Diffuse Large B-Cell Lymphoma: Treatment Options

Preparation for Treatment

Prior to treatment, the physician will perform several blood tests to determine if a patient’s organs are healthy and functioning sufficiently to withstand the effects of treatment. These tests can include a complete blood count, liver and kidney function tests, and a lactate dehydrogenase test, which is a general indicator of tissue damage.


Standard Treatment Options

Beginning in the 1970s, DLBCL was treated with a combination of chemotherapy medications known as CHOP, which stands for cyclophosphamide (Cytoxan), doxorubicin (also called hydroxydaunomycin; Adriamycin), vincristine (Oncovin), and prednisone. In the early 2000s, the monoclonal antibody rituximab (Rituxan) was found to significantly improve outcomes when added to this regimen. As such, the most widely used treatment for DLBCL presently is the combination known as R-CHOP. The R-CHOP regimen is usually given in 21-day cycles (once every 21 days) for an average of 6 cycles. However, the length and number of cycles given can vary based on the patient’s individual disease and health status. In certain cases 14-day cycles may be used, and for limited stage disease (Stage I or II) 3-4 cycles may be used followed by radiation therapy. 

Sometimes an additional chemotherapy drug, etoposide (Vepesid, Toposar, Etopophos), is added to the R-CHOP regimen, resulting in a drug combination called R-CHOEP. A related regimen, called R-EPOCH, involves the same drugs administered as a continuous infusion over 4 days. There are some cases in which R-EPOCH may be the preferred regimen, as in HIV-related DLBCL. While there are differences in toxicity between these regimens, there are no studies to suggest one is significantly better than another. Randomized clinical studies are currently underway comparing the effectiveness of R-CHOP to R-EPOCH in various groups of patients with DLBCL. 

DLBCL typically requires immediate treatment, because it is an aggressive (fast-growing) lymphoma. The standard frontline treatment of R-CHOP can be given with or without radiation therapy, and it can lead to disease remission (does not return after treatment) in a large number of patients with DLBCL. However, for some patients, the disease does return. For patients in whom the disease has relapsed (returns after responding to treatment) or for those whose disease is refractory (does not respond to treatment), other therapies may be successful. 

High-dose chemotherapy followed by stem cell transplantation can be used to treat patients with DLBCL whose disease is refractory or relapsed following initial chemotherapy. The majority of patients undergoing stem cell transplantation will have an autologous transplant (patient receives his or her own stem cells, collected prior to the procedure). Occasionally, a patient will undergo an allogeneic transplant (patient receives stem cells from a donor). For more information on stem cell transplantation, pre-order the Lymphoma Research Foundation publication titled Understanding the Stem Cell Transplantation Process on the Lymphoma Research Foundation’s (LRF’s) website at www.lymphoma.org/publications

For those relapsed/refractory patients who are not stem cell transplant candidates or who choose not to have a stem cell transplant, other combination chemotherapy regimens are available. These second-line regimens include: 

  • ifosfamide, carboplatin, and etoposide (ICE) 
  • dexamethasone, cisplatin, and cytarabine (DHAP) 
  • gemcitabine-based therapy 
  • single-agent rituximab 
  • bendamustine (Treanda) plus rituximab 
  • lenalidomide (Revlimid) plus rituximab 

Other drugs and combination therapies are under research. 


Customized Treatment Based on DLBCL Subtype 

A great deal of current research in the field of DLBCL is focused on using precision medicine to select customized treatments based on a patient’s DLBCL subtype. For example, ibrutinib (Imbruvica), a targeted therapy that is FDA approved for use in several other types of lymphoma, has been studied for use in DLBCL to see if it affects the subtypes differently. In a recent phase II clinical trial of patients with relapsed or refractory disease, the ABC subtype of DLBCL was shown to be much more responsive to ibrutinib than the GCB subtype. This is of particular importance considering that the ABC subtype is more likely to respond poorly to standard R-CHOP treatment. Based on this study’s results, an international phase III trial is now underway comparing standard chemotherapy with or without ibrutinib in patients with non-GCB subtypes of DLBCL.

A similar line of research is exploring the addition of lenalidomide to R-CHOP chemotherapy. The data to date seem to show that this regimen may also work better in the ABC subtype of DLBCL. Doctors are hopeful that this research into adding ibrutinib, lenalidomide, and other agents to the R-CHOP or R-EPOCH regimens will lead to targeted treatments and better outcomes for patients with ABC and the other non-GCB DLBCL subtypes.