new research lymphoma

• Recent findings and future directions in non-Hodgkin's lymphoma therapy

July 01, 2021

Complex, multifaceted therapy is the name of the game in non-Hodgkin's lymphoma treatment, according to research by Stephen M. Ansell, M.D., PhD. , a hematologic oncologist at Mayo Clinic's campus in Rochester, Minnesota. This and other findings were published in February 2021 in the Journal of Clinical Oncology (JCO).

Dr. Ansell had hoped that immune checkpoint blockade might combat immune dysfunction in non-Hodgkin's lymphomas as effectively as in Hodgkin's lymphoma. However, that didn't prove to be the case.

Previously, Dr. Ansell and colleagues discovered in a clinical trial of nivolumab that immune checkpoint blockade is a safe and effective therapy for refractory Hodgkin's lymphoma. The New England Journal of Medicine published their results in 2015.

Dr. Ansell explains that for non-Hodgkin's lymphoma, it was curious to him and others studying tumor microenvironment (TME) that the T cells were not effectively targeting the cancer. What they have discovered is that continuous activation has worn out these cells, exhausting and suppressing them and hindering their readiness to attack tumors.

Therefore, with the exception of a few patient subsets, immune checkpoint blockade alone has proven ineffective as a single therapy for non-Hodgkin's lymphomas. From this study, Dr. Ansell determined the following:

• The immune system needs more support to activate and prevent suppression, targeting tumor cells rather than aiding the development of malignancy.
• A combination approach is necessary to mount a sufficient response to these lymphomas: immune checkpoint blockade plus chemotherapy, or other immune-active agents.

"I think we're coming to realize that one thing alone is not the answer for non-Hodgkin's lymphomas," says Dr. Ansell. "An integrated approach of bringing multiple components together and changing various facets of the immune system is really where we're trying to get to — to create a whole new reprogrammed tumor environment."

Specifically, according to the paper in JCO , an effective non-Hodgkin's lymphoma therapy needs to address these obstacles:

• Inadequate presentation of tumor-associated antigens
• Immunosuppressive cells in the TME
• Cancerous cells overexpressing immunosuppressive ligands
• Cytokine secretion leading to immune exhaustion or immune activation suppression

Background for the JCO findings

Dr. Ansell's lymphoma research program, which focuses on the TME and B cell cancer biology, has produced over 450 journal articles, including the 2021 paper in JCO . A fellowship at Mayo Clinic piqued his interest in this line of research, and during that period, he became interested in lymphoma — particularly lymphoma biology — while working in a B cell malignancy lab. His focus during the fellowship — and since then — has been the TME .

He explains that initially the lymphoma program's research focused on one or two immune checkpoint therapies, but now multiple possibilities have arisen with these therapies. An area of new research that he considers exciting is one that not only exploits the adaptive immune system — the T cell side — but also targets the malignant cells with the innate immune system, the macrophages and monocytes, or the so-called trash collectors of the immune system.

While investigators have made great strides in the last 10 years in treating B-cell lymphomas, progress with T-cell lymphoma has been more modest, according to Dr. Ansell.

Considerations for physicians on reaching a precise diagnosis

As there are numerous non-Hodgkin's lymphoma subtypes, experts may disagree about a precise diagnosis. Dr. Ansell indicates that an adequate biopsy is a crucial component in identifying the exact type of non-Hodgkin's lymphoma.

In addition, expertise in recognizing the various subtypes is critical to an accurate diagnosis, he says. He recommends a second opinion on pathology and also referring a patient to a medical center such as Mayo Clinic with broad experience in distinguishing non-Hodgkin's lymphomas.

Future perspectives on lymphoma research and treatment

Dr. Ansell is positive about the future of non-Hodgkin's lymphoma research and treatment.

"In lymphoma treatment and research, this is a remarkable time with an almost overwhelming amount of riches as regards available novel treatment approaches," says Dr. Ansell. "Twenty years ago, we focused entirely on the tumor cell. But now we understand we can change the environment in which these tumor cells are growing and get the immune system to engage with the tumor in a far greater way. I think the big advance we are likely to see in the future is taking multiple agents that are really promising and utilizing them in combination."

He says patient outcomes now far exceed what they were 10 years ago. "There's a wave of immunotherapies happening across cancer, in part driven by some of the work done here at Mayo Clinic," he says. "So what's really exciting now is to see the biology coming full circle to impact patients and seeing great clinical success, particularly for patients with lymphoma."

Dr. Ansell considers the treatment horizon for lymphoma very promising with novel treatments, novel combinations and the use of these agents in combination with standard treatments to profoundly change patient outcomes.

For more information

Ansell SM. Checkpoint blockade in lymphoma. Journal of Clinical Oncology. 2021;5:525.

Ansell SM, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. The New England Journal of Medicine. 2015;372:311.

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Trial of cell-based therapy for high-risk lymphoma leads to FDA breakthrough designation

In an early Stanford Medicine study, CAR-T cell therapy helps some with intractable lymphoma, but those who relapse have few options. Modifying the therapy’s molecular target improved response.

July 9, 2024 - By Krista Conger

T cell attacking a cancer cell. Meletios Verras/Shutterstock.com 

CAR-T cell therapy, which targets a specific protein on the surface of cancer cells, causes tumors to shrink or disappear in about half of patients with large B-cell lymphoma who haven’t experienced improvement with chemotherapy treatments.

But if this CAR-T treatment fails, or the cancer returns yet again — as happens in approximately half of people — the prognosis is dire. The median survival time after relapse is about six months.

Now, a phase 1 clinical trial at Stanford Medicine has found that a new CAR-T cell therapy that targets a different protein on the surface of the cancer cells significantly improved these patients’ outcomes: Over half of 38 people enrolled in the trial — 37 of whom had already relapsed from the original CAR-T therapy — experienced a complete response of their cancers. More than half of all treated patients lived at least two years after treatment.

“On average, the patients enrolled in this trial had received four previous lines of therapy,” said assistant professor of medicine and the trial’s principal investigator Matthew Frank , MD, PhD. “These patients are out of likely curative options, and they are scared. Half of them will die within five to six months. But in this trial, we saw a very high rate of durable complete responses, meaning their cancers became undetectable.”

‘Breakthrough therapy’

The original CAR-T therapy, approved by the Food and Drug Administration in 2017, involves removing immune cells from the patient and inserting a gene to help the cells attack a protein called CD19 on the surface of the lymphoma cells. The new version of the therapy instead targets a molecule called CD22.

In September 2022, the FDA designated CD22-targeting CAR-T therapy for large B-cell lymphoma a Breakthrough Therapy, a move that is meant to speed the development and review of particularly promising drugs that may provide a substantial improvement over existing therapies for serious conditions. 

The study was devised and conducted entirely at Stanford Medicine.

“This trial was an example of what it means to take an idea from preclinical studies in animals all the way into the patient at an academic medical center,” said David Miklos , MD, PhD, professor of medicine and chief of blood and marrow transplantation and cellular therapy. “Remarkably, the FDA — after reviewing our preliminary data — contacted us to urge us to apply for breakthrough therapy designation, rather than waiting for us to approach them. This will help us significantly as we move into larger clinical trials.”

A larger, phase 2 trial led by Frank is now ongoing at multiple sites around the country.

Miklos is the senior author of the study , which was published July 9 in The Lancet . Frank; assistant professor of medicine John Baird, MD; and postdoctoral scholar Anne Kramer , MD, PhD, are the lead authors of the research.

CAR-T cell therapy was first approved by the FDA as a treatment for relapsed or treatment-resistant diffuse large B-cell lymphoma and for children and young adults under 25 with acute lymphoblastic leukemia.

Matthew Frank

Six CAR-T cell therapies are now approved for several types of lymphoma, multiple myeloma and acute lymphoblastic leukemia. Four of these therapies target CD19, which is found on the surface of healthy and cancerous B cells; two target another protein on the cells’ surface called B cell maturation agent.

CD22 is another protein found on the surface of mature B cells, and researchers have been eying it for some time as a possible second target for CAR-T cell therapy. That’s because, although CAR-T cell therapy targeting CD19 is typically successful, many patients relapse quickly as the cancer cells figure out how to reduce the amounts of CD19 on their surfaces or their engineered immune cells become exhausted from a prolonged attack.

Several trials have experimented with engineering CAR-T cells that recognize both CD19 and CD22 — exploring whether a double volley of attack might eliminate cancer cells before they learn how to evade the treatment.

These efforts have met with mixed success. While more people with acute lymphoblastic leukemia responded to the double-targeted CAR-T therapy, the results for people with lymphoma were more tempered. In a trial conducted at Stanford Medicine, the therapy had some efficacy but was no more effective than targeting CD19 alone. Frank, Miklos and their colleagues wondered what would happen if only CD22 were targeted.

A new target

The researchers collected immune cells called T cells from 38 patients with large B-cell lymphoma whose cancers had started growing after previous therapies including chemotherapy. All but one of the patients had also progressed after CAR-T therapy targeting CD19; the cancer cells of the one remaining patient did not express CD19 on their surfaces.

The T cells were grown and genetically engineered to target CD22 in Stanford Medicine’s Laboratory for Cell and Gene Medicine in partnership with the Center for Cancer Cell Therapy. They were then infused back into the patients from whom they were derived.

Of the 38 patients, 68% saw their cancers shrink, and 53% achieved a complete response, meaning their cancers were no longer detectable.

David Miklos

“This is not just a high response rate, but many of these remissions have been quite durable over a median of 30 months of follow-up,” Frank said. “If this holds true in larger trials, it will surpass other therapeutic option we have for these patients.” Additionally, most patients experienced minimal, manageable side effects.

The results of the trial are the first in a series of hurdles CD22-targeted CAR-T cell therapy will have to clear for it to be approved by the FDA for routine clinical use for those with intractable large B-cell lymphoma. According to Miklos, it also highlights the advantages of intertwining medicine and research.

“We conducted the preclinical studies at Stanford Medicine, translated the findings in our cell manufacturing and cancer cell therapy centers, and cared for the patients here,” said Miklos, who is a member of the Stanford Cancer Institute . “This pipeline allows us to leverage our research and clinical findings in an iterative way. If something is not working, we can refocus and retool our approach to pivot quickly to new approaches to help our patients.”

“It is rare for an academic medical center to attain a breakthrough designation,” Frank noted. “It’s humbling. Larger trials need to be completed, and FDA approval is not guaranteed, but this is a huge achievement for all the members of the team and a hopeful sign for patients and their caregivers.”

Researchers from Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan and Cancer Center Amsterdam, who are currently working at Stanford, contributed to the work.

The study was funded by the National Institutes of Health (grants 2P01CA049605-29A1, 5P30CA124435 and K08CA248968), the Virginia and D.K. Ludwig Fund for Cancer Research, the Parker Institute for Cancer Immunotherapy, the European Hematology Association, the Lymph&Co Foundation, and the Leukemia and Lymphoma Society.

Miklos has consulted for Kite Pharma-Gilead, Juno Therapeutics-Celgene, Novartis, Janssen and Pharmacyclics. Research support from Kite Pharma-Gilead, Allogene, CARGOTherapeutics, Pharmacyclics, Miltenyi Biotec and Adaptive Biotechnologies.

Frank has consulted for Kite Pharma-Gilead, Adaptative Biotechnologies and CARGO Therapeutics; he has also received research support from Kite-Pharma-Gilead, AllogeneTherapeutics, Cargo Therapeutics and Adaptative Biotechnologies.

Study co-author Crystal Mackall, MD, the Earnest and Amelia Gallo Family Professor and professor of pediatrics and of medicine, is a founder of CARGO Therapeutics and holds equity in and consults for the company. CARGO holds the license for the CD22-directed CAR-T cell therapy.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

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Fighting lymphoma: Treatment options include alternatives to chemotherapy

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By Sharon Theimer

Chemotherapy is usually the first treatment doctors try to treat  lymphoma , including the two most common forms:  non-Hodgkin  and  Hodgkin . But alternatives to chemotherapy are developing, as first-line treatments and as backup options, explains  Stephen Ansell, M.D., Ph.D. , hematology chair and hematologic oncologist at the  Mayo Clinic Comprehensive Cancer Center .

Lymphoma is a type of blood cancer that begins when a germ-fighting white blood cell, called a lymphocyte, mutates and rapidly multiplies. There were roughly a half-million new cases of non-Hodgkin lymphoma and 82,409 new cases of Hodgkin lymphoma in 2022, making them the 10 th  and 26 th  most commonly diagnosed cancers that year, respectively, according to the most recent statistics from the World Health Organization's  International Agency for Research on Cancer . 

Symptoms may include swollen lymph nodes, itchy skin, night sweats, fever, persistent fatigue, unexplained weight loss and shortness of breath.

Developing new therapies to improve lymphoma outcomes for people with lymphoma is a high priority for Dr. Ansell.

"It's about improving outcomes while minimizing side effects — using treatments that can specifically target the cancer and have less of an impact on the body's healthy, normal cells," Dr. Ansell says. "There is a high percentage of patients whose lymphoma is cured. When people are cured, they may have to deal with long-term complications. Our idea is to have the best outcomes and minimize long-term problems."

Dr. Ansell's studies have included work as part of Mayo's Early Cancer Therapeutics Group. The therapeutics research group offers patients whose cancers haven't responded to chemotherapy the opportunity to join early phase clinical trials of potential new treatments.

People with lymphoma may receive chemotherapy alone or a combination of chemotherapy and nonchemotherapy treatments, Dr. Ansell says. Nonchemotherapy options include immunotherapy, chimeric antigen receptor-T cell therapy (CAR-T cell therapy), targeted therapy, bone marrow transplant and radiation therapy, he explains:

• Immunotherapy  uses the body's immune system to fight cancer, blocking cancer cells' ability to hide from the body's attempts to attack it. There are several types of immunotherapy. Dr. Ansell's research contributed to the treatment of lymphoma with immune checkpoint therapy, drugs that help the immune system fight cancer cells without destroying healthy cells.
• In  CAR-T cell therapy , some of a patient's white blood cells, including T cells, are removed and treated in the lab to produce chimeric antigen receptors, or CARs, that activate T cells' ability to recognize and kill cancer cells. The CAR-T cells are then infused back into the patient. This form of immunotherapy is considered one of the most promising areas of cancer treatment. Dr. Ansell is a member of the CAR-T Cell Therapy Program at Mayo Clinic.
• Targeted therapy  uses drugs or other substances — alone or in combination — to identify and attack abnormalities within cancer cells with less harm to normal cells. Dr. Ansell is currently researching potential new drug combinations and their side effects.
• A  bone marrow transplant , also known as a stem cell transplant, infuses healthy blood-forming stem cells into the body to replace bone marrow that's not producing enough healthy blood cells.
• Radiation therapy  uses high-powered energy beams, such as X-rays and protons, to kill cancer cells. For certain types of non-Hodgkin lymphoma, radiation therapy may be the only treatment you need, particularly if your lymphoma is slow growing and located in just one or two spots. More commonly, radiation is used after chemotherapy to kill any lymphoma cells that might remain.

Unfortunately, there is no known way to prevent lymphoma, but a healthy diet and exercise are important. They can help people with lymphoma better cope with cancer treatments and have better outcomes, Dr. Ansell says.

Learn more about lymphoma and find a clinical trial at Mayo Clinic.

Join the Blood Cancers and Disorders Support Group on Mayo Clinic Connect , an online community moderated by Mayo Clinic for patients and caregivers.

Also, read these articles:

• CAR-T cell therapy helps man continue community advocacy
• How precise diagnosis of lymphoma offers patients best treatment options
• CAR-T cell researchers at Mayo Clinic optimistic about future of treating blood cancers
• All-Star pitcher Liam Hendriks shares how he closed out cancer

A version of this article was originally published on the Mayo Clinic News Network .

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New Treatment Results for Follicular Lymphoma Clinical Trial Presented at ASH 2023

By Julie Grisham Monday, December 11, 2023

A clinical trial helped Anne Schmiedel (shown here with her husband, Bob) avoid chemotherapy while still successfully treating her follicular lymphoma.

Thanks to a clinical trial (research study) of a targeted immunotherapy drug called mosunetuzumab (Lunsumio™), Anne Schmiedel is now in remission from follicular lymphoma .

“These days I feel really good,” Anne says. “My energy levels are good, and I’m able to do everything I want to do. I’m thankful like you can’t even believe.”

Nearly all the patients in that phase 2 trial experienced some tumor shrinkage, and three-quarters now have no evidence of disease.

These early but promising results were reported by Memorial Sloan Kettering Cancer Center (MSK) lymphoma specialist Lorenzo Falchi, MD , at the 2023 American Society of Hematology (ASH) Annual Meeting.

“We have been waiting for a drug that could replace chemotherapy in these patients,” Dr. Falchi says. “Although we need to follow the patients for a longer period of time, this treatment may be what we’ve been looking for.”

Mosunetuzumab for Follicular Lymphoma: Clinical Trial Results

The trial enrolled people with a type of non-Hodgkin lymphoma called follicular lymphoma that was severe enough to require treatment and who had not previously received any treatment for their cancer. Follicular lymphoma is the most common type of low-grade lymphoma .

Mosunetuzumab was offered to patients instead of standard therapy — which is a combination of chemotherapy and immunotherapy . This approach allowed the participants to avoid common side effects of traditional chemotherapy.

The analysis is based on the first 45 patients to participate in the study:

• 96% had at least some shrinkage of their follicular lymphoma tumors.
• 76% had a complete response, meaning no evidence of disease remained.

How Does Mosunetuzumab Shrink Lymphoma Tumors?

The drug that Anne received, mosunetuzumab, is a bispecific antibody. This novel class of drugs consists of two parts: One part recognizes a marker on the patient’s immune T cells, and the other part recognizes a marker on the patient’s cancerous B cells. The drug acts like a lasso bringing the two cell types together, which allows the patient’s own immune system to destroy the lymphoma.

The Inspiration for Studying Mosunetuzumab for Follicular Lymphoma

“Mosunetuzumab is already approved for treating people with lymphoma whose disease does not respond to standard treatments,” Dr. Falchi says. “Studies have shown that in 80% of those patients, their tumors were partially reduced, and in 60%, the tumors were completely gone.” In these earlier studies, the drug kept the cancer under control for an average of two years.

“We have been waiting for a drug that could replace chemotherapy in these patients,” says Dr. Lorenzo Falchi. “Although we need to follow the patients for a longer period of time, this treatment may be what we’ve been looking for.” 

Dr. Falchi and his colleagues had a hunch: If mosunetuzumab worked in patients who hadn’t received any previous treatment, perhaps they could avoid chemotherapy altogether.

“Chemotherapy has a number of side effects, including a risk of additional cancers,” Dr. Falchi says. “In addition, between 15% and 20% of patients do not adequately respond to it.”

Relief Seeing Cancer Disappear From Scans, Thanks to MSK Clinical Trial 

This image shows PET scans of Anne Schmiedel’s torso before and after treatment. On the left, lymph nodes throughout her body show high levels of metabolic activity, which indicates the presence of active cancer. After treatment, on the right, the lymph nodes no longer show activity because the cancer has been put into remission. 

Anne received 10 doses of mosunetuzumab, which is given every three weeks as an injection in the belly, starting in March 2023. When she had her first scan less than three months after beginning the treatments, she was astonished: The cancer was going into remission.

“I still remember the day I saw those scans,” Anne says. “And then in September 2023, I was told I’d had a complete response. It doesn’t get any better than hearing those words.”

About half of people in the mosunetuzumab trial experienced a side effect called cytokine release syndrome (CRS), which can cause fevers, dizziness, and body aches, among other symptoms. It’s a common side effect of drugs that activate the immune system, like mosunetuzumab. Anne experienced CRS just once, after her first dose. Later, a subsequent dose had to be delayed due to low blood counts, but overall, she felt well throughout her treatment.

Anne’s Follicular Lymphoma Treatment at MSK

Anne was first diagnosed in the fall of 2019, after an MRI she received in preparation for spine surgery revealed enlarged lymph nodes in her abdomen, a common symptom of follicular lymphoma. She immediately went to MSK, where she was cared for by lymphoma specialist Paul Hamlin, MD , a co-author of the study presented at ASH.

Dr. Hamlin told her that even though she had cancer, she didn’t need treatment right away. So Anne had the spine surgery, which was successful. Dr. Hamlin and his team continued to monitor her lymphoma regularly with scans and blood tests. This approach is called active surveillance.

About three years later, in the summer of 2022, blood work revealed that Anne had become severely anemic, another symptom of follicular lymphoma. After tests ruled out other possible causes of the anemia, Anne got the news she was hoping not to hear: It was time to begin treatment.

Deciding To Participate in an MSK Clinical Trial and Avoid Chemotherapy

Thankfully, Dr. Hamlin also had some good news. There was a trial that would allow her to avoid chemotherapy.

“I knew there would be risks to participating in a trial, but Dr. Hamlin thought that someone in my situation could really benefit,” Anne says. She remembers that during discussions about what to do, someone in her family said, “MSK is on the cutting edge of everything. If you have the opportunity to receive the latest treatment, why wouldn’t you go that route?”

Anne received most of her treatments at the David H. Koch Center for Cancer Care at MSK in Manhattan, but she has been able to go for some of her blood work and scans at MSK Westchester , closer to her home.

“There’s no way I would have gone anywhere else but MSK,” says Anne, now 70.

Dr. Falchi plans to continue studying the effectiveness of mosunetuzumab for patients who have not yet received other treatments.

The mosunetuzumab study was sponsored by Genentech.

Dr. Falchi’s research receives essential philanthropic support from the MSK Giving community, including the Lymphoma Research Foundation and the Steven A. Greenberg Charitable Trust. 

Dr. Falchi discloses relationships with and/or financial interests in the following companies through professional services and activities: ADC Therapeutics, AbbVie, AstraZeneca, Evolveimmune, GenMab, Genentech, Innate, Intellisphere, Ipsen Pharmaceuticals, Physicians’ Education Resource, Projects In Knowledge, Seagen, and the Taylor & Francis Group.

Dr. Hamlin discloses relationships with and/or financial interests in Calithera through professional services and activities.  

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FDA Approves New Treatment For Adults With Relapsed Or Refractory Large-B-Cell Lymphoma

FDA News Release

Today, the U.S. Food and Drug Administration approved Breyanzi (lisocabtagene maraleucel), a cell-based gene therapy to treat adult patients with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least two other types of systemic treatment. Breyanzi, a chimeric antigen receptor (CAR) T cell therapy, is the third gene therapy approved by the FDA for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

“Today’s approval represents another milestone in the rapidly progressing field of gene therapy by providing an additional treatment option for adults with certain types of cancer affecting the blood, bone marrow, and lymph nodes,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Gene and cell therapies have evolved from promising concepts to practical cancer treatment regimens.”

DLBCL is the most common type of non-Hodgkin lymphoma in adults. Non-Hodgkin lymphomas are cancers that begin in certain cells of the immune system and can be either fast-growing (aggressive) or slow-growing. Approximately 77,000 new cases of non-Hodgkin lymphoma are diagnosed in the U.S. each year and DLBCL represents approximately one in three newly diagnosed cases.

Each dose of Breyanzi is a customized treatment created using a patient’s own T-cells, a type of white blood cell, to help fight the lymphoma. The patient’s T-cells are collected and genetically modified to include a new gene that facilitates targeting and killing of the lymphoma cells. Once the cells are modified, they are infused back into the patient.

The safety and efficacy of Breyanzi were established in a multicenter clinical trial of more than 250 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%.

Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities. Both CRS and neurological events can be life-threatening. Other side effects include hypersensitivity reactions, serious infections, low blood cell counts and a weakened immune system. Side effects generally appear within the first one to two weeks following treatment, but some side effects may occur later.

Because of the risk of CRS and neurologic toxicities, Breyanzi is being approved with a risk evaluation and mitigation strategy (REMS) which includes elements to assure safe use (ETASU). The FDA is requiring, among other things, that healthcare facilities that dispense Breyanzi be specially certified. As part of that certification, staff involved in the prescribing, dispensing or administering of Breyanzi are required to be trained to recognize and manage the risks of CRS and neurologic toxicities. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi.

To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Breyanzi.

The FDA granted Breyanzi Orphan Drug , Regenerative Medicine Advanced Therapy (RMAT) and Breakthrough Therapy designations. The RMAT designation program was created under the 21st Century Cures Act to help facilitate the expeditious development of regenerative medicine therapies intended for serious conditions. Breyanzi is the first regenerative medicine therapy with RMAT designation to be licensed by the FDA. Orphan Drug designation provides incentives to assist and encourage the development of drugs for rare diseases. The Breyanzi application was reviewed using a coordinated, cross-agency approach, including both the Center for Biologics Evaluation and Research and FDA’s Oncology Center of Excellence.

The FDA granted approval of Breyanzi to Juno Therapeutics Inc., a Bristol-Myers Squibb Company.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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Study shows new treatment for lymphoma doesn't require chemo

By Mallika Marshall, MD

June 20, 2024 / 6:09 PM EDT / CBS Boston

BOSTON -- Researchers at the National Institutes of Health found a new treatment for lymphoma that is not chemotherapy. 

The recent study focused on a non-chemotherapy treatment for people with aggressive B-cell lymphoma that has come back or is no longer responding to standard treatments. 

In a clinical trial involving 50 patients, the combination of five drugs shrank tumors substantially in more than half -- in about a third of patients, the tumors disappeared entirely. At two years, a third of the patients were still free of disease.

Researchers hope adding other drugs to the mix can provide even better outcomes for patients.

• Cancer Research
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Mallika Marshall, MD is an Emmy-award-winning journalist and physician who has served as the HealthWatch Reporter for CBS Boston/WBZ-TV for over 20 years. A practicing physician Board Certified in both Internal Medicine and Pediatrics, Dr. Marshall serves on staff at Harvard Medical School and practices at Massachusetts General Hospital at the MGH Chelsea Urgent Care and the MGH Revere Health Center, where she is currently working on the frontlines caring for patients with COVID-19. She is also a host and contributing editor for Harvard Health Publications (HHP), the publishing division of Harvard Medical School.

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NIH Grant Will Support Lymphoma Research

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With new NIH funding, Weill Cornell Medicine investigators will explore how alterations to the packaging of DNA that affect gene expression, known as epigenetic changes, influence the trajectory of diffuse large B-cell lymphomas. Credit: Shutterstock

Weill Cornell Medicine has received a five-year, $12.4 million grant from the National Cancer Institute, part of the National Institutes of Health, for an extensive program of basic and translational research on the biology of diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma.

The investigator-initiated Program Project grant, led by Dr. Leandro Cerchietti , the Richard A. Stratton Associate Professor in Hematology and Oncology at Weill Cornell Medicine, and Dr. Christopher Flowers , professor and chair of the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center , is meant to support a collaborative, multi-faceted effort towards a major biomedical research goal. 

Dr. Leandro Cerchietti

DLBCL represents a significant challenge for cancer biologists because about 40% of patients either don’t respond well to initial chemotherapy or end up relapsing. Response rates also can vary dramatically among different DLBCL subtypes. Researchers expect that the development of significantly better treatments will require a more comprehensive understanding of the complex processes that trigger and sustain the disease.

DLBCL cells are known to originate from antibody-producing B cells residing in lymph node structures called germinal centers. As part of the normal immune response, for example to fight infection, B cells gather in these centers, briefly proliferating and mutating their antibody-coding genes to diversify their ability to bind to antigens. This ultimately allows the antibody response to effectively neutralize its targets. But B cells in this high-mutation state are especially vulnerable to cancerous changes. The collective work of lymphoma scientists has shown in prior studies that lymphoma-driving gene mutations often work by reprogramming B cells so that they linger in germinal centers, eventually accumulating full malignancy.

As part of the newly funded research program, the researchers intend to reveal this lymphomagenesis process in unprecedented detail, showing how different combinations of gene mutations and interactions with partner immune cells can combine to turn germinal center B cells into different DLBCL subtypes. They will focus strongly on the role of chromatin—the overall packaging of DNA, which programs gene activity and gives cells their basic identity—as the key integrator and modulator of these interactions in germinal center B and DLBCL cells.

The laboratories of Drs. Ari Melnick , Steven Josefowicz , Ethel Cesarman , Giorgio Inghirami , Sanjay Patel , John Leonard and Christopher Mason at Weill Cornell Medicine will collaborate on the various projects funded by the grant. These investigators, as well as Dr. Cerchietti, are members of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. Dr. Michael Green , an associate professor in the Division of Cancer Medicine at MD Anderson, will contribute his laboratory’s expertise to the projects as well.

The researchers expect their progress in understanding DLBCL origins to illuminate vulnerabilities in these cancers that can be exploited with new and precise treatments—with emphasis on milder, non-chemotherapy treatments that will be more tolerable, especially for older patients. For example, Dr. Cerchietti and colleagues aim to develop methods for reprogramming lymph node-resident T cells so that they attack DLBCL cells.

Dr. Cerchietti noted that he and his colleagues will be able to make use of the unique collections of patient tumor samples and novel preclinical models of lymphoma that have been developed over years of collaboration by the investigators participating in this grant under the scientific umbrella of the Weill Cornell Medicine Lymphoma Program , as well as from the MD Anderson team. 

“This generous grant will allow us to make real advances in understanding lymphoma biology, but it is built on substantial foundations we’ve laid in recent years with our collaborative basic and preclinical research, as well as clinical trials,” Dr. Cerchietti said.

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Discovery suggests new way to target mantle cell lymphoma

By jim schnabel weill cornell medicine.

A form of blood cancer known as mantle cell lymphoma is critically dependent on a protein that coordinates gene expression, such that blocking its activity with an experimental drug dramatically slows the growth of this lymphoma in preclinical tests, according to a study from Weill Cornell Medicine researchers.

The discovery , reported Oct. 25 in the Journal of Clinical Investigation, could lead to new mantle cell lymphoma drugs as well as a better understanding of how this type of lymphoma develops.

“There’s a strong need for better therapies against mantle cell lymphoma, and our findings suggest that inhibition of this protein, called FOXO1, could be an effective new strategy to try alone or in combination with existing drugs,” said co-senior author Jihye Paik, associate professor of pathology and laboratory medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

Lymphomas are cancers that arise in lymph nodes, small organs where immune cells gather to intercept infectious pathogens. Mantle cell lymphomas (MCLs) arise from immune cells called B cells, which make antibodies, in areas of lymph nodes known as “mantle zones.” Most cases are diagnosed in men who are in their 60s or 70s. MCL is relatively rare, with only about 2,000 new cases per year in the United States, and it often progresses slowly, but it generally recurs after therapy and is considered virtually incurable.

In the study, the researchers used CRISPR/Cas9 gene-editing technology on arrays of MCL cells grown in the laboratory to block 1,427 different transcription factor proteins. Transcription factors are proteins that bind to DNA and work as master programmers of gene activity. Many cancers depend on the activities of particular transcription factors, although traditionally they have been hard to target with drugs.

The screening process revealed several transcription factors whose disruption caused a severe slowdown in MCL cell division, without slowing the growth of other cell types. The researchers discovered in further experiments that one of these, FOX01, is responsible for driving the activities of the others – and essentially works as a critical factor sustaining the pattern of gene activity that defines MCL cells.

Paik and Dr. Hongwu Zheng, the other co-senior author of the study and an assistant professor of research in pathology and laboratory medicine at Weill Cornell Medicine, soon got in touch with scientists at a biotechnology company, Forkhead Biotherapeutics. The company has been trying to develop FOX01-inhibiting compounds for possible use in treating type 1 diabetes. Using an experimental FOX01 inhibitor from the company, the researchers found that it had similar effects on MCL cells as blocking FOX01 by genetic means. The compound also significantly extended survival in a mouse model of MCL.

FOX01 is critical for the development of some normal cell types. Prior studies also have found evidence that FOX01 helps to suppress, rather than promote, some other cancers. Yet in this study, adult mice tolerated a month of FOX01-inhibitor treatment with no major side effects.

“This has the potential to be a relatively safe strategy for treating MCL,” Zheng said.

The researchers plan to continue their preclinical investigations by further optimizing FOXO1 inhibitors and looking for a suitable combination with other drugs for more potent and durable responses.

Jim Schnabel is a freelance writer for Weill Cornell Medicine.

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NIH Grant Will Support Lymphoma Research

Weill Cornell Medicine has received a five-year, $12.4 million grant from the National Cancer Institute, part of the National Institutes of Health, for an extensive program of basic and translational research on the biology of diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma.

The investigator-initiated Program Project grant, led by Dr. Leandro Cerchietti , the Richard A. Stratton Associate Professor in Hematology and Oncology at Weill Cornell Medicine, and Dr. Christopher Flowers , professor and chair of the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center , is meant to support a collaborative, multi-faceted effort towards a major biomedical research goal. 

Dr. Leandro Cerchietti

DLBCL represents a significant challenge for cancer biologists because about 40% of patients either don’t respond well to initial chemotherapy or end up relapsing. Response rates also can vary dramatically among different DLBCL subtypes. Researchers expect that the development of significantly better treatments will require a more comprehensive understanding of the complex processes that trigger and sustain the disease.

DLBCL cells are known to originate from antibody-producing B cells residing in lymph node structures called germinal centers. As part of the normal immune response, for example to fight infection, B cells gather in these centers, briefly proliferating and mutating their antibody-coding genes to diversify their ability to bind to antigens. This ultimately allows the antibody response to effectively neutralize its targets. But B cells in this high-mutation state are especially vulnerable to cancerous changes. The collective work of lymphoma scientists has shown in prior studies that lymphoma-driving gene mutations often work by reprogramming B cells so that they linger in germinal centers, eventually accumulating full malignancy.

As part of the newly funded research program, the researchers intend to reveal this lymphomagenesis process in unprecedented detail, showing how different combinations of gene mutations and interactions with partner immune cells can combine to turn germinal center B cells into different DLBCL subtypes. They will focus strongly on the role of chromatin—the overall packaging of DNA, which programs gene activity and gives cells their basic identity—as the key integrator and modulator of these interactions in germinal center B and DLBCL cells.

The laboratories of Drs. Ari Melnick , Steven Josefowicz , Ethel Cesarman , Giorgio Inghirami , Sanjay Patel , John Leonard and Christopher Mason at Weill Cornell Medicine will collaborate on the various projects funded by the grant. These investigators, as well as Dr. Cerchietti, are members of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. Dr. Michael Green , an associate professor in the Division of Cancer Medicine at MD Anderson, will contribute his laboratory’s expertise to the projects as well.

The researchers expect their progress in understanding DLBCL origins to illuminate vulnerabilities in these cancers that can be exploited with new and precise treatments—with emphasis on milder, non-chemotherapy treatments that will be more tolerable, especially for older patients. For example, Dr. Cerchietti and colleagues aim to develop methods for reprogramming lymph node-resident T cells so that they attack DLBCL cells.

Dr. Cerchietti noted that he and his colleagues will be able to make use of the unique collections of patient tumor samples and novel preclinical models of lymphoma that have been developed over years of collaboration by the investigators participating in this grant under the scientific umbrella of the Weill Cornell Medicine Lymphoma Program , as well as from the MD Anderson team. 

“This generous grant will allow us to make real advances in understanding lymphoma biology, but it is built on substantial foundations we’ve laid in recent years with our collaborative basic and preclinical research, as well as clinical trials,” Dr. Cerchietti said.

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Hodgkin Lymphoma

• What Is Hodgkin Lymphoma?
• Key Statistics for Hodgkin Lymphoma
• What’s New in Hodgkin Lymphoma Research and Treatment?
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• Treating Classic Hodgkin Lymphoma, by Stage
• Treating Nodular Lymphocyte-predominant Hodgkin Lymphoma
• Treating Hodgkin Lymphoma in Children
• Hodgkin Lymphoma Treatment During Pregnancy
• Living as a Hodgkin Lymphoma Survivor
• Second Cancers After Hodgkin Lymphoma
• Late and Long-term Side Effects of Hodgkin Lymphoma Treatment
• If You Have Hodgkin Lymphoma

What's New In Hodgkin Lymphoma Research?

Imaging tests.

Treatments used today cure about 8 out of 10 cases of Hodgkin lymphoma (HL). Still, important research is going on in many university hospitals, medical centers, and other institutions around the world. Scientists are getting closer to finding out what causes the disease and how to better treat it. This is of special interest for hard-to-treat cases, like those that don't respond to current treatments or come back after treatment. Doctors are also looking for ways to limit the long-term side effects linked to HL treatment.

PET/CT scans are commonly used to help doctors stage HL and decide how much treatment needs to be given. Doctors are also looking at whether PET/CT scans done during treatment can help decide if more or less treatment is needed.

Researchers are trying to find out if MRI scans might work as well in children and teens with HL. If so, it would mean less radiation exposure and the resulting long-term side effects in young people.

Overall cure rates for HL are high, but long-term side effects of treatment are an important issue. A very active area of research is directed at learning which patients can be treated with gentler therapy and which patients need stronger treatment.

Doctors are looking to see which patients (especially children) might do just as well with lower doses of radiation, or even no radiation . They're also studying if newer forms of radiation therapy , such as intensity-modulated radiation therapy (IMRT) and proton therapy, might be useful for HL. These approaches focus radiation more precisely on tumors, which limits the doses reaching nearby normal tissues.

Chemotherapy

A related area of research is finding less-toxic treatments that have fewer serious long-term side effects, yet still cure as many patients as possible. Lower doses of chemotherapy (chemo), as well as new chemo drugs and drug combinations are being studied. Many of these drugs are already used to treat other cancers and have shown promise against HL that has come back (relapsed) after other chemo treatments. Studies are in progress to see if these drugs could work better than the ones now in use.

Doctors are also looking for better chemo drugs to use with stem cell transplant. Again, improving outcomes while limiting long-term side effects is the goal.

Another approach is using newer drugs that better target HL cells. Some of these are described below.

Targeted therapy

Newer drugs that work differently from standard chemo drugs are now being studied. Researchers are learning a lot about the gene changes found in HL cells. This could lead to drugs that target these changes and spare normal cells. These are known as targeted therapy drugs. Many other types of cancer are already treated with targeted therapies.

Some of these targeted drugs are being studied in combinations, in the hope that they might work better when given together. Many are given along with other cancer treatments, like chemo and/or radiation. 

Immunotherapy (including monoclonal antibodies)

Immunotherapy is treatment that helps the body’s immune system find and attack cancer cells. Immunotherapy is helpful against several types of cancer, including Hodgkin lymphoma.

Immune checkpoint inhibitors

Immune system cells normally have substances on them that act as checkpoints to keep them from attacking healthy cells in the body. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Today, drugs that block these checkpoints are used to treat HL after other treatments have been tried. Researchers are now studying other ways to use these drugs. For instance, they're looking at whether these drugs might be used as "maintenance therapy" to keep HL from coming back after transplant. They're also testing them as a first treatment for HL. The use of immune checkpoint inhibitors in children and teens, as well as in older people who are too sick to get standard treatment, is also being studied. Several other checkpoint inhibitor drugs are being studied, too.

Chimeric antigen receptor (CAR) T-cell therapy

In this treatment, immune cells called T cells are removed from the patient’s blood and altered in the lab so they have receptors called chimeric antigen receptors , or CARs on their surface. These receptors can attach to proteins on the surface of lymphoma cells. The altered T cells are then multiplied in the lab and put back into the patient’s blood. They can then find the lymphoma cells and launch a precise immune attack against them.

This technique has shown encouraging results in early clinical trials against some hard-to-treat Hodgkin lymphomas. Doctors are still improving how they make the T cells and are learning the best ways to use them. CAR T-cell therapy is only available in clinical trials at this time.

Monoclonal antibodies

Monoclonal antibodies (mAbs) are man-made versions of immune system proteins. Some can kill cancer cells by themselves. Others have radioactive molecules or cell poisons attached to them, which help kill cancer cells. An advantage of these drugs is that they seem to target lymphoma cells while having fewer side effects than standard chemo drugs. They may be used alone or along with chemo.

Some mAbs, such as brentuximab vedotin (Adcetris) and rituximab (Rituxan), are already being used to treat some cases of HL. Researchers are now studying if these drugs might be useful in other ways. For instance, brentuximab is now being studied to see if it might be helpful earlier in the course of the disease or as part of the treatment used to get ready for a transplant. And studies are now being done to see if rituximab can help treat classic forms of HL as well as the nodular lymphocyte-predominant type. Researchers are also looking for the best way to use mAbs along with standard treatment. Many newer mAbs are now being studied, too.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.

Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med . 2015;372:311-319.

Mata E, Díaz-López A, Martín-Moreno AM, et al. Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets. Oncotarget . 2017;8(67):111386-111395.  

Nieto Y, Thall PF, Ma J, et al. Phase II Trial of High-Dose Gemcitabine/Busulfan/Melphalan with Autologous Stem-Cell Transplantation for Primary Refractory or Poor-Risk Relapsed Hodgkin's Lymphoma. Biol Blood Marrow Transplant . 2018 Mar 1.

Regacini R, Puchnick A, Luisi FAV, Lederman HM. Can diffusion-weighted whole-body MRI replace contrast-enhanced CT for initial staging of Hodgkin lymphoma in children and adolescents? Pediatr Radiol . 2018 Jan 23.  

Watkins MP, Fanale MA, Bartlett NL. SOHO State of the Art Updates and Next Questions: Hodgkin Lymphoma. Clin Lymphoma Myeloma Leuk . 2018;18(2):81-90.

Last Revised: May 1, 2018

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy .

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Galapagos announces FDA clearance of IND application for Phase 1/2 ATALANTA-1 study of CD19 CAR-T, GLPG5101, in relapsed/refractory non-Hodgkin lymphoma

Mechelen, Belgium; August 23, 2024, 07:00 CET; regulated information – inside information – Galapagos NV (Euronext & NASDAQ: GLPG) today announced that the U.S. Food and Drug Administration (FDA) has cleared Galapagos’ Investigational New Drug (IND) application for ATALANTA-1, a Phase 1/2 multicenter study evaluating the feasibility, safety, and efficacy of GLPG5101 in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL).

GLPG5101 is an autologous CD19 CAR-T cell therapy product candidate produced using Galapagos’ innovative decentralized cell therapy manufacturing platform with the potential for the administration of fresh, fit cells within a median vein-to-vein time of seven days.

The primary objective of the Phase 1 part of ATALANTA-1 is to evaluate the safety and preliminary efficacy of GLPG5101 to determine the recommended dose for Phase 2. Secondary objectives include assessment of efficacy and feasibility of decentralized manufacturing of GLPG5101. The primary objective of the Phase 2 study is to evaluate the objective response rate. The secondary objectives include complete response rate, duration of response, progression free survival, overall survival, safety, pharmacokinetic profile, and the feasibility of decentralized manufacturing. Each enrolled patient will be followed for 24 months.

The Phase 1/2 ATALANTA-1 study is currently ongoing in Europe, and early data have shown encouraging results in patients with R/R NHL. 1

“We are dedicated to accelerating breakthrough innovation that extends the reach of cell therapies to patients with rapidly progressing cancers,” said Dr. Paul Stoffels 2 , Galapagos’ CEO and Chairman of the Board of Directors. “Our innovative, decentralized manufacturing platform is designed to overcome many of the challenges faced by existing CAR-T production methods. The Galapagos platform has the potential for greater speed and scalability, with the delivery of fresh, fit cells with a median vein-to-vein time of seven days, close to patients. The IND clearance for the Phase 1/2 study of GLPG5101 marks a significant milestone in our cell therapy clinical program, bringing us one step closer to offering our CD19 CAR-T cell therapy to patients in the U.S.”

About non-Hodgkin lymphoma and GLPG5101 GLPG5101 is a second generation anti-CD19/4-1BB CAR-T product candidate, administered as a single fixed intravenous dose. It is currently being assessed in the ATALANTA-1 Phase 1/2, open-label, multicenter study to evaluate the safety, efficacy and feasibility of decentralized manufactured GLPG5101 in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). Non-Hodgkin lymphoma is a cancer originating from lymphocytes, a type of white blood cell which is part of the body’s immune system. Non-Hodgkin lymphoma can occur at any age although it is more common in adults over 50 years old. Initial symptoms usually are enlarged lymph nodes, fever, and weight loss. There are many different types of non-Hodgkin lymphoma. These types can be divided into aggressive (fast-growing) and indolent (slow growing) types, and they can be formed from either B lymphocytes (B cells) or in lesser extent from T lymphocytes (T cells) or Natural Killer cells (NK cells). B-cell lymphoma makes up about 85% of non-Hodgkin lymphomas diagnosed in the US. Prognosis and treatment of non-Hodgkin lymphoma depend on the stage and type of disease.

About Galapagos’ cell therapy manufacturing platform Galapagos’ innovative, decentralized cell therapy manufacturing platform has the potential for the administration of fresh, fit cells within a median vein-to-vein time of seven days, greater physician control and improved patient experience. The platform consists of an end-to-end xCellit® workflow management and monitoring software system, a decentralized, functionally closed, automated manufacturing platform for cell therapies (using Lonza’s Cocoon®) and a proprietary quality control testing and release strategy.

About Galapagos We are a biotechnology company with operations in Europe and the U.S. dedicated to developing transformational medicines for more years of life and quality of life. Focusing on high unmet medical needs, we synergize compelling science, technology, and collaborative approaches to create a deep pipeline of best-in-class small molecules and cell therapies in oncology and immunology. With capabilities from lab to patient, including a decentralized cell therapy manufacturing network, we are committed to challenging the status quo and delivering results for our patients, employees, and shareholders. For additional information, please visit  www.glpg.com  or follow us on  LinkedIn  or  X . 

T his press release contains inside information within the meaning of Regulation (EU) No 596/2014 of the European Parliament and of the Council of 16 April 2014 on market abuse (market abuse regulation).

For further information, please contact:

Forward-looking statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These statements are often, but are not always, made through the use of words or phrases such as “anticipate,” “expect,” “plan,” “estimate,” “will,” “continue,” “aim,” “intend,” “future,” “potential,” “could,” “indicate,” “forward,” as well as similar expressions. Forward-looking statements contained in this release include, but are not limited to, statements regarding Galapagos’ plans, expectations and strategy with respect to the ATALANTA-1 study, and statements regarding the expected timing, design and readouts of the ATALANTA-1 study, including the expected recruitment for such trials, statements related to the IND application for the Phase 1/2 ATALANTA-1 study. Forward-looking statements involve known and unknown risks, uncertainties and other factors which might cause Galapagos’ actual results to be materially different from those expressed or implied by such forward-looking statements. These risks, uncertainties and other factors include, without limitation, the risk that preliminary or interim clinical results may not be replicated in ongoing or subsequent clinical trials; the risk that ongoing and future clinical studies with GLPG5101 may not be completed in the currently envisaged timelines or at all, the inherent uncertainties associated with competitive developments, clinical trial and product development activities and regulatory approval requirements (including that data from the ongoing and planned clinical research programs may not support registration or further development of GLPG5101 due to safety, efficacy or other reasons), risks related to Galapagos’ reliance on collaborations with third parties (including its collaboration partner Lonza), the risk that Galapagos’ estimations regarding its GLPG5101 program and the commercial potential of GLPG5101 may be incorrect, as well as those risks and uncertainties identified in Galapagos’ Annual Report on Form 20-F for the year ended 31 December 2023 filed with the U.S. Securities and Exchange Commission (SEC) and its subsequent filings with the SEC. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The forward-looking statements contained herein are based on management’s current expectations and beliefs and speak only as of the date hereof, and Galapagos makes no commitment to update or publicly release any revisions to forward-looking statements in order to reflect new information or subsequent events, circumstances or changes in expectations.

1 Kersten, M.J., 2024. Seven-day vein-to-vein point-of-care–manufactured CD19 CAR T cells (GLPG5101) in relapsed/refractory non-Hodgkin lymphoma: Results from the Phase 1/2 ATALANTA-1 trial. EHA Library . Available at: https://bit.ly/3xZj9Mr [Accessed 09 July 2024]. 2 Throughout this press release, ‘Dr. Paul Stoffels’ should be read as ‘Dr. Paul Stoffels, acting via Stoffels IMC BV’.

• GLPG Press Release IND Clearance_ENG_FINAL

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Non-hodgkin lymphoma articles from across Nature Portfolio

Non-Hodgkin lymphoma is a cancer that affects lymphocytes, a type of white blood cells in the lymphatic system. They are generally classified according to the cancer's growth rate as high grade (fast growing) or low grade (slow growing).

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MEF2B C-terminal mutations enhance transcriptional activity and stability to drive B cell lymphomagenesis

N-terminal mutations in the transcription factor Myocyte Enhancer Factor 2B (MEF2B) are reported to drive lymphomagenesis. Here, the authors show that lymphoma-associated C-terminal mutations in MEF2B impair its phosphorylation, leading to increased stability and transcriptional activity to promote B-cell lymphomagenesis.

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New Center Provides Resources for HIV-Related Stigma Research

The National Institute of Mental Health has awarded Stefan Baral, MD , professor of Epidemiology , a $2.8 million, four-year P30 Center Core grant for the creation of the Center for HIV and Mental Health Stigma Elimination Strategies (CHIMES). The Center will provide resources to researchers whose focus is measuring and reducing HIV-related stigma and its impact on mental health.

“We are excited about the opportunities that CHIMES will bring to students and faculty in the Department of Epidemiology and other departments across the school in supporting pilot projects, grant writing support, and even open-access fees for papers for stigma-related projects,” said Baral.

A collaboration between the Bloomberg School of Public Health and Emory University Rollins School of Public Health, CHIMES is comprised of four cores, each with a specific aim:

Administrative Core: Build local and global capacity to measure and respond to stigma as a risk for suboptimal mental health and HIV outcomes.

Measurement Core: Improve the measurement of attribute-specific and intersectional stigmas on mental health and HIV.

Intervention Core: Increase the quantity and quality of interventions addressing stigma and structural determinants of risk.

Development Core: Support the proliferation of science in measuring and responding to stigma and structural determinants.

Sheree Schwartz, PhD , associate scientist in Epidemiology, is the Development Core director for the Center. Kalai Robinson, senior research program manager in Epidemiology, will serve as CHIMES manager supporting faculty and students with grant reviews, conference travel, and research paper support.

Together, these cores provide a wide range of free services to researchers, including analytical data access; mentorship for early-stage investigators; consulting services; technical support in research design, program development, and grant writing. Through CHIMES, investigators are welcome to contribute to collaborative, community-engaged conversations enabling pathways for idea generation; disseminate findings; and facilitate partnerships.

An online form highlights specific services available across CHIMES and provides the option to sign up for CHIMES updates. 

Questions about the Center can be sent to [email protected]

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3D-printed living cells pave way for tomorrow's medicine and cruelty-free animal products

3D printing has come a long way since its early days in the 1980s and is considered an essential tool in many manufacturing processes. Now, however, researchers like Italian bioengineer Dr Riccardo Levato, are taking the technique in a new and exciting direction.

What if, as well as car parts and designer furniture, we could print human organs or regenerate human tissue by bioprinting living cells?

Levato, an associate professor of biofabrication and regenerative medicine at the University Medical Center Utrecht and at Utrecht University, the Netherlands, leads a team of researchers from Belgium, Italy, the Netherlands, Sweden and Switzerland who received EU funding to do just that.

As part of a research initiative called  ENLIGHT which runs from 2021 to 2025, they are developing a miniature 3D-printed pancreas made of human cells. 

This, they hope, could improve the reliability and accuracy of testing of new therapies to treat diabetes and, perhaps, even one day lead to the possibility of lab-grown organs for human transplants.

Living blueprint

One of the key working materials of this research is stem cells. These are cells that have the potential to grow into many different types of human tissue – muscle cells, blood cells, brain cells – depending on the signals they receive.

Initial experiments, aimed at supporting patients with diabetes, have been carried out using insulin-producing cells grown in a lab from stem cells. Simply transplanting these cells into an ailing pancreas provides only short-term relief, however. According to Levato, this is because the cells lack proper support.

“ We essentially create a sort of light hologram of the object we want to print. Riccardo Levato, ENLIGHT

‘When you deliver these cells without structure, without vasculature, without protective material around them, they will die over time,’ he said. ‘The procedure lasts only a few years and then you have to repeat it.’

Levato and the ENLIGHT team are trying to fix this by 3D printing human tissue, living cells, to form three-dimensional implants complete with vessels. This is challenging because living cells are fragile and will not survive a normal 3D printing process.

The researchers have tackled this by using water-rich gels, called bioinks, that carry and nurture the cells during the printing process. They then need to be able to guide the process of cell differentiation so that the organ develops in line with its genetic “blueprint”. They do this using light.

Light touch 

The ENLIGHT researchers have developed a novel 3D printing technique that uses light to shape the cell-containing bioink, instead of squeezing it through a nozzle like in a conventional 3D printer, which would damage the cells.

‘We essentially create a sort of light hologram of the object we want to print in the middle of this medium,’ Levato said. 

‘Where you have this 3D light structure, the medium becomes solid and everywhere else it remains liquid so you can just wash it out. The cells are entrapped in the gelatine-like form, which is similar to the extra-cellular matrix in a living tissue.’

The researchers then nudge the cells to mature into insulin-producing cells by exposing them to light of specific wavelengths. 

The team is currently testing their implants in the laboratory and researchers hope such 3D printed organoids can become part of standard drug development procedures before the end of the decade. 

Levato cautioned, however, that it would take quite a bit longer to make the bioprinted organoids suitable for transplantation into human patients.

Cruelty-free

One of the advantages of the ENLIGHT team’s work is that it could greatly reduce the need for animal testing. Being able to print life-like human organoids would not only improve the accuracy of drug testing, but would mean that the suffering of millions of laboratory animals could be avoided. 

Dr Massimo Vassalli, a professor of bioengineering at the University of Glasgow in the UK, is taking the concept of 3D printing of living tissue in a slightly different direction, but one that could also potentially relieve animal suffering. 

He leads a multi-country EU-funded research initiative called  PRISM-LT which aims to develop cost-effective 3D printing of a variety of living tissues. Their work, which will run until 2027, could have relevant applications in both biomedicine and food production.

“ We see a big role for 3D bioprinting in sustainable and clean food production. Massimo Vassalli, PRISM-LT

‘The aim of the project is to create a platform technology to address the manufacturing of a diverse range of living tissues for application in the healthcare and food industries,’ said Vassalli. ‘In fact, beyond the more obvious medical uses, we see a big role for 3D bioprinting in sustainable and clean food production,’ he said.

The challenge, according to Vassalli, is to create complex heterogeneous tissues that truthfully mimic the texture of living materials. For example, meat contains muscle cells and fat cells, but also cells that form the connective tissues. 

To create meat that feels like the real thing, the researchers need to find ways to instruct stem cells to produce exactly the required type of tissue within a pre-defined structure – and then sustain the process over time.

Refining differentiation

The researchers are exploring an approach that mimics symbiotic processes in nature. They are mixing bacteria or yeasts – which Vassalli calls worker or helper cells – with the stem cells in a 3D printing bioink to help guide the differentiation process. 

‘These cells are either bacteria or yeast that can sense the direction in which the cells are going and start producing chemicals to help them differentiate further,’ he said.

The team expect to be able to create centimetre-scale tissue cubes by the end of the project, focusing first on 3D-printed bone marrow for medical applications and a sample of marbled cultured meat. 

‘Bioprinting technology offers improved flexibility in the design of the final composition of the tissue. This meets the needs of personalised healthcare applications,’ said Vassalli.

‘Food will take longer because the scale-up of the technology will take a lot of energy. A 3D printer we use in a lab wouldn’t be suitable to produce meat for a population. There is a technological gap that needs to be closed.’

Research in this article was funded by the European Innovation Council (EIC). The views of the interviewees don’t necessarily reflect those of the European Commission. If you liked this article, please consider sharing it on social media.

• Bioeconomy research and innovation

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