New study develops guidelines for treating advanced B-cell lymphoma (ALS)

A team of infectious disease medics from the University Hospital of Reading, in collaboration with scientists from the BRAIN Institute, has developed a new clinical guidance for treating patients with diffuse large B-cell lymphoma (DLBCL) who do not respond to common therapies.

B-cell lymphoma, which occurs in people with certain blood and marrow cell types, are the most common blood cancers found in babies. However, how it arises and how certain immune system cells are activated and suppressed in B-Lymphoma is not well understood.

People with lymphoma rarely respond well to treatment with immune checkpoint inhibitors (ICI) - a commonstay of B-Lymphoma treatment. Like non-IIC-deficient lymphoma, DLBCL does not respond well to ICI and is likely to recur with increasing patient numbers.

The research team found that the use of low intensity immune checkpoint inhibitors ('low-density lipoprotein' or LDL-IP) showed a significant reduction in the frequency of leukocytes activating immune-related leukotrienes in DLBCL cells compared to healthy donor non-IIC lymphomas. Their findings were published today in The EMBO Journal.

This study builds upon prior research findings and clinical trial results to provide evidence-based guidelines for patients with DLBCL who do not respond well to ICI.

"It would be an unwise prescription for doctors to prescribe ICI for patients with DLBCL who do not respond well to ICI, as an almost certain recurrence may follow. In such a case, patients would perhaps also receive unnecessary chemotherapy, typically with anti-PD-1/anti-PD-L1/anti-CL-4 inhibitors. This constitutes a potentially serious side effect," explained Professor Michael Hewson, Head of Fulbright Endowed Professor in Mechanism Research at the University Hospital of Reading.

Highly antigenic and non-specificative lymphoma, and lymphoma with reduced amounts of CD-forming T cells, are the most common forms of DLBCL. In such lymphoma, patients' T cells function by attacking the CD4+ cytotoxic CD8+ T cell, and will rarely fail, especially in patients with large quantifiable lesion numbers.

"There is a clear understanding that the T cells in DLBCL cells are sensitive, which means that while they might be activated, the role of most of the CD8+ T cells in the condition is negligible. However, our finding supports the use of low intensity immune checkpoint inhibitors in lymphomas with a high viral load (LV), in order to reduce the frequency of T cells triggered by ICI and thus protect CD8+ T cells," said Dr. Finnie Mooijders, Associate Professor, Translational Science and Oncology at the University Hospital of Reading and first author of the study.

"The use of immune checkpoint inhibitors meant to give patients 'a quality of life' that would not accompany waiting for current therapies is a great opportunity for an effective therapy for lymphoma. However, it should be observed that it will take at least five years before these treatments can be developed into Phase I systemic clinical trials and what impact they would have in the community since it will depend on patient response," added Professor Michael Hewson, Head of Fulbright Endowed Professor in Mechanism Research.

The group's next steps include exploring the extent to which the use of lipoic acid (a lipopolysaccharide) presnationally activates CD8+ T cells and the extent to which this enhances the leukotriene-stimulated immune memory in subpopulation of Solid tumour reservoirs.