H. JuneChristopher R. FlowersFrederick L. LockeIrving L. WeissmanJoshua BrodyLouis M. StaudtMichael A. TeitellRonald LevyStanley R. RiddellStephen J. FormanSteven Le GouillSteven T. RosenYuankai Shi

bottlenecks

3
Acquired resistance to every therapyManufacturing cost and time for living and radioactive medicinesOlder and multimorbid patients are excluded and undertreated

key papers

6
EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-TJULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphomaPOLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphomaTRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphomaZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphomaZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early

Key papers

6top
translationalJournal of Clinical Oncology 2023changed practice
EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-T

CD20 x CD3 bispecifics gave patients whose lymphoma has failed CAR-T, or who cannot access it, an effective off-the-shelf treatment that can be started within days. Epcoritamab and glofitamab are now standard third-line options and are moving into earlier lines and combinations. They do not yet replace CAR-T, whose remissions appear more durable.

rctNew England Journal of Medicine 2022changed practice
POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma

POLARIX gave the first new first-line standard for DLBCL since rituximab was added to CHOP, and pola-R-CHP is now approved and widely used, especially in higher-risk or ABC-type disease. The gain is modest and survival is unchanged, so many clinicians still use R-CHOP in lower-risk or GCB-type patients. Cost and subgroup uncertainty drive ongoing debate.

rctThe Lancet 2022changed practice
TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma

TRANSFORM confirmed ZUMA-7's conclusion with a different CD19 CAR-T and a more permissive design that allowed bridging chemotherapy, making the results closer to real-world practice. Liso-cel's low toxicity makes it attractive for older or frailer patients and for outpatient delivery. Together the two trials made CAR-T the standard second-line therapy for early-relapsing aggressive lymphoma.

rctNew England Journal of Medicine 2022changed practice
ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early

ZUMA-7 rewrote second-line treatment for aggressive lymphoma: patients whose disease returns within a year of R-CHOP should be offered CAR-T rather than salvage chemotherapy and transplant. It is also one of the few cell-therapy trials to show an overall survival benefit despite crossover. Patients relapsing later than 12 months were not studied and transplant remains standard for them if chemosensitive.

translationalNew England Journal of Medicine 2019changed practice
JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma

JULIET, with ZUMA-1, showed that CAR-T could rescue a substantial minority of adults with chemotherapy-refractory lymphoma and that complete responders often stay in remission. The lower toxicity of a 4-1BB construct and the option of bridging therapy made it usable in a broader population. The high drop-out between enrolment and infusion remains a lesson about turnaround time.

translationalNew England Journal of Medicine 2017changed practice
ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma

ZUMA-1 showed that CAR-T can cure a meaningful fraction of adults whose aggressive lymphoma no longer responds to chemotherapy, a group with a historical median survival of about six months (SCHOLAR-1). Axi-cel became the first CAR-T approved for lymphoma and later the first to beat standard second-line therapy in ZUMA-7. The comparatively high neurotoxicity of CD28-costimulated products was also first characterised here.

Latest papers

top
Literature trend1,619 papers in the last 12 months+3% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Diffuse large B-cell lymphoma" OR ABSTRACT:"Diffuse large B-cell lymphoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Diffuse large B-cell lymphoma, not a curated reading list.

Connected

207top

technologies

13
Antibody-drug conjugate (ADC)Autologous stem cell transplant (high-dose therapy)CAR-T cell therapyctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)Cytotoxic chemotherapyExercise during chemotherapy and radiotherapyFDG PETIMRT / IGRT (modern external beam)In situ vaccinationMonoclonal antibodiesPET-adapted (response-adapted) therapyPROTACs & molecular glues (targeted protein degradation)T-cell engagers (bispecific)

targets

11
BCL-2BTK (Bruton tyrosine kinase)CD19CD20CD22CD3CD30CD47CD79bEZH2ROR1

drugs

27
ApprovedSmall-molecule covalent BTK inhibitor (second generation)
Acalabrutinib · Calquence
ApprovedCAR-T (CD19)
Axicabtagene ciloleucel · Yescarta
Phase 3Small-molecule BTK degrader (CDAC)
BGB-16673
Not mapped hereAlkylating agent (oxazaphosphorine prodrug)
Cyclophosphamide · Cytoxan / Endoxan
ApprovedCytotoxic chemotherapy (anthracycline)
Doxorubicin · Adriamycin
ApprovedBispecific T-cell engager (CD20×CD3)
Epcoritamab · Epkinly
Not mapped hereTopoisomerase II inhibitor (podophyllotoxin derivative)
Etoposide · VePesid / Etopophos / Toposar
ApprovedBispecific T-cell engager (CD20×CD3, 2:1)
Glofitamab · Columvi
Phase 3Molecular glue degrader (CELMoD, IKZF1/3)
Golcadomide
ApprovedSmall-molecule covalent BTK inhibitor (first generation)
Ibrutinib · Imbruvica
ApprovedImmunomodulatory drug (cereblon E3 ligase modulator)
Lenalidomide · Revlimid
ApprovedCAR-T (CD19, defined CD4:CD8)
Lisocabtagene maraleucel · Breyanzi
ApprovedADC
Loncastuximab tesirine · Zynlonta
Not mapped hereAntifolate (DHFR inhibitor)
Methotrexate · Trexall / Otrexup / Xatmep
ApprovedBispecific T-cell engager (CD20×CD3)
Mosunetuzumab · Lunsumio
ApprovedMonoclonal antibody (anti-CD20, glycoengineered type II)
Obinutuzumab · Gazyva
ApprovedBispecific T-cell engager (CD20×CD3)
Odronextamab · Lynozyfic (EU: Ordspono)
ApprovedSmall-molecule non-covalent (reversible) BTK inhibitor
Pirtobrutinib · Jaypirca
ApprovedADC
Polatuzumab vedotin · Polivy
ApprovedMonoclonal antibody (anti-CD20, chimeric)
Rituximab · Rituxan / MabThera (and biosimilars)
ApprovedSmall-molecule XPO1 (nuclear export) inhibitor
Selinexor · Xpovio
ApprovedSmall-molecule BCL-2 inhibitor (second generation)
Sonrotoclax · Beqalzi
ApprovedMonoclonal antibody (anti-CD19, Fc-enhanced)
Tafasitamab · Monjuvi
ApprovedCAR-T (CD19)
Tisagenlecleucel · Kymriah
Not mapped hereVinca alkaloid (microtubule inhibitor)
Vincristine · Oncovin / Marqibo
ApprovedSmall-molecule covalent BTK inhibitor (second generation)
Zanubrutinib · Brukinsa
Phase 3ADC
Zilovertamab vedotin

companies

21
AbbVie (incl. ImmunoGen, Capstan)ADC TherapeuticsAllogene TherapeuticsAraris Biotech (Taiho)Bristol Myers SquibbCaribou BiosciencesFate TherapeuticsForesight DiagnosticsGenmabGilead Sciences (incl. Kite)IncyteInterius BioTherapeuticsMerck & Co. (MSD)MorphoSys (Novartis)NkartaNovartisNurix TherapeuticsRegeneronRoche / GenentechSana BiotechnologyUmoja Biopharma

institutions

61
Advanced Centre for Treatment, Research and Education in CancerAmerican Society of HematologyBarts Cancer Institute / Barts Health NHS TrustBC CancerButaro Cancer Center of ExcellenceCharlotte Maxeke Johannesburg Academic Hospital / University of the WitwatersrandChinese PLA General HospitalCleveland Clinic Abu DhabiComprehensive Cancer Center Mainfranken, University Hospital WürzburgComprehensive Cancer Center Vienna – Medical University of Vienna / AKHDana-Farber Brigham Cancer CenterEuropean Hematology AssociationFred & Pamela Buffett Cancer CenterGeneva University Hospitals (HUG)German Lymphoma AllianceGustave RoussyHadassah Medical CenterHamad Medical Corporation / National Center for Cancer Care and ResearchHenan Cancer HospitalHerbert Irving Comprehensive Cancer Center, Columbia UniversityHOVONHUS Comprehensive Cancer Center, Helsinki University HospitalInstitut Jules BordetInstituto Nacional de Cancerología (Mexico)International Extranodal Lymphoma Study GroupIRCCS Azienda Ospedaliero-Universitaria di Bologna – Policlinico Sant'OrsolaIRCCS Humanitas Research HospitalKeio University HospitalKenyatta National HospitalKing Faisal Specialist Hospital and Research CentreKing Hussein Cancer CenterKoo Foundation Sun Yat-Sen Cancer CenterKyushu University HospitalLeeds Cancer Centre, St James's University HospitalLYSA – The Lymphoma Study AssociationMax Delbrück Center for Molecular MedicineMayo ClinicMD Anderson Cancer CenterMemorial Sloan Kettering Cancer CenterNational Cancer Institute, Cairo UniversityNational University Hospital / National University Cancer Institute, SingaporeNCI Center for Cancer Research (intramural programme)Nordic Lymphoma GroupPeking University Cancer HospitalRajiv Gandhi Cancer Institute and Research CentreRigshospitalet – Copenhagen University HospitalRuijin Hospital, Shanghai Jiao Tong UniversitySeoul St. Mary's HospitalSheba Medical CenterTata Medical Center, KolkataThe Christie NHS Foundation TrustThe Ottawa Hospital Cancer Centre / Ottawa Hospital Research InstituteTongji Hospital, Huazhong University of Science and TechnologyUganda Cancer InstituteUNC Lineberger Comprehensive Cancer CenterUnion Hospital, Tongji Medical CollegeUniversity Cancer Center Frankfurt (UCT)University College London Hospitals / UCL Cancer InstituteUniversity Hospital Southampton / Centre for Cancer ImmunologyUniversity Hospital Zurich / Comprehensive Cancer Center ZurichWilmot Cancer Institute, University of Rochester

pathways

2
Intrinsic apoptosis (BCL-2 family)MYC

terms

11
B cellCell of origin (GCB vs ABC)Cytokine release syndrome (CRS)Deauville five-point scaleDouble-hit / high-grade B-cell lymphomaICANS (neurotoxicity)International Prognostic Index (IPI)Lugano classification / Ann Arbor stagingLymphoma (tissue type)Minimal / molecular residual disease (MRD)Richter transformation

trials

14
BELINDAEPCORE DLBCL-1EPCORE DLBCL-2EPCORE NHL-1frontMINDGOLSEEK-1L-MINDLOTIS-2POLARIXSTARGLOSUNMOTRANSFORMwaveLINE-003ZUMA-7

pairings

3
Caution: cumulative anthracycline dose and the heartCD20 bispecific + CD79b ADC (mosunetuzumab + polatuzumab)Early relapse: CAR-T before transplant

ideas

18
A funded expert second opinion for every new high-stakes or rare cancer diagnosisA risk-stratified cardio-oncology pathway for everyone receiving heart-toxic cancer therapyBiomarker-guided cardioprotection for everyone on cardiotoxic cancer therapyCollect and freeze T cells at diagnosis for high-risk patients, before chemotherapyctDNA-guided escalation and de-escalation in frontline DLBCLHead-to-head bispecific vs CAR-T in second-line LBCLHospital-based CAR-T manufacturing at cost through a public networkHospital-made CAR-T under one shared regulatory master fileIn vivo CAR-T as a vial on the shelf: a cost and access trial in lymphomaIn vivo CAR-T manufactured and priced like a generic biologicNon-viral CAR-T (transposon or CRISPR knock-in) as the default manufacturing routeOutcome-based annuity payments for potentially curative one-time therapiesPet dogs with spontaneous cancer as a bridge before human trialsPlan the second CAR-T target before the first one is lostPublic-sector CAR-T manufacturing in India, Brazil and South Africa under $50,000Read the spinal fluid to track brain tumours without opening the skullTurn one tumour into a vaccine to treat all the othersWHO prequalification plus pooled demand to push biosimilar prices below 10% of the originator

collections

2
Leukemia & Lymphoma Society (LLS)Lymphoma Research Foundation (LRF)

people

15
Alex F. HerreraAsh A. AlizadehCarl H. JuneChristopher R. FlowersFrederick L. LockeIrving L. WeissmanJoshua BrodyLouis M. StaudtMichael A. TeitellRonald LevyStanley R. RiddellStephen J. FormanSteven Le GouillSteven T. RosenYuankai Shi

bottlenecks

3
Acquired resistance to every therapyManufacturing cost and time for living and radioactive medicinesOlder and multimorbid patients are excluded and undertreated

key papers

6
EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-TJULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphomaPOLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphomaTRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphomaZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphomaZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early