Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), representing nearly 30% of NHL cases. It is an aggressive cancer of the lymphatic system with the potential to spread to extranodal sites throughout multiple organ systems.1 

The type of treatment for DLBCL depends on whether the disease stage is localized or advanced.2 Treatments include chemotherapy with or without radiation, immunotherapy, and targeted therapy. 

Chemoimmunotherapy for DLBCL

The standard first-line therapy for DLBCL involves multiagent chemotherapy using rituximab and anthracycline derivatives known as R-CHOP, which stands for Rituxan® (rituximab) combined with cyclophosphamide, hydroxydaunorubicin (sold as Lipodox® or Doxil®), Oncovin® (vincristine), and prednisone.2 

This combination chemoimmunotherapy treatment is typically administered in an outpatient setting in a 14- or 21-day cycle with or without subsequent radiation therapy following the completed cycle. For patients with absolute contraindications to anthracyclines, etoposide (sold as Toposar® and Etopophos®) is a viable alternative to hydroxydaunorubicin, forming R-CEOP instead of R-CHOP.2 

In the early stages of DLBCL, 3 to 6 cycles of the 21-day R-CHOP regimen is recommended for patients aged 60 years and under with low-risk DLBCL.3 For advanced-stage DLBCL, R-CHOP is still the recommended treatment, with 6 to 8 cycles using either the 14- or 21-day cycle.

Alternately, for advanced-stage DLBCL, studies have examined the efficacy of variations of the R-CHOP regimen, including a combination of dose-adjusted etoposide, prednisone, Oncovin, cyclophosphamide, and hydroxydaunorubicin with rituximab (DA-EPOCH-R). The EPOCH doses are adjusted to achieve an absolute neutrophil count nadir of 500 cells/µL.4 In one clinical trial, 72 patients with advanced DLBCL (stage II or higher) received 6 to 8 cycles of DA-EPOCH-R, with results showing a 5-year progression-free survival and overall survival of 79% and 80%, respectively.5

Frequent monitoring with a complete blood count, a biochemistry panel, and liver and renal function tests is necessary to assess for chemotoxicity during treatment. Assessment for the potential development of hypersensitivity reactions, tumor lysis syndrome, infections, cystitis, hypotension, bleeding, and toxicities of the gastrointestinal, cardiac, peripheral or central nervous, pulmonary, and integumentary systems must be performed at each clinical visit.6

Research shows that more than half (50% to 70%) of patients with DLBCL who receive R-CHOP treatment can be cured.7,8 

Read more about R-CHOP for DLBCL

Treatment for Refractory or Relapsed DLBCL

Patient response to treatment may depend on DLBCL subtype, so effective first-line treatments may differ according to subtype.9 Patients who are refractory to R-CHOP therapy often exhibit double-hit lymphoma (involving chromosomal translocations of MYC and BCL2 or BCL6), triple-hit lymphoma (involving chromosomal translocations in MYC, BCL2, and BCL6), or double-expression lymphoma (involving high expression of MYC and BCL2).8,9 Poorer prognosis is also associated with the activated B-cell (ABC) molecular subtype of DLBCL compared to that of the germinal center B-cell (GCB) subtype, potentially necessitating chemotherapeutic options other than R-CHOP.9 Additionally, patients with relapsed DLBCL may require treatment with a different chemotherapy regimen.8

For patients with refractory or relapsed DLBCL, second-line chemotherapy treatments may include Xpovio® (selinexor), Monjuvi® (tafasitamab) combined with Revlimid® (lenalidomide), high-dose chemotherapy with autologous stem cell rescue (hematopoietic stem cell transplantation) with or without subsequent radiation, or anti-CD19 chimeric antigen receptor (CAR) T-cell therapy.2

Other salvage regimens for patients with refractory or relapsed DLBCL include8

  • Rituximab plus dexamethasone, cytarabine, and cisplatin (R-DHAP)
  • Rituximab plus ifosfamide, carboplatin, and etoposide (R-ICE)
  • Rituximab plus etoposide, methylprednisolone, cytarabine, and cisplatin (R-ESHAP)
  • Rituximab plus gemcitabine, cisplatin, and methylprednisolone (R-GEM-P)

Read more about DLBCL experimental therapies

Targeted Therapies for DLBCL

Xpovio is a nuclear export inhibitor, which is a type of targeted cancer therapy for DLBCL that inhibits the export of the exportin 1 protein (XPO1) from the nucleus of a lymphoma cell, causing apoptosis.10 Several tumor suppressor genes and proto-oncogenes express the XPO1 protein.11

Another targeted combination therapy is Polivy® (polatuzumab vedotin) with Bendeka® (bendamustine) and rituximab (Pola-BR), an antibody-drug conjugate that specifically targets CD79b using a microtubule inhibitor monomethyl auristatin E (MMAE).11

Several therapies are currently in development that target the CD19 antigen, which is specifically expressed by B cells and involved in B-cell development. These targeted therapies include Monjuvi, Zynlonta® (loncastuximab tesirine), CAR T-cell products such as Breyanzi® (lisocaptagene maraleucel), bispecific T-cell engagers, or a combination of targeted therapies such as Monjuvi and Revlimid. 

Read more about DLBCL therapies


  1. Gandhi S. Diffuse large B-cell lymphoma (DLBCL): practice essentials. Medscape. Updated May 6, 2021. Accessed August 12, 2022.
  2. Gandhi S. Diffuse large B-cell lymphoma (DLBCL) treatment & management: approach considerations. Medscape. Updated May 6, 2021. Accessed August 12, 2022.
  3. Gandhi S. Diffuse large B-cell lymphoma (DLBCL) treatment & management: management of early-stage DLBCL. Medscape. Updated May 6, 2021. Accessed August 12, 2022.
  4. Gandhi S. Diffuse large B-cell lymphoma (DLBCL) treatment & management: treatment of advanced-stage disease. Medscape. Updated May 6, 2021. Accessed August 12, 2022.
  5. Wilson WH, Dunleavy K, Pittaluga S, et al. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008;26(16):2717-2724. doi:10.1200/JCO.2007.13.1391
  6. CHOP+R regimen. Cancer Care Ontario. October 2017. Accessed August 12, 2022.
  7. Goy A. Succeeding in breaking the R-CHOP ceiling in DLBCL: learning from negative trials. J Clin Oncol. 2017;35(31):3519-3522. doi:10.1200/JCO.2017.74.7360
  8. Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure—what to do? Hematology Am Soc Hematol Educ Program. 2016;2016(1):366-378. doi:10.1182/asheducation-2016.1.366
  9. Nowakowski GS, Czuczman MS. ABC, GCB, and double-hit diffuse large B-cell lymphoma: does subtype make a difference in therapy selection? Am Soc Clin Oncol Educ Book. 2015;35:e449-e457. doi:10.14694/EdBook_AM.2015.35.e449
  10. Targeted drug therapy for non-Hodgkin lymphoma. American Cancer Society. Updated April 15, 2022. Accessed August 12, 2022. 
  11. Cheson BD, Nowakowski G, Salles G. Diffuse large B-cell lymphoma: new targets and novel therapies. Blood Cancer J. 2021;11(4):68. doi:10.1038/s41408-021-00456-w

Reviewed by Hasan Avcu, MD, on 10/14/2022.