Lymphoma Research Foundation awards $5.7m to pursue blood cancer treatments

The Lymphoma Research Foundation—a nonprofit dedicated to funding innovations in lymphoma research—has announced 29 research grants for 2022, totaling more than $5.7m USD in support for scientists working to treat and cure various subtypes of the blood cancer.

To learn more about the program and the important work of this year’s slate of grant winners, Outsourcing-Pharma connected with Sonali Smith, chair of the Lymphoma Research Foundation’s scientific advisory board, and two of the 2022 recipients.

OSP: Could you please share the ‘elevator presentation’ description of the LRF—history, key achievements, and some of the key ways in which you support advancement in lymphoma treatments/diagnostics.​

SS: With a mission to eradicate lymphoma and serve those touched by this disease, the Lymphoma Research Foundation (LRF) is a leader in funding innovative lymphoma research and supporting the lymphoma community through evidence-based education programs, resources, and support services. Through lymphoma-specific research grants and consortia, LRF seeks to better understand the more than 100 subtypes of lymphoma and support the development of new treatments.

LRF’s focus on supporting early-career scientists ensures the best and brightest remain in the field of lymphoma research so that innovation and progress continue. Simultaneously, LRF works tirelessly to help patients, survivors’ caregivers, and families understand their diagnosis and ensure they have access to the support and resources they need.

OSP: Then, please share your perspective on how treatments/diagnostics for lymphoma have progressed in recent years—struggles, bright spots, promising candidates and approved therapies, etc.​

SS: I entered this field more than twenty years ago, and what has transpired in the past few decades is absolutely remarkable. We have seen advances on nearly all fronts, from improved diagnostics, classification, targeted treatment, and survival. Perhaps one of the most fundamental, yet exciting, advances is in better understanding of how complex lymphomas can be at a biologic level, and how that translates into different patient outcomes. Some important examples are the identification of “double hit” lymphomas and biologic subsets of CLL (i.e. 17p deleted/TP53 mutated).

In terms of diagnostics, we have seen PET scans completely change the ability to predict outcomes, as they offer a more precise means of determining remission. In Hodgkin lymphoma, PET scans have directed the reduction in treatment intensity. Treatment options for all lymphomas have exploded, and we have gone from intensive combination chemotherapy to monoclonal antibodies, immunotherapy, immunomodulatory agents, oral targeted agents, and most recently, to cellular therapy and bispecific antibodies. The overall impact is improved survival and quality of life.

On the horizon, we have exciting research on liquid biopsies, improved immunotherapy, the incorporation of artificial intelligence/machine learning, and much more. There are so many “walking miracles” that would not have survived during the time I was undergoing training, and today are either cured or living with their lymphoma with an excellent quality of life.

OSP: Please tell us about your grant program—why you decided to establish it, and the types of grantees you tend to award your grants to.​

SS: The Lymphoma Research Foundation (LRF) is committed to funding the most promising lymphoma researchers and advancing the understanding of the more than 100 different subtypes of lymphoma.  LRF’s disease-specificity and hyper-focus on finding cures for every type of lymphoma ensure the next generation of cancer researchers dedicate their careers to studying lymphoma, and world-leading lymphoma experts collaborate and accelerate the pace of scientific discovery.

Since its inception, LRF has made major contributions to the lymphoma research enterprise, awarding more than 475 research grants totaling more than $72 million. The Foundation’s volunteer Scientific Advisory Board (SAB), comprised of 45 world-renowned lymphoma experts, guides the Foundation’s research activities, seeking out the most innovative and promising lymphoma research projects for support.

LRF supports innovative research through its Young Investigator Grants Program, which seeks to provide early-career scientists with opportunities for independent research and mentoring, and its Disease Focus Area Grants, which support faculty researchers studying specific subtypes and/or patient populations through a variety of funding mechanisms.

OSP: Please share what makes these specific grantees worth the LRF grant honor:​

• Clarissa Corinaldesi, Columbia University
• Juan Alderuccio, Miller School of Medicine of the University of Miami

SS: Dr. Corinaldesi’s project is focused on adolescents and young adults with a rare but aggressive subtype of lymphoma called Burkitt lymphoma. While aggressive chemotherapy can cure many patients, there are some patients where the initial treatment does not work, and there are very limited opportunities to salvage the disease.

Her goal is to evaluate biologic differences between “curable” and “not curable” disease by using sophisticated genetic studies. While the project focuses on Burkitt lymphoma, her insight is highly likely to inform other lymphoma subtypes as well. The LRF grant will support her efforts to understand the critical biologic differences so that we can tailor treatment and improve outcomes.

Dr. Alderuccio’s project is very timely and capitalizes on a new area of therapeutic agents for the most common indolent lymphoma, follicular lymphoma. Follicular lymphoma can be very challenging to treat, partly because patients live for a very long time but are subjected to repeated courses of treatment and risk for transformation to a more aggressive disease. This project will investigate an exciting new antibody-drug conjugate, loncastuximab teserine, along with rituximab in order to develop a targeted regimen that will hopefully be less toxic than many other available therapies.  

OSP: Do you have any other news or programs you’d like to share from the LRF?​

SS: The Lymphoma Research Foundation (LRF) seeks to eradicate this disease by supporting innovative research and the development of new and improved treatments for lymphoma. Direct investment in cutting-edge science is the primary way LRF advances its mission. Facilitating collaboration and partnerships among academic scientists, clinicians, government, and regulatory agencies, and patients is also a critical component of this work.

Through its global lymphoma consortia, research initiatives, and scientific workshops, LRF mobilizes the research community to overcome systemic challenges and speed up the progress of new treatment development.

OSP: Do you have anything to add?​

SS: These are very exciting times for lymphoma research. The refinement of immunotherapy, both in terms of cellular therapy (i.e. CAR-T) and bispecific antibodies, will continue to revolutionize our treatment options. There is also a focus on quality of life and on limiting the intensity of treatment. Already, there are some mature lymphoid cancers where chemotherapy is being slowly eliminated, such as chronic lymphocytic leukemia. Similarly, some of the most toxic chemotherapies are being replaced by more targeted agents, such as the elimination of bleomycin for the majority of patients with classical Hodgkin lymphoma. Onwards!

Juan Alderuccio, Miller School of Medicine, University of Miami​

OSP: Tell us a little bit about your work in research, and how you came to focus on lymphoma (and FL in particular).​

JA: During my internal medicine residency, I had the opportunity to treat many patients with hematological malignancies. During these years, I became fascinated by the complexity of lymphoma biology and advances in target and immunotherapies. Once I started my Hematology & Oncology fellowship in the care of lymphoma patients is when I chose to pursue a career in lymphoma research. The Lymphoma Research Foundation will help establish my career as an independent lymphoma clinical investigator in experimental therapeutics integrating molecular imaging in the risk stratification of lymphoma patients with the goal of developing biomarker-driven clinical trials. 

Early in my fellowship, I decided to pursue a career in lymphoma working under the mentorship of Dr. Izidore Lossos. I had the opportunity to manage patients with several types of lymphoma treated with standard and experimental therapies. Working with him for several years provided me with a unique perspective on lymphoma biology and therapy and helped me to foster my research skills. Most recently, Dr. Craig Moskowitz joined the Sylvester Comprehensive Cancer Center leadership, and we developed studies testing PET/CT-based biomarkers and clinical trials in aggressive and indolent lymphomas. I am extremely lucky to have such wonderful mentors supporting my career.

OSP: Could you tell us a little bit about the work you’ll be using the grant funding to support? [note: please envision you’re talking to, say, a smart relative—someone who’s not a medical expert like you but who might enjoy a relatively solid grasp of such concepts]​

JA: Follicular lymphoma (FL) represents the most common indolent lymphoid malignancy in the United States. Loncastuximab tesirine is an antibody-drug conjugate directed against CD19. In this study, we propose to test the efficacy of loncastuximab tesirine in combination with rituximab to achieve complete metabolic response by week 12 of treatment in patients with relapsed/refractory (r/r) Follicular Lymphoma.

The proposed study will establish an innovative clinical trial implementing dual-antibody targeted treatment in relapsed/refractory Follicular Lymphoma. The proposed novel combination might significantly improve the complete response rate and prolong survival. Positive results will provide preliminary data to warrant further clinical investigation of loncastuximab tesirine in FL and will inform the design of a randomized multicenter clinical trial.

We hope this study will lead to the development of highly effective and safer therapy in FL. This study will also provide preliminary information on a non-invasive predictive model incorporating metabolic tumor volume, radiomics, machine learning, and clinical data to better identify which patients will benefit the most from antiCD19-directed therapy. Imaging can provide a more comprehensive view of whole-body tumor phenotypic heterogeneity in its entirety via PET/CT data and may develop better risk stratification. Moreover, machine learning may streamline volume calculations for an earlier transition to clinical studies.

OSP: Then, please share your hopes/expectations of how your work will progress, and what’s next if things go how you hope with loncastuximab tesirine.​

JA: My career goal is to develop an innovative academic career as a clinical investigator and leader in the field of lymphoma. I have a primary interest to integrate PET/CT-based data in predictive models for treatment selection coupled with drug development in lymphoma.

In 10 years from now, I hope to have contributed to the development of broadly available, effective, and tolerable therapies for lymphoma patients. Furthermore, being an LRF grantee will support my progress as an independent clinical investigator and receive mentorship from leaders in the field.

OSP: Do you have anything to add?​

JA: Upon completion of my postgraduate medical training in Argentina, I decided to move to the United States aiming to pursue a career in clinical research and drug development in oncology. This decision entailed starting all over again in medical training with associated personal and professional challenges. Despite some initial struggles, I had the opportunity to learn from outstanding mentors that clearly nourish my career as a clinical investigator in lymphoma.

Clarissa Corinaldesi, Columbia University​

OSP: Please tell us a little bit about your work in research, and how you came to focus on lymphoma (and therapy-refractory Burkitt in particular).​

CC: I was trained as a human biologist with a focus on immunology. I have been always fascinated by the Janus-faced role of the immune system cells and their potential impact on a good or bad prognosis during infections or malignant transformation. When I had the opportunity to join the group of Riccardo Dalla-Favera, a giant in the study of B cell lymphomas, I decided that was an excellent opportunity to grow as a scientist and to address questions that were of interest to me.

Understanding the pathogenesis of cancer, including lymphoma, is very challenging and intriguing from a scientific point of view. Trying to solve this biological complicated puzzle triggered and reinforced my commitment to research.

The Lymphoma Research Foundation (LRF) funded project is on a rare lymphoma that typically develops in children and young adults. I always thought that the well-being of children and young people determines our future as humans.  Even if most pediatric patients can survive, they may experience long-term unfavorable side effects from the aggressive treatments they are going through. Our research is focused on understanding the fundamental mechanisms and the biological features of bad prognosis Burkitt lymphoma patients and it should lead toward the development of more effective and safer treatments for these patients.

OSP: Could you tell us a little bit about the work you’ll be using the grant funding to support?​

CC: The Lymphoma Research Foundation (LRF) funded project is focused on identifying biological markers for Burkitt lymphoma (BL) patients who do not respond to therapy or relapse. BL is a rare, but highly aggressive lymphoma, mostly affecting children. Most of these patients are effectively cured with aggressive chemotherapeutic treatment, but some of them show resistance and incurable relapses. The biological features distinguishing the patients who do not respond to therapy are largely unknown. The overall goal of this project is to identify genetic and transcriptomic differences between curable and refractory BL.

OSP: Then, please share your hopes/expectations of how your work will progress, and what’s next if things go well—i.e. once you’ve identified the pathways/targets/etc., how will that important information be put to use?​

CC: Understanding the biological differences beyond the diverse BL responses to current therapy will pave the road toward the identification of effective targeted therapies. Lymphomas are heterogeneous tumors and there are no risk factors that have been specifically identified to prevent them. However, the exceptional progress in targeted therapy and immunotherapy gives me hope for the future. In particular, CAR T-cell therapies seem to be very promising.

Personally, The LRF fellowship will give me the opportunity to acquire more knowledge and to improve my skills. In addition, it will help me to grow as a scientist toward a career as an independent investigator.

OSP: Do you have anything to add?​

CC: Research is never-ending, there is always something new to discover and understand. The fact that there is always a new problem/scientific puzzle to solve, triggers my commitment to finding explanations.

I would like to thank the generous Lymphoma Research Foundation donors who give me the opportunity to reach my professional and educational goals. Together we work to improve the lives of blood cancer patients and eventually find the best cure for all of them.