Q&A

Dr Mitchell Smith and Dr Julie Dodds tell Pharmafile about recent R&D in the field of blood cancers including follicular lymphoma

Follicular Lymphoma Foundation (FLF): For most patients, follicular lymphoma (FL) is slow developing, which means that it can take a long time for symptoms to appear. Typically, a person presents because of unexplained persistent swelling in the neck, armpit or groin; associated symptoms may be significant weight loss, fevers and drenching night sweats.

The current standard of care can be observation without treatment if there are no symptoms, or, if treatment is indicated, a combination of a chemotherapy drug and a monoclonal antibody.

FLF: FL presents a paradox in that the treatment shrinks the disease in most patients but does not cure it. So, most FL patients have the disease go into remission but then have anxiety waiting for it to return. If the disease comes back within two years, then the outcome is worse.

FLF: The aim of all our research programmes is to accelerate a transformative change in scientific research that will lead to better treatments and cures for FL patients. We are rolling out our first three programmes and are looking forward to reporting on rapid progress. This includes the CURE FL Awards grants programme described in detail below and the Centres of Excellence programme, which will focus on building strategic partnerships with expert academic Institutions that will use innovative approaches to advance knowledge and treatments for FL, aligned with the FLF mission to find a cure – and fast. Finally, our Precision Medicine Programme, which has the goal of improving treatment strategies and speed up the development of new treatments and ultimately a cure for every patient.

FLF: For many people that suffer from FL, there are periods of remission into relapse and back again. Through the CURE FL Awards, we are funding investigation into areas we have identified, through a rigorous review process, as the most promising areas of research in order to understand the biology of FL and find a cure. Each of the new grants is designed to lead to a clinical trial within, or soon after, the two-year grant period. Advances in research give us hope that curative therapies can be developed in the near future. Our goal is to make this happen as soon as possible.

FLF: An extensive review of the FL research landscape identified two areas as the most likely to lead to curative therapies and be available to FL patients as soon as possible:

• Cellular immunotherapy (CAR T and others): Immunotherapy is believed to hold great promise for a curative effect. Immunotherapy treatments take advantage of the body’s natural defences to fight cancer

• Targeted therapies (standalone or in combination with other treatments): Targeted therapies are cancer treatments that use drugs to target specific genes and proteins that are involved in the growth and survival of cancer cells.

These therapies have been the focus of the CURE FL Awards research grants programme.

Cancer cells visible in the bloodstream

FLF: There are multiple unmet needs in FL: First, FL is a highly variable disease. It seems there are a series of genetic steps in the development of FL, and they may be different in different patients. So, we may need to tailor the treatment to the individual patient based on the steps that happened in their FL. To do this, we need to identify biomarkers specific to FL that could be targeted for treatment. Second, FL can change or transform to a fast-growing form, a serious problem, which requires more intense treatment. We need a way to predict when this will happen, both so we can treat it earlier but also if we understood why transformation occurred, we could find better treatments. There are several effective, non-curative treatments for FL, but an unmet need is the ability to select the right treatment at the right time. Of course, new curative treatments are also needed.

FLF: Many years of clinical trials of different chemotherapies failed to show much benefit.

The addition of B-cell-directed monoclonal antibodies, eg, rituximab, were a major advance 25 years ago. Recent findings have generated excitement about immunotherapy, using the T-cells of the immune system to attack lymphoma. The research being funded by CURE FL takes various approaches in search of ways to make immunotherapy work better, perhaps even achieving cures. For patients who relapse early or transform and have worse outcomes despite more treatments, such therapy may be life-saving. For patients with more indolent FL, these treatments may allow them to avoid multiple courses of therapy and cumulative side effects.

FLF: We were attracted by the fact that each project aims to develop a novel or combination involving immunotherapy and targeted therapy, and will also have a clinical trial available or in late-stage planning by the end of the funding period. We hope our leading investigative teams will make strong progress and move quickly towards trials, enabling successful outcomes to be available to patients as soon as possible.

FLF: The cellular immune therapy furthest along in the clinic is chimeric antigen receptor modified T-cells (CAR T). CAR T are a patient’s own T-cells engineered to attack a target, and currently available CAR T attack a protein on all B-cells, including FL. One CURE FL project will design and test CAR T-cells that attack an FL specific pathway they have identified as important for FL survival. Another will develop CAR T that attacks not only B-cells but also the surrounding microenvironment important for FL cell survival. The other two projects examine why some FL cells are not killed by CAR T and look for ways then to make FL cells more sensitive to immune attack.

FLF: There is great excitement about new types of treatments approved since 2020: these include CAR T-cells, antibodies that activate the immune system and molecularly targeted drugs. We need to keep up the momentum, and it takes time, effort and funding to accelerate the pace of discovery and to focus these advances on FL. With the right resources and the right people in our corner, plus the best and most advanced research programmes, we believe we will find a cure – and fast. Our aim is that by the 100th anniversary of the first diagnosis of FL (back in 1925) we will be on the path to a cure – better and less toxic and debilitating treatments, as well as improving the personal journey of every patient.

This article was originally published in Pharmafocus.