Diffuse large B-cell lymphoma
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This document provides an overview of diffuse large B-cell lymphoma (DLBCL), including epidemiology, risk factors, presentation, histology, genetics, therapy, and treatment options. DLBCL is the most common subtype of non-Hodgkin lymphoma. The standard first-line treatment is rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). For early stage disease, options include full chemotherapy or abbreviated chemotherapy with radiation. Advanced disease is treated with full chemotherapy. Refractory cases may be treated with newer agents or CAR T-cell therapy.
Diffuse large B-cell lymphoma
- 1. IR ON D EFIC IEN C Y A N D OTH ER H YPOPR OLIFER ATIVE A N EMIA S ZIV H OSPITA L 2 0 2 1 SA MEER SAWA ED , MD
- 2. INTRODUCTION
- 3. EPIDEMIOLOGY • Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of NHL • It is slightly more common in Caucasians and men, and the median age at diagnosis is 64.
- 4. RISK FACTORS The relative risk of DLBCL is higher amongst people with affected first-degree relatives (RR 3.5-fold) patients with congenital or acquired immunodeficiency patients on immunosuppression, and patients with autoimmune disorders also have a higher risk of developing DLBCL, often EBV-related.
- 5. PRESENTATION The majority of patients present with advanced stage disease with only 30–40% of patients having stage I or II disease about 40% of patients will have “B” symptoms 50% of patients will have an elevated LDH. Up to 40% of patients will have involvement of non-lymph node sites including bone marrow, CNS, GI track, thyroid, liver, and skin.
- 6. PRESENTATION Patients with extensive bone marrow involvement, or involvement of the testes, breast, kidney, adrenal gland, paranasal sinus, or epidural space are at increased risk of CNS dissemination.
- 7. HISTOLOGY The tumor consists of a diffuse proliferation of large, atypical lymphocytes with a high proliferative index
- 8. IMMUNE PHENOTYPING These cells typically express the B-cell antigens CD19, CD20, and CD79a. Expression of CD10 and BCL6 is consistent with the tumor cell being of germinal center origin (GCB) while the expression of MUM1 corresponds with the non- GC or activated B cell (ABC) subtype.
- 10. GENETICS BCL2 is overexpressed in anywhere from 25 to 80% of DLBCL, whereas BCL6 is positive in more than two-thirds of cases MYC is rearranged in 10% of DLBCLs, and ~20% of MYC- rearranged cases have concurrent BCL2 or BCL6 rearrangements, a combination referred to as “double-hit lymphoma.” These double-hit lymphomas are associated with an extremely poor prognosis with a median OS of only 12–18 months.
- 13. THERAPY The addition of the anti-CD20 antibody rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improved survival and is the standard first-line chemotherapy for this disease.
- 15. EARLY STAGE DISEASE For patients with early stage disease localized to a radiation field, treatment options include full course chemotherapy with R-CHOP every 3 weeks for 6 cycles/ abbreviated chemotherapy for 3–4 cycles followed by involved field radiotherapy.
- 16. ADVANCED DISEASE For advanced stage DLBCL, therapy is with a full course of chemotherapy.
- 17. OTHER TREATMENT OPTIONS • Several studies have investigated alternative anthracycline-containing chemotherapy regimens and/or consolidation autologous stem cell transplantation in first remission for higher-risk disease without improvement over R-CHOP alone. • Dose adjusted R-EPOCH (rituximab, infusional etoposide/vincristine/ adriamycin, cyclophosphamide, prednisone) is one such regimen.
- 20. R-EPOCH • Although this regimen is no better than R-CHOP for DLBCL in general, it is often used to treat primary mediastinal large B-cell lymphoma and double-hit DLBCL based on results from phase 2 and retrospective studies, respectively.
- 21. CNS PROPHYLAXIS • intrathecal chemotherapy or high-dose systemic methotrexate and leucovorin rescue should be considered for patients with high risk of CNS dissemination. • This includes patients with primary testicular involvement and breast involvement, as well as patients with several IPI risk factors and diffuse bone marrow involvement, renal involvement, or adrenal involvement.
- 22. RESISTANCE • For patients with chemorefractory disease, clinical trials or palliative therapy or clinical trials should be considered, with a goal of achieving a disease response sufficient for allogeneic stem cell transplant.
- 23. OTHER AGENTS FOR REFRACTORY CASES • Several new agents have shown some promise in patients with relapsed DLBCL, including ibrutinib, particularly in the ABC cell of origin subtype, lenalidomide, and everolimus.
- 24. • This strategy uses T cells collected from a patient that are genetically modified to express a receptor that will bind to a surface antigen expressed on the patient’s own tumor cells. • In the case of B-cell malignancies, CD19 has been targeted most commonly. CHIMERIC ANTIGEN RECEPTOR T CELLS (CAR-T CELLS)