Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), and unlike the indolent forms it is curable with the right treatment: more than 60% of cases are curable overall. It is an aggressive lymphoma, and it is divided into gene-expression subtypes and variants that differ in prognosis and in how they are treated.
Who gets it and how it presents
DLBCL makes up to 33% of all new cases of NHL in the United States, and the median age at diagnosis is about 60–70 years. Factors associated with its development are immune deficiency and immune suppression, infection with HIV or Epstein-Barr virus (EBV), rheumatoid arthritis (RA), older age and male sex.
Most patients are already in an advanced stage when they are diagnosed, and only 30% are still in an early stage. Patients usually present with B symptoms (night sweats, fever and unintentional weight loss) together with a high lactate dehydrogenase (LDH), and these features are mostly related to the advanced stage at which DLBCL is found. In 20–30% of cases there is extranodal involvement, meaning disease outside the lymph nodes, most often of the ovary, testis, central nervous system (CNS), bone and kidney.
Subtypes: ABC and GCB
Gene-expression profiling divides DLBCL into two subtypes that differ in prognosis:
- ABC (activated B-cell-like) — has a poorer prognosis than GCB, is characterised by activation of the NF-κB pathway, and often expresses markers such as MUM1 (multiple myeloma 1).
- GCB (germinal centre B-cell-like) — has a generally better prognosis and expresses markers such as CD10 and BCL6.
Variants
Beyond the two gene-expression subtypes, DLBCL includes several variants.
The main variant is primary mediastinal B-cell lymphoma (PMBCL), the most common variant that arises in the thymus, for which the main treatment strategy is the standard regimen R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone).
The other group is the highly proliferative variants, which are intermediate between Burkitt lymphoma and DLBCL and carry a worse prognosis. They include:
- double-hit lymphoma, which carries both a MYC abnormality and a BCL2 or BCL6 abnormality;
- triple-hit lymphoma, which carries all three of BCL2, BCL6 and MYC;
- MYC-positive lymphoma;
- DLBCL in which more than 90% of the cells are Ki-67 positive (Ki-67 is a marker of dividing cells).
Because these variants divide so rapidly, their treatment is better done with intensive or palliative regimens such as R-EPOCH and IVAC-R.
Salvage therapy
Salvage therapy is the treatment given when the first-line regimen has failed, and it should be started only when there is histological proof of relapse, or of not having reached a complete remission. When the disease recurs, the treatment of choice is an autologous haematopoietic stem cell transplant (HSCT), in which the patient’s own stem cells are used to rescue the marrow after high-dose chemotherapy. The common salvage regimens are R-ICE and R-DHAP, and other options are bendamustine, an alkylating chemotherapy agent, and CAR-T cell therapy.