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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| 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) |
| 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 |
| 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 |
| 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. | not mapped |
| 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) |
| 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. | not mapped |
| Relapse, transplant-ineligible | CD20×CD3 bispecific (glofitamab, epcoritamab) or mosunetuzumab-polatuzumab (SUNMO); pola-BR; tafasitamab-lenalidomide; loncastuximab tesirine. | not mapped |
| 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. | not mapped |