“DLBCL: Understanding the Most Common and Aggressive Neoplasm of the Lymphatic System, Its Uncharacteristic Symptoms, Risk Factors, Diagnostic Process, and Complex Treatment Structure Including CAR-T Cell Therapy for Potential Cure”

2023-04-25 08:30:42

1. DLBCL is the most common neoplasm of the lymphatic system

With around 7 cases per 100,000 inhabitants, diffuse large B-cell lymphoma (DLBCL) is one of the most common malignant neoplasms of the lymphatic system and is the most common subtype of non-Hodgkin lymphoma (NHL). It accounts for approximately 27.9% of all NHLs.¹ Men are affected slightly more often than women¹ and the median age at onset is 70 years². Caucasians get sick more often than Asians or Africans.^1,3

2. The DLBCL is particularly aggressive

DLBCL is a malignant disease of the lymphatic system. Various lymphomas can develop from the B-lymphocytes, which are summarized under the term B-cell lymphoma. It is believed that due to the very rapid rate of division, B lymphocytes are particularly susceptible to replication errors leading to malignant changes. DLBCL is one of the aggressive tumors because the lymphoma cells spread in the early stages of the disease.²

3. Symptoms are uncharacteristic

The first symptoms include rapidly enlarging and swollen lymph nodes, which are not sensitive to pressure and often not sensitive to pain and are therefore usually only discovered at a late stage. If the B-cell lymphoma spreads into the bone marrow, normal blood formation can be inhibited, which manifests itself, for example, in tiredness and exhaustion. However, with the initial diagnosis, this only affects about 10% of patients. As a result of reduced blood platelets (thrombocytopenia), there is an increased tendency to bleed and the lack of white blood cells (leucocytopenia) leads to susceptibility to infections. B symptoms such as fever, night sweats and weight loss, which are common in Hodgkin lymphoma, are rare in DLBCL.^2,4

4. Zunedisabling indications for certain risk factors

There is increasing evidence of the following risk factors: ^2,4

• Contacts with chemical pollutants
• viral (e.g. hepatitis C) and bacterial infections
• Acquired immunodeficiencies e.g. B. by infections with HIV
• Congenital immunodeficiencies
• Age over 60 years

New findings show that long-term stimulation of the immune system by altered substances (auto-antigens) that are therefore recognized as being foreign to the body can promote the development of a lymphoma. The cause of the change in endogenous substances is still largely unexplained.²

5. At dhe diagnostics requires experience

If NHL is suspected, detailed diagnostics are carried out to rule out other diseases and identify the exact subtype for the best possible treatment. A detailed medical history is taken and the symptoms are recorded. A full blood count is taken and, among other things, laboratory tests are carried out to assess liver and kidney values.³ A lymph node biopsy is also performed for histological examination. The examination should be carried out by an experienced hematopathologist, as the diagnosis is often difficult.^2,3 With a confirmed diagnosis of DLBCL, the staging is based on the Ann Arbor classification. The number of affected lymph nodes or extralymphatic involvement, the position in relation to the diaphragm and the presence of B symptoms are taken into account.^3,5

6. The therapy structure is very complex

The standard first-line therapy consists of immunochemotherapy R-CHOP. The anti-CD20 antibody Rituximab (R) is administered in combination with chemotherapy (CHOP = cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/prednisolone).² In the event of a therapy failure in the first line, the therapy is individualized and depends, among other things, on the time of the recurrence, the general condition and, if applicable, the age of the patient. CAR-T cell therapy applies to early recurrences or primarily refractory patients who are capable of high doses according to Oncopedia Guideline and AMWF S3 guideline second line as standard of care.^3,6 This is a novel autologous immunotherapy in which the patient’s own T cells are equipped with a chimeric antigen receptor (CAR) outside the body, which recognizes the antigen CD19, which is common in lymphomas. After a single infusion, these CAR-T cells bind to the target antigens on the tumor cells and kill the tumor cells.^2,7 Autologous stem cell transplantation is recommended for high-dose patients with late recurrences.⁶ In an autologous stem cell transplant, blood stem cells that were previously removed are transplanted back after high-dose chemotherapy. Patients who are not suitable for high-dose therapy are treated with immunochemotherapy, among other things.^3,6 In the case of a recurrence, refractory condition or progression after two lines of therapy, CAR-T cell therapy is also recommended – if the second line of therapy has not yet taken place. ^3,6

7. The DLBCL is in principle curable

If DLBCL is not treated, the disease progresses very quickly and is usually fatal. Fortunately, if the diagnosis is made in good time, the disease can often be treated very well and the patients have a good life expectancy – often with a chance of recovery.⁴

Credentials:

1. Schubert-Fritschle G, Eckel R, Engel J. Epidemiology of malignant lymphoma. In: Dreyling M, Munich T, eds. Malignant lymphomas Recommendations for diagnosis, therapy and aftercare. Zuckerschwerdt; 2019
2. Competence network for malignant lymphomas. Diffuse large B-cell lymphoma. As of December 2021. Retrieved 2023-03-01. https://lymphome.de/diffus-grosszelliges-b-zell-lymphom.
3. German Society for Hematology and Medical Oncology (DGHO). Oncopedia Guidelines – Diffuse large B-cell lymphoma. As of July 2022. Retrieved 2023-03-01. https://www.onkopedia.com/de/onkopedia/guidelines/diffuses-grosszelliges-b-zell-lymphom/@@guideline/html/index.html.
4. Journal Oncology. Diffuse large B-cell lymphoma (DLBCL). As of October 2022. Retrieved 2023-03-01. https://www.journalonko.de/thema/lesen/diffuses_grosszellige_b_zell_lymphom_dlbcl#2Was%20ist%20die%20Ursache%20f%C3%BCr%20ein%20DLBCL%3F.
5. Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol. 1989;7(11):1630-6. doi:10.1200/jco.1989.7.11.1630.
6. Guideline program oncology of the Association of Scientific Medical Societies eV (AWMF), German Cancer Society eV and German Cancer Aid (HRSGS.) S3 guideline diagnostics, therapy and aftercare for adult patients with diffuse large B-cell lymphoma and related entities. Long version 1.0 – October 2022. AWMF registration number: 018/038OL.
7. Mueller AM. CAR T cell therapy. Mechanism of action, indications, products, assessment for clinical practice. In focus: immunotherapies in hemato-oncology. Swiss Z Onkol 2020; 1: 6-10.

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