Diffuse large B-cell lymphoma: lines of therapy

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11 standard-of-care settings across 6 lines and 2 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

Line	All comers	FRα
Locally advanced	1	·
Advanced, first line	3	·
Second line	3	·
Third line and beyond	1	1
Special situations	·	1
Other settings	1	·

Locally advanced

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	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.	DoxorubicinFDG PETIMRT / IGRT (modern external beam)Lugano classification / Ann Arbor staging	NCCN · Category 1 (R-CHOP × 4 PET-adapted for stag…	91

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Frontline	R-CHOP or Pola-R-CHP.		NCCN Guidelines: B-Cell Lymphomas	—
All comers	Advanced stage, IPI 0-1	R-CHOP × 6 (or Pola-R-CHP); consider 4 cycles plus 2 rituximab in young low-risk patients (FLYER).	DoxorubicinPolatuzumab vedotinInternational Prognostic Index (IPI)	NCCN · Category 1	83
All comers	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).	POLARIXPolatuzumab vedotinfrontMINDTafasitamabDouble-hit / high-grade B-cell lymphoma	NCCN · Pola-R-CHP category 1 for IPI 2-5	89

Second line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Early relapse	CD19 CAR-T.	Axicabtagene ciloleucel	NCCN Guidelines: B-Cell Lymphomas	82
All comers	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		89
All comers	Relapse, transplant-ineligible	CD20×CD3 bispecific (glofitamab, epcoritamab) or mosunetuzumab-polatuzumab (SUNMO); pola-BR; tafasitamab-lenalidomide; loncastuximab tesirine.	GlofitamabEpcoritamabMosunetuzumabPolatuzumab vedotinTafasitamabLoncastuximab tesirineSUNMO		83

Third line and beyond

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	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		82
FRα	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.	Axicabtagene ciloleucelZUMA-7TRANSFORMCAR-T cell therapy	NCCN · Category 1 (axi-cel, liso-cel)	89

Special situations

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
FRα	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		87

Other settings

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Later	CD20×CD3 bispecifics, loncastuximab, tafasitamab.	GlofitamabLoncastuximab tesirine	NCCN Guidelines: B-Cell Lymphomas	72

Sequence and caution pairings

SequenceApproved

Early relapse: CAR-T before transplant

If large B-cell lymphoma comes back within a year, CAR-T should come before, not after, a transplant attempt.

CautionApproved

Caution: cumulative anthracycline dose and the heart

Every dose of doxorubicin adds to a lifetime total; above roughly 450 mg/m2 heart failure risk rises steeply, so sarcoma and lymphoma regimens are capped and hearts are monitored.

Regimens in the library

R-CHOP Pola-R-CHP R-ICE Fludarabine + cyclophosphamide lymphodepletion, then CD19 CAR-T

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.