Diffuse Large B-Cell Lymphoma (DLBCL) Guidelines

Updated: Jul 20, 2023
  • Author: Shipra Gandhi, MBBS; Chief Editor: Emmanuel C Besa, MD  more...
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Guidelines Summary

Guidelines on diffuse large B-cell lymphoma (DLBCL) have been published by the National Comprehensive Cancer Network (NCCN) [73] and the European Society for Medical Oncology (ESMO). [75]


In addition to its general guidance on diagnosis of lymphoma, the NCCN recommends the following studies to establish a diagnosis of DLBCL\\ [73] :

  • Immunohistochemistry (IHC) panel: CD20, CD3, CD5, CD10, CD45, BCL2, BCL6, Ki-67, IRF4/MUM1, MYC
  • Cell surface marker analysis by flow cytometry: kappa/lambda, CD45, CD3, CD5, CD19, CD10, CD20
  • Additional IHC panel for subtyping: Cyclin D1, kappa/lambda, CD30, CD138, EBER-ISH, ALK, HHV8
  • Fluorescence in situ hybridization (FISH) or cytogenetics for detection of t(14;18),  t(3;v),  t(8;14),  t(8;v)

IHC should include adequate markers to differentiate the two subtypes of DLBCL: activated B-cell type (ABC) and germinal center B-cell type (GCB). The subtypes are genetically different diseases, and survival in patients with the ABC subtype is worse than in those with GCB.

Risk stratification

The NCCN and ESMO recommend use of the International prognostic index (IPI) for all patients. Age-adjusted International Prognostic Index (aa-IPI) should be used for risk stratification of patients aged 60 years and younger. [73, 75]

The IPI includes the following risk factors:

  • Age > 60 years
  • Elevated serum lactate dehydrogenase (LDH) level
  • Eastern Cooperative Oncology Group (ECOG) performance status ≥2
  • Stage III or IV disease
  • Extranodal involvement > 1 site

Each risk factor is worth 1 point. On the basis of the IPI score, patients can be categorized as follows:

  • Low risk (0-1 point)
  • Low-intermediate risk (2 points)
  • High-intermediate risk (3 points)
  • High risk (4-5 points)

The aa-IPI includes the following risk factors (1 point is allotted for each factor):

  • Elevated LDH level
  • Stage III or IV disease
  • ECOG performance status ≥2

Based on the aa-IPI score, patients can be categorized as follows:

  • Low risk (0 points)
  • Low-intermediate risk (1 point)
  • High-intermediate risk (2 points)
  • High risk (3 points)


National Comprehensive Cancer Network recommendations

NCCN treatment recommendations for stage I/II (nonbulky) disease are as follows [73] :

  • R-CHOP (rituximab, cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisone) for three cycles, then restage with PET/CT
  • In patients with complete response, add a cycle of R-CHOP (for a total of four cycles) or involved-site radiation therapy (ISRT)
  • In patients with partial response, add one to three cycles of R-CHOP (total of four to six cycles) with or without ISRT, or ISRT

For stage II DLBCL with extensive mesenteric disease and stage III/IV DLBCL, NCCN preferred regimens for first-line therapy are as follows [73] :

  • R-CHOP
  • Pola-R-CHP (polatuzumab vedotin-piiq, rituximab, cyclophosphamide, doxorubicin, prednisone), if IPI ≥2
  • Other regimens that may be considered include dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) plus rituximab

  • In patients at increased risk for central nervous system relapse (eg, disease involving the paranasal sinus, testis, epidural, bone marrow, HIV lymphoma, kidney or adrenal involvement or > 2 extranodal sites, elevated LDH or concomitant expression of BCL2 and MYC protein), four to eight doses of intrathecal methotrexate and/or cytarabine, or 3-3.5 g/m2 of systemic methotrexate for prophylaxis is recommended.

For relapse that occurs less than 12 months after first-line therapy,  or primary refractory disease, the NCCN recommends anti-CD19 chimeric antigen receptor (CAR) T-cell therapy with one of the following:

  • Axicabtagene ciloleucel
  • Lisocabtagene maraleucel

For other relapsed or refractory disease, preferred second-line regimens when there is intention to proceed with transplant include the following:

  • DHA (dexamethasone, cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) ± rituximab
  • GDP (gemcitabine, dexamethasone, cisplatin or carboplatin) ± rituximab
  • ICE (ifosfamide, carboplatin, etoposide) ± rituximab

Preferred second-line regimens when there is no intention to proceed with transplant include the following:

  • Anti-CD19 CAR T-cell therapy with lisocabtagene maraleucel
  • Polatuzumab vedotin-piiq ± bendamustine ± rituximab
  • Tafasitamab-cxix m + lenalidomide

For third-line and subsequent therapy, recommended regimens are as follows:

  • Anti-CD19 CAR T-cell therapy, if not previousliy given
  • Epcoritamab-bys
  • Glofitamab-gxbm
  • Loncastuximab tesirine-lpyl
  • Selinex

European Society for Medical Oncology recommendations

The ESMO guidelines contain specific recommendations for patients < 60 years old based on aaIPI risk. [75]

For aa-IPI=0 without bulky disease, treatment recommendations are as follows:

  • R-CHOP every 21 d for six cycles is preferred
  • Radiation therapy has no proven benefit

For aa-IPI=0 with bulky disease or aa-IPI=1, treatment recommendations are as follows:

  • R-CHOP every 21 d for six cycles with IFRT,  or
  • R-ACVBP (rituximab, doxorubicin, vindesine, cyclophosphamide, bleomycin, prednisolone) and sequential consolidation

For aa-IPI≥2, ESMO notes that no standard of care has been established; enrollment in a clinical trial is preferred. R-CHOP every 21 days for eight cycles is one possible regimen.


A PET-CT scan should be performed to confirm complete remission (CR). Patients in CR should receive clinical follow up with a history and physical examination and laboratory studies (eg, complete blood cell count, comprehensive metabolic panel, lactate dehydrogenase level) every 3-6 months for 5 years and then yearly or as clinically indicated. Imaging studies (CT scan) should be performed no more often than every 6 mo for 2 years after the completion of treatment, and then only as clinically indicated. [73]