Indolent follicular lymphoma: what is the right time to initiate therapy?

Question

Accepted Answer

A 49-year-old patient was first diagnosed with so-called indolent (i.e. slowly progressing) follicular lymphoma. To make sure that the diagnosis was correct and to find out whether treatment should be started immediately despite the non-aggressive nature of the disease, she sought advice from a German hematology expert. The shared records included a medical history, blood test and lymph node tissue histology and immunohistochemistry results, as well as a PET-CT scan.

Problem statement

Were the available studies sufficient to confirm the diagnosis and should the treatment be started urgently?

Selected format

Written consultation

Outcome

The case was referred to Professor Thomas Elter, a hematologist at the Center for Integrative Oncology at the University of Cologne. The physician first recommended that the biopsy material be sent for histological re-evaluation and additional molecular genetic analysis by specialized laboratory at the Cologne University Hospital. He also considered it advisable to have the imaging studies re-evaluated by the University Hospital radiologists.

Slide revision confirmed the diagnosis of follicular lymphoma, and the results of fluorescence in situ hybridization (FISH) performed as part of the molecular genetic analysis for translocation of BCL2, BCL6, and MYC genes were negative, which made it possible to define the grade of lymphoma as 1-2. Such lymphomas are classified as indolent tumors because of their nonaggressive, slow progressing course.

Review of PET/CT images showed multiple lymph node involvement both above and below the diaphragm, with the largest lymph node 3 cv in diameter.

Taking into account all the data, the professor gave a favorable prognosis for the course of the disease. He noted that the condition was considered incurable, but its presence did not affect the average life expectancy. The acute phase of the disease ran in waves, which means that the size of individual lymph nodes could both increase and decrease. Referring to studies conducted at the Mayo Clinic (USA), Prof. Elter reported that antibodies contained in green tea extract or camel milk in a large number of cases had led to a decrease in the size of the affected lymph nodes. It is not necessary to take such a high dose as was used in the study (4000 mg), but a gentle dose of 1000-1500 mg per day can be started, which does not affect the quality of life.

With regard to antitumor drugs, the specialist emphasized that with each relapse of the disease, the remission period was shortened due to the development of cell resistance to chemotherapy (on average 5 years after the first chemotherapy, 2-3 years after the second and 1 year after the third). Therefore, the standard recommendation was to delay therapy initiation for as long as possible. Lymph node sizes up to 10 cm were not considered critical and did not require treatment just because of how large they were. The size of each individual lymph node was taken into account and the total size of the conglomerates was of secondary importance. Chemotherapy should only be started if the disease started to have a negative impact on the quality of life, including, for example, changes in appearance.

Prof. Elter was reassuring: with modern monoclonal antibody drugs combined with immunotherapy (obinutuzumab in combination with bendamustine), more than half of all patients were still in remission five years after the first therapy, with the highest probability of relapse in the first 2 years. In this case, modern therapies (e.g. CAR-T) could increase survival from 10% to 80%.

Medconsonline comment

The patient was undoubtedly correct in her decision to seek a second opinion when a malignant disease of the lymphatic system was detected. In such conditions, the accuracy and completeness of the lymphoma tissue laboratory examination is of great importance for making the correct diagnosis, so a review of its results with expansion of its scope was quite justified. The same applies to the results of imaging studies. Based on the findings which he could fully trust, Prof. Elter could be quite confident in his conclusions about the nature of the disease, and come up with precise recommendations as to its optimal treatment tactics based on current international clinical guidelines.

Нematology