Canterbury DHB

Diffuse Large B-Cell Lymphoma (DLBCL)

• This is the commonest type of B cell NHL. 60% are nodal. Of the extra-nodal sites, the GI tract is most common. Blood and bone marrow involvement at diagnosis is rare.
• The cells express CD19, 20, 22, 79a, and sIg in most cases. CD30 is usually negative but can be positive. Cyclin D1 is negative. Ki 67 is usually 50-90%.
• Ig heavy and light chain genes are rearranged. t(14;18), leading to BCL2 gene translocation, occurs in 20-30%; 3q 27 abnormalities occur in 30%. DNA micro arrays have identified subtypes within the DLBCL group, although these no longer predict response to treatment when rituximab is added to CHOP chemotherapy. C MYC may be rearranged in a minority of cases (10-15%).
• Identifying the Cell of Origin (Germinal Centre Cell, Activated B cell) is important for prognosis and is done with immunochemistry. See Hans, C.P., Weisenburger, D.D. (2004). "Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray." Blood 103: 275-82. Patients with activated B cell DLBCL do less well and may benefit from adding other agents. Adding lenalidomide to RCHOP in patients with ABC DLBCL is being tested in the ROBUST study (see clinical trials).
• A further important subgroup of DLBCL are those which have cmyc rearrangement plus bcl2 and/or bcl6 rearrangement (double or triple hit lymphomas). Such lymphomas are often GC cell of origin (see above) and have much poorer outcomes. Those which have overexpression of the products of these genes (double or triple expressors) are commonly of ABC origins, and share characteristics that are similar but not quite so bad. See Swerdlow, S.H., Campo, E. (2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms." Blood 127: 2375-90.

Management

Localised disease (stage I and selected stage II) – Patients with only one lymph node group or two adjacent groups are most commonly treated with 3-4 cycles of immuno-chemotherapy (e.g. R-CHOP) followed by involved field radiotherapy. For selected patients in whom radiotherapy may be problematic (e.g. young woman where the radiotherapy field would involve the breast) a complete course of immuno-chemotherapy (e.g. 6 cycles of R-CHOP) may be preferable. For bulky localised disease, consider a full course of chemotherapy plus radiotherapy.

Poeschel V, Held G, Ziepert M, et al. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet 2020;394(10216):2271-2281. DOI: 10.1016/S0140-6736(19)33008-9.

Advanced disease (stage III and IV) – The current standard of care is 6-8 cycles of R-CHOP with consideration of radiotherapy to sites of original bulky disease at the end of treatment. Modifications may be required for the elderly and patients with cardiac disease (e.g. R-CNOP or R-CEOP). CNS directed therapy is required for at risk patients (risk factors include involvement of testes, epidural space, sinuses, bulk, and high IPI). Patients with Burkitt’s or lymphoblastic lymphoma are treated according to the relevant trial protocols.

Double hit lymphoma – Patients with FISH-demonstrated rearrangements of c-myc and either bcl-2, bcl-6, or both, have a poor outcome with conventional R-CHOP chemotherapy. The current standard of care for fitter patients is the R-DA-EPOCH regimen. See Reagan, P. M. and A. Davies (2017). "Current treatment of double hit and double expressor lymphoma." Hematology Am Soc Hematol Educ Program 2017(1): 295-297.

Further reading

Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. New England Journal of Medicine 2021;384(9):842-858. DOI: 10.1056/nejmra2027612.

Topic Code: 5959