Published: 1st August 2024
In June, our team attended two significant scientific conferences: the European Hematology Association (EHA) conference in Madrid and the Advances in Malignant Lymphoma International Conference in Philadelphia. These events provided the opportunity to foster collaborations with leading researchers and industry partners and learn about the latest advances that are shaping the future of follicular lymphoma (FL) research.
The European Hematology Association (EHA) Conference in Madrid and the Advances in Malignant Lymphoma Conference in Philadelphia both focused on new developments in the treatment of FL and other types of lymphoma. At these conferences, experts shared updates on new treatments like immunotherapies, specifically CAR-T cell therapy and bispecific antibodies, which are showing positive steps forward in treating FL but also require further research to address the challenges. They discussed the importance of making these treatments more accessible and manageable for patients, considering factors like cost, ease of administration, and side effects.
Researchers are also making progress in understanding the genetic factors and cellular processes involved in FL. New studies using advanced techniques are helping scientists identify early warning signs and potential new treatments. Efforts are underway to improve the treatment environment within the body and find ways to overcome resistance to current therapies. Innovations like detailed analysis of genetic information and blood tests to monitor disease are also being developed. These conferences highlighted the ongoing advancements and collaborations aimed at improving treatments and working towards a cure for FL.
Dr Mitchell Smith, CMO, FLF
Highlights from the European Hematology Association (EHA) Conference
The EHA conference is dedicated to promoting excellence in patient care, research, and education in the field of hematology. This year’s event in Madrid, Spain was an excellent opportunity for us expand our collaborations in Europe, spotlight FL, and delve into the future of FL research.
Insights from the Advances in Malignant Lymphoma International Conference
The Fourth AACR International Meeting on Advances in Malignant Lymphoma, held in collaboration with the International Conference on Malignant Lymphoma (ICML) and Blood Cancer Discovery, took place in Philadelphia, US. This conference covered a broad spectrum of lymphoma types, including Hodgkin lymphoma, T-cell lymphomas, and various B-cell lymphomas.
Targeted therapies and immunotherapies
CAR-T and bispecific antibodies remain at the forefront of immunotherapy research, with the latest updates largely reinforcing previously presented data. In addition to trials in relapsed FL, Epcoritamab + R2 first-line treatment, as presented at ICML Lugano 2023, continues to report positive results with extended follow-up.
Impressive talks on new approaches to CAR-T cell therapy included Dr. Josh Brody, an FLF-funded CURE-FL investigator, on how to make CAR-T cells work despite lymphoma immune evasion mechanisms. In addition, Dr. Marco Ruella, who hosts a Mark Foundation-FLF Momentum Fellow in his lab at UPenn, highlighted groundbreaking advancements in this area targeting a specific type of cell.
T-cell engaging therapies have gained approvals based on high response rates in third-line FL, but they also pose risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CAR-T therapy offers a one-time infusion option but there may be barriers to access. Bispecific antibodies require multiple treatments but have developed strategies to mitigate CRS and ICANS.
“We are seeing strong evidence of increasing investment in emerging therapies These therapies will be the future treatments for FL”.
Kate Rogers, CEO, FLF
The National Comprehensive Cancer Network (NCCN), an alliance of leading cancer centers devoted to patient care, research, and education, recognizes these therapies for third line (+) FL, yet long-term data is needed to evaluate their curative potential. Multiple factors influence the decision on a patient’s treatment, such as:
• Treatment access due to approval and reimbursement: Ensuring that the treatment is accessible to patients, which depends on regulatory approval and whether the costs are covered by insurance or other reimbursement methods.
• Dosing regimens, including duration of treatment: Considering the specifics of how often and for how long the treatment needs to be administered.
• Ability to administer in the outpatient setting: Assessing whether the treatment can be conveniently given to patients in an outpatient setting rather than requiring hospitalisation.
• Formulation: The form in which the treatment is provided, such as tablets, injections, or infusions, which can affect ease of use and patient compliance.
• Tolerability of treatments, including long-term toxicity: Evaluating how well patients can tolerate the treatment, with a focus on minimising side effects and long-term toxicities.
Targeted therapies and immunotherapies are also emerging as viable alternatives to traditional chemoimmunotherapy (CIT). Promising fixed-duration, chemo-free bispecific antibody-based combinations in first-line FL so far show promising efficacy and safety. Additionally, studies are being designed to ask whether these new therapies may change the current “watch and wait” approach for patients with low tumor burden. The challenge remains in identifying biological markers for guiding treatment, as current markers to predict early progression of disease (POD) are not clinically very useful.
Advances in genetics and cellular processes
Several laboratories have developed inducible genetic mouse models that mimic FL development, allowing for detailed analysis of the multiple steps involved. These models primarily focus on BCL2 gene, which produces a protein that helps regulate cell death (apoptosis) and plays a key role in FL, as well as several epigenetic genes (KMT2D, CREBBP). These genetic mutations are relevant to patients as they can be detected years before clinical diagnosis of FL and even in otherwise healthy individuals.
Advances in understanding the cycle of normal germinal center B (GCB) cells, the waves of gene expression that are turned off and on during these cycles, and how these processes are perturbed to predispose to and eventually develop into FL are being analysed using increasingly sensitive molecular techniques. These findings relate to FL, originating from GCB cells, and a subset of large B-cell lymphomas sharing GCB origin. Identifying these early cells may define clonal progenitor cells (CPC) as an FL “stem-cell,” a concept pioneered by FLF advisor Prof. Jessica Okosun.
Exploring the lymphoma microenvironment (LME)
Normal GCB cells depend on signals from the LME, especially certain T cells. FL escapes this requirement, and understanding how it does so could lead to new treatments or even preventive measures. Efforts to restore this dependence are underway.
Addressing treatment resistance
Research conducted from the laboratories of FLF-funded CURE-FL investigators Dr Wendel and Dr Beguelin on how FL cells develop resistance to BCL2 inhibitors, BTK inhibitors and CAR-T therapy showcased potential strategies to enhance the effectiveness of these treatments. BTK inhibitors are drugs that block BTK, an enzyme essential for the growth and survival of B-cells, which are involved in FL. By understanding the mechanisms of resistance, the researchers aim to improve the efficacy of these therapeutic approaches.
Technological innovations
Research on multi-omic profiling of the microenvironment in FL and various technologies to assess DNA in blood (“liquid biopsy”) were reviewed by leading researchers in the field. We are optimistic that our successful Biomarker Program grant program will address one or more of these technologies.
Conclusion
These conferences underscored the ongoing advancements in FL research and the importance of integrating new therapies, understanding genetic and cellular mechanisms, and leveraging technological innovations to improve patient outcomes. The future of FL treatment continues to advance, with continued research and collaboration paving the way for better therapies and the search for a cure.
