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.
Overview
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
- 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).
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
- Bone marrow (leukaemia, MDS, MPN, myeloma)Germinal-centre B-cell-like (GCB) vs activated B-cell-like (ABC / non-GCB) · High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double hit) · Primary mediastinal B-cell lymphoma (distinct; PD-1 responsive) · Transformed indolent lymphoma (Richter, transformed follicular)
- Lymph node germinal centre (lymphomas)Germinal-centre B-cell-like (GCB) vs activated B-cell-like (ABC / non-GCB) · High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double hit) · Transformed indolent lymphoma (Richter, transformed follicular) · EBV-positive DLBCL of the elderly
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sitesPrimary mediastinal B-cell lymphoma (distinct; PD-1 responsive) · Primary CNS lymphoma (distinct; methotrexate-based)
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: Follicular lymphoma
Preclinical models
9 cell lines, 1 mouse models and 2 repositories are listed for this cancer.
~150,000 new cases a year worldwide; ~25,000 in the US; median age 65; about 60% cured with first-line therapy.
R-CHOP × 4 with PET-guided omission of radiation (FLYER, S1001): 4 cycles if interim PET negative; involved-site radiotherapy if PET positive.
R-CHOP × 6 (or Pola-R-CHP); consider 4 cycles plus 2 rituximab in young low-risk patients (FLYER).
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).
R-mini-CHOP; epcoritamab-based regimens in trials for the elderly (EPCORE NHL-2 cohorts); tafasitamab-lenalidomide where transplant is never an option.
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.
Salvage chemotherapy (R-ICE, R-DHAP, R-GemOx) → high-dose therapy and autologous transplant if chemosensitive; CAR-T if not.
CD20×CD3 bispecific (glofitamab, epcoritamab) or mosunetuzumab-polatuzumab (SUNMO); pola-BR; tafasitamab-lenalidomide; loncastuximab tesirine.
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.
Subtypes & biomarkers
top- Germinal-centre B-cell-like (GCB) vs activated B-cell-like (ABC / non-GCB)
- High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double hit)
- LymphGen genetic subtypes : MCD, BN2, N1, EZB, ST2, A53
- Primary mediastinal B-cell lymphoma (distinct; PD-1 responsive)
- Primary CNS lymphoma (distinct; methotrexate-based)
- Transformed indolent lymphoma (Richter, transformed follicular)
- EBV-positive DLBCL of the elderly
- Primary refractory vs early relapse (<12 months) vs late relapse
- Cell of origin (GCB/ABC)
- Double-hit (MYC/BCL2)
- CD19/CD20
- ctDNA MRD
- IPI / NCCN-IPI
- Cell of origin (Hans IHC, Lymph2Cx)
- MYC, BCL2, BCL6 FISH
- TP53 mutation
- CD19 and CD20 expression (loss after CAR-T or bispecific)
- Interim and end-of-treatment PET (Deauville)
- ctDNA (PhasED-seq, clonoSEQ)
- LDH
- CNS-IPI for CNS prophylaxis decisions
How often this target appears
- 1976CHOP regimen introduced
Cyclophosphamide, doxorubicin, vincristine, prednisone becomes the backbone for aggressive lymphoma.
- 1993CHOP proves equal to more intensive regimens; IPI published
- 1997Rituximab: first antibody for cancer
- 1997Rituximab: first monoclonal antibody approved for cancer
- 2000Gene-expression profiling defines GCB and ABC subtypes
- 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.
- 2014Lugano classification unifies PET-based staging and response
- 2017Axi-cel CAR-T approved
- 2017Axi-cel: first CAR-T approved for large B-cell lymphoma (ZUMA-1)
- 2019Polatuzumab vedotin approved with BR for relapsed disease
- 2020Tafasitamab-lenalidomide (L-MIND) approved for transplant-ineligible relapse
- 2021Loncastuximab tesirine approved; BELINDA fails while ZUMA-7 and TRANSFORM succeed
- 2022ZUMA-7: CAR-T beats transplant
- 2022POLARIX: first frontline improvement on R-CHOP in twenty years; CAR-T approved second line
- 2023Glofitamab, epcoritamab approved
- 2023Glofitamab and epcoritamab approved: off-the-shelf T-cell redirection
- 2024STARGLO shows OS benefit for glofitamab-GemOx; odronextamab approved in EU
- 2025SUNMO positive (mosun-pola); FDA rejects STARGLO indication over applicability; POLARIX 5-year data
- 2026frontMIND published in Lancet; EPCORE DLBCL-1 misses OS; frontline bispecific data (EPCORE DLBCL-2) at EHA
Dated changes read from the records linked to this indication: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 26 changes by month →- 2026-09-07This recordDiffuse large B-cell lymphomaFacts on this page last checked
When this page itself was last checked or edited.
- 2026GuidelineDiffuse large B-cell lymphomaGuideline NCCN 2026: 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)
- 2026GuidelineDiffuse large B-cell lymphomaGuideline NCCN 2026: 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)
- 2026GuidelineDiffuse large B-cell lymphomaGuideline NCCN 2026: 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))
- 2026GuidelineDiffuse large B-cell lymphomaGuideline NCCN B-Cell Lymphomas 2026: 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 stage I-II))
- 2026MilestoneDiffuse large B-cell lymphomafrontMIND published in Lancet; EPCORE DLBCL-1 misses OS; frontline bispecific data (EPCORE DLBCL-2) at EHA
A milestone in how this cancer is treated.
What is in development for Diffuse large B-cell lymphoma, drawn from the whole corpus: 2 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials under way · 1
- Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom · phase 2 · Cellectar Biosciences, Inc.
Combinations being explored · 1
Open problems and what is being done
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
topTrials recruiting now
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Landmark trials
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
2targets
1drugs
1companies
3institutions
10terms
1trials
1pairings
1bottlenecks
1Latest papers
topQuery for this indication: (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.
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