MD Anderson is renowned for innovative cancer research, exceptional patient care, impactful educational programs and a focus on prevention. Our unmatched scale and resources move discoveries from the lab to the clinic and back again seamlessly and at record speed. Our unique collaborative environment yields breakthroughs that are transforming the field, the lives of patients and society.
Our clinical trials program is the largest of its kind in the world, allowing our patients to benefit faster than ever from the most cutting-edge and personalized care. From pioneering cellular therapies to the latest bispecific antibodies and targeted therapies, our work is leading to more personalized diagnoses, treatments and improved outcomes for patients.
At the 2023 ASH Annual Meeting and Exposition, our experts showcase their latest practice-changing work with colleagues from across the globe for large-scale discussion.
Keep up with presentation highlights from our experts as well as learn more about our pioneering research across the field of hematology below.
Featured articles
MD Anderson faculty member receives 2023 Honorific Award from the American Society of Hematology
Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson, has been honored with the E. Donnall Thomas Lecture and Prize from the American Society of Hematology (ASH) for her groundbreaking research to develop and advance innovative cell therapies for cancer using natural killer (NK) cells.
MD Anderson Research Highlights: ASH 2023 Special Edition
Featuring novel treatments for AML and large B-cell lymphoma, therapeutic strategies for multiple leukemias and improving patient outcomes after lymphocyte infusion
ABSTRACT: 620
Combining the JAK inhibitor ruxolitinib with the BCL-xL inhibitor navitoclax was twice as effective in reducing enlarged spleens – a major indicator of clinical improvement – compared with standard-of-care ruxolitinib monotherapy for adult patients with intermediate or high-risk myelofibrosis, a rare bone marrow cancer, according to results of the Phase III TRANSFORM-1 trial reported by researchers from The University of Texas MD Anderson Cancer Center.
Data from the global, randomized, placebo-controlled clinical trial were presented today at the 2023 American Society of Hematology (ASH) Annual Meeting by Naveen Pemmaraju, M.D., professor of Leukemia. At the time of data cut-off, 63.2% of patients who received ruxolitinib and navitoclax achieved a spleen volume reduction of at least 35% within 24 weeks, compared to 31.5% of patients receiving ruxolitinib plus placebo, meeting the study’s primary endpoint.
“By adding a second drug to an approved therapy, we were able to improve spleen volume reduction compared to the current standard of care. This is an important measurement of the clinical benefits of this novel drug combination because treatments can be less effective when the spleen remains enlarged,” Pemmaraju said. “If we can treat myelofibrosis earlier on in the disease course, we may have an opportunity to impact overall disease modification, improve patient outcomes and reduce symptom burden.”
Currently, there are few Food and Drug Administration-approved drugs for the treatment of myelofibrosis. Available options provide patients with spleen and symptom improvement, but a substantial unmet need remains for therapies that provide durable spleen size reduction and other longer-term clinical. Allogenic stem cell transplants are an effective treatment option, but not all patients qualify.
This international trial enrolled 252 patients with intermediate or high-risk myelofibrosis and measurable spleen enlargement who had not received prior JAK inhibitor treatment. The trial randomized 125 patients to receive the navitoclax and ruxolitinib combination and 127 patients to receive ruxolitinib plus placebo. Most patients were male (57%) and the median age was 69.
The trial met its primary endpoint of spleen volume reduction at 24 weeks. Spleen volume reduction at any time was achieved by 77% of patients on the combination arm and 42% of patients on the control arm. The median time to first spleen volume reduction response was 12.3 weeks with the combination and 12.4 weeks with monotherapy. At 24 weeks, there were no significant differences between the groups in a myeloproliferative neoplasm symptom assessment, a secondary endpoint of the study.
Patients treated with the combination therapy, patients experienced side effects that were manageable and consistent with previous trials. The most common treatment-related side effects were thrombocytopenia, anemia, diarrhea and neutropenia. Serious adverse events were experienced by 26% of patients on the combination arm and 32% on the control arm.
“This study marks a notable achievement in the field of myelofibrosis, as one of the first reported global Phase III frontline randomized combination clinical trials in our field,” Pemmaraju said. “This dataset now opens the door for additional research and investigation into combination therapies to treat myelofibrosis and, importantly, highlights a potential new era of investigating disease modification for patients. Additional data from the TRANSFORM-1 study is being evaluated.”
The trial was funded by AbbVie. Pemmaraju receives research support from AbbVie. A full list of co-authors and their disclosures may be found here.
Two clinical trials led by researchers from The University of Texas MD Anderson Cancer Center demonstrated early positive results from novel therapies targeting menin for the treatment of relapsed or refractory acute leukemias with specific genetic alterations. Results from the studies were shared today in oral presentations at the 2023 American Society of Hematology (ASH) Annual Meeting. More information on all ASH Annual Meeting content from MD Anderson can be found at MDAnderson.org/ASH.
Menin inhibitor monotherapy reduces disease burden in majority of relapsed or refractory acute leukemia patients (Abstract 57)
According to data from a Phase I trial led by Elias Jabbour, M.D., professor of Leukemia, the menin inhibitor JNJ-75276617 showed early clinical activity in patients with relapsed or refractory acute leukemias and genetic alterations in KMT2A or NPM1, which are associated with poor clinical outcomes.
Among 66 patients able to be evaluated after one month of treatment, JNJ-75276617 monotherapy reduced bone marrow disease burden in 71%, and 33 of those patients had a decrease in bone marrow blasts of more than 50%. Median time to first response was less than two months. Similar response rates were observed across patient groups with both genetic alterations.
“Patients with relapsed or refractory leukemias and KMT2A or NPM1 alterations often do poorly on currently available therapies, so there is a need to advance more effective options,” Jabbour said. “We are encouraged by the antileukemic activity of this monotherapy, which mimics what we saw in the preclinical setting.”
In the multi-center clinical trial, researchers took a stepwise approach in evaluating the safety and efficacy of JNJ-75276617, a potent and selective inhibitor of the interaction between the scaffolding protein menin and the methyltransferase KMT2A. Eighty-six patients who had acute leukemias with NPM1 & KTM2A genetic alterations were included in the trial.
Patients received the therapy orally on a 28-day cycle. Fifty-six percent of evaluable patients had AML with KMT2A alterations and 43% of evaluable patients had NPM1 alterations. The median age of trial participants was 63 years, while the median number of prior therapies was two.
Differentiation syndrome was the most common side effect in patients but was overcome with step-up dosing. The trial is ongoing to determine the recommended Phase II dose.
The trial is sponsored by Janssen Pharmaceuticals. A complete list of collaborating authors and their disclosures can be found with the abstract.
Oral therapy combination shows promising results for advanced acute leukemias (Abstract 58)
The Phase I/II SAVE trial, led by Ghayas Issa, M.D., assistant professor of Leukemia, combined the menin inhibitor revumenib with venetoclax and hypomethylating agent ASTX727, yielding encouraging responses in adult and pediatric patients with relapsed or refractory advanced acute myeloid leukemia (AML) with KMT2A or NUP98 rearrangements or NPM1 mutations.
The overall response rate among nine evaluable patients was 100%. Three patients achieved complete remission, one patient achieved complete remission with partial hematologic recovery, and three patients had complete remission with incomplete platelet count recovery. In addition, one patient had a partial response and one had a morphologic leukemia-free state. Measurable residual disease was undetectable in six of the patients.
“These advanced and acute leukemias often are very difficult to treat and currently have no approved targeted therapies. We believe these early results suggest this treatment will be highly effective in advanced leukemias,” Issa said. “This is our first look at an entirely oral combination therapy using menin inhibitors, and the results are very encouraging. If sustained in further trials, this could lead to a change in the standard of care for this patient population, with great potential to improve their quality of life.”
Revumenib is a potent, oral, selective inhibitor of the menin-KMT2A interaction. To date, nine patients aged 12 years and older have been enrolled in the trial. Of those, five patients had KMT2A rearrangements, three had NUP98 rearrangements and one had mutant NPM1. On average, patients had received three prior lines of therapy.
Side effects were manageable and consistent with previous studies. The trial is ongoing, with plans to establish the recommended Phase II dose and optimize delivery of the combination before enrolling patients in the Phase II cohort.
This investigator-initiated study was supported by Syndax and Astex. A complete list of collaborating authors and their disclosures can be found with the abstract.
ABSTRACT: LBA-2
The targeted therapy combination of ibrutinib and venetoclax significantly improved progression-free survival (PFS) and achieved an overall remission rate in 82% of patients with relapsed/refractory mantle cell lymphoma (MCL), according to researchers at The University of Texas MD Anderson Cancer Center. Results from the Phase III SYMPATICO trial were presented at the 2023 American Society of Hematology (ASH) Annual Meeting.
At a median follow-up of 51.2 months, median PFS was 31.9 months with the combination compared to 22.1 months with ibrutinib plus placebo. PFS benefits were consistent across patient subgroups, including those with blastoid-variant or TP53-mutated MCL. On the combination arm, 54% of patients achieved a complete remission compared to 32% on the placebo arm, a significant improvement.
“We are very encouraged by the data from this trial and for our patients to have achieved remissions using this targeted therapy. This combination allowed us to attack the cancer cells in two ways, which made it harder for the tumor to find resistance,” said principal investigator Michael Wang, M.D., professor of Lymphoma & Myeloma.
This international, multi-center trial evaluated ibrutinib, a BTK inhibitor, paired with venetoclax, a BCL-2 inhibitor; the two work together to attack MCL cells. MCL is a rare type of non-Hodgkin lymphoma with about 4,000 new cases diagnosed each year in the U.S. Often is diagnosed at stage IV, MCL has an aggressive disease course. According to Wang, MCL is becoming more common as the population ages.
The trial enrolled 267 adults with relapsed/refractory MCL who had previously received at least one prior line of therapy. Patients were randomly assigned to receive ibrutinib and venetoclax or ibrutinib and placebo.
Side effects were manageable and consistent with previous studies. Grade 3 or higher adverse events occurred in 84% of patients treated with the combination and 76% of those on the placebo arm. The most common side effect experienced was neutropenia.
“I am encouraged by our findings as we work to identify effective, targeted, chemo-free treatment options for patients with MCL,” Wang said. “We look forward to longer follow-up data from this trial to determine the best therapeutic approach for these patients. This is a milestone achievement for our patients with MCL.”
The trial was supported by AbbVie. A complete list of collaborating authors and their disclosures can be found with the abstract.
ABSTRACT: 77
The targeted therapy bezuclastinib was safe and rapidly reduced markers of disease burden while also improving symptoms for patients with a rare blood disorder called nonadvanced system mastocytosis, according to results of the Phase II SUMMIT trial reported by researchers at The University of Texas MD Anderson Cancer Center.
The findings, presented today at the 2023 American Society of Hematology (ASH) Annual Meeting, demonstrate that all participants treated with bezuclastinib achieved at least a 50% reduction in markers of disease burden and 63% reported their disease symptoms eased within 12 weeks. That number increased to 78% after an additional eight weeks of treatment, at which time all patients also reported an improvement in pain symptoms.
“The era of targeted therapy offers hope, not just for alleviating symptoms but for getting to the root of the condition,” said principal investigator Prithviraj Bose, M.D., professor of Leukemia. “Bezuclastinib provides precision targeting without the typical central nervous system or bleeding side effects often associated with similar drugs."
Systemic mastocytosis (SM) is a rare disease marked by the buildup of malignant mast cells in the bone marrow and other tissues. These high levels of abnormal mast cells can lead to a multitude of symptoms due to the release of chemicals called mediators. SM can range from non-advanced (NonAdvSM) to advanced disease (AdvSM), with symptoms that can include brain fog and skin rashes to gut issues and life-threatening anaphylaxis.
In up to 95% of patients, SM is driven by the KIT D816V gene mutation. Treatments targeting this mutated kinase have been used for AdvSM variants, but they are known to have off-target activity that can cause toxicities that restrict dosing and, therefore, limit efficacy.
There are two variants within NonAdvSM: indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM). ISM, which affects the majority of patients with SM, is characterized mostly by symptoms related to mast cell degranulation and mediator release. SSM is identified by a higher mast cell burden, marked by high levels of blood enzymes like serum tryptase, but without resulting organ damage.
Bezuclastinib is a potent type-1 tyrosine kinase inhibitor that blocks mutant KIT D816V activity while sparing other kinases, minimizing the potential for off-target side effects. In a separate, prior studies, the drug demonstrated minimal brain penetration in lab models and no central nervous system toxicities in patients with AdvSM.
The first part of the SUMMIT trial followed 20 patients with NonAdvSM for a median duration of seven months. The majority were female (75%) with a median age of 50. Seventy-five percent of patients had the KIT D816V mutation, and all had moderate-severe symptoms. Patients were treated with either 100 or 200 mg of bezuclastinib or with placebo. All patients continued to receive their baseline anti-mediator treatments throughout the trial.
Researchers evaluated the efficacy of bezuclastinib through multiple patient-reported outcome measures and changes in markers of disease burden, such as serum tryptase, bone marrow mast cell percentage and KIT D816V mutation allele burden.
Patients who received the 100 mg dose experienced a median reduction in symptoms of 48.5% after 12 weeks. During this period, none of the patients in the placebo group reported significant improvement in their overall symptoms. However, after transitioning those patients to bezuclastinib treatment, 67% reported an improvement in their symptoms after four weeks.
After 20 weeks, more patients observed greater improvements in dermatological symptoms (78%), gastrointestinal symptoms (33%) and cognitive symptoms (33%) compared to the 12-week mark.
Adverse events generally were mild and reversible, with the most frequent being a change in hair color, nausea and peripheral edema. No serious adverse events related to bezuclastinib were reported in the 100 mg or 200 mg cohorts.
"This drug may offer great promise in the treatment of non-advanced systemic mastocytosis," Bose said. "As we move forward, our aspiration is to optimize the dosage while maintaining a robust safety profile.”
To further assess the drug’s efficacy in patients with NonAdvSM, next steps for the SUMMIT trial include comparing bezuclastinib against placebo once the optimal dose is known with certainty. Part Ib of the trial will investigate 100mg and 150 mg daily doses that use a different formulation of the drug, and those results are expected in 2024, Bose explained.
The SUMMIT trial was sponsored by Cogent Biosciences. Bose reports relationships with Cogent Biosciences, GSK, Novartis, Karyopharm, AbbVie, PharmaEssentia, Jubilant, Morphic, Kartos, Telios, Disc, Jassen, Geron, Ionis, Incyte, Bristol Myers Squibb, Sobi, MorphoSys, Blueprint and Sumitomo. A full list of co-authors and disclosures can be found with the abstract.
Meet the Experts
Stop by booth 122 to ask a question, learn about training and career opportunities and continue the conversation on key presentations with our experts. See the full schedule below.
Monday, Dec. 11
10–10:30 a.m.
Updates in aggressive B-cell lymphomas
Francisco Vega, M.D., Ph.D.
Hematopathology
Jason Westin, M.D.
Lymphoma
12:30–1 p.m.
The next generation of trailblazers, part 2
Fadi Haddad, M.D.
Leukemia
Paolo Strati, M.D.
Lymphoma
1–1:30 p.m.
MD Anderson Cancer Network®: Partnering to eliminate cancer
Tulin Budak-Alpdogan, M.D.
MD Anderson Cancer Center at Cooper
Rajneesh Nath, M.D.
Banner MD Anderson Cancer Center
Naveen Pemmaraju, M.D.
Director of Leukemia for Cancer Network
Sunday, Dec. 10
10–10:30 a.m.
Insights on cellular therapies
Yago Nieto, M.D., Ph.D.
Stem Cell Transplantation & Cellular Therapy
Katy Rezvani, M.D., Ph.D.
Stem Cell Transplantation & Cellular Therapy
Elizabeth Shpall, M.D.
Chair, Stem Cell Transplantation & Cellular Therapy
11:30 a.m.–12 p.m.
New targets in leukemia: Menin and FLT3
Naval Daver, M.D.
Leukemia
Elias Jabbour, M.D.
Leukemia
Sanam Loghavi, M.D.
Hematopathology
Musa Yilmaz, M.D.
Leukemia
12–12:30 p.m.
Focus on chronic lymphocytic leukemia
William Wierda, M.D., Ph.D.
Leukemia
12–12:30 p.m.
Training at MD Anderson, part 1
Qaiser Bashir, M.D.
Stem Cell Transplantation Fellowship
Sanam Loghavi, M.D.
Hematopathology Fellowship
12:30–1 p.m.
Advances in stem cell transplants
Uday Popat, M.D.
Stem Cell Transplantation & Cellular Therapy
Muzaffar Qazilbash, M.D.
Stem Cell Transplantation & Cellular Therapy
4–4:30 p.m.
Training at MD Anderson, part 2
Guillermo Garcia-Manero, M.D.
Leukemia Fellowship
Tapan Kadia, M.D.
Leukemia Fellowship
Krina Patel, M.D.
Hematology/Oncology Fellowship
Dristhi Ragoonanan, M.B.B.S.
Pediatric Hematology and Oncology Fellowship
Pediatric Stem Cell Transplantation Fellowship
Irtiza Sheikh, D.O.
Pediatric Hematology and Oncology Fellowship
Pediatric Stem Cell Transplantation Fellowship
Saturday, Dec. 9
11–11:30 a.m.
New approaches to myelodysplastic syndrome
Simona Colla, Ph.D.
Leukemia
12–12:30 p.m.
The next generation of trailblazers, part 1
Hussein Abbas, M.D., Ph.D.
Leukemia
Luis Malpica Castillo, M.D.
Lymphoma
1–1:30 p.m.
Emerging therapies and novel combinations: Challenging the standard of care
Ghayas Issa, M.D.
Leukemia
Hans Lee, M.D.
Multiple Myeloma
1–4 p.m.
Peter WT Pisters, M.D.
MD Anderson President
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Related research from our experts
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, or MALT lymphoma, is a slow-growing type of non-Hodgkin lymphoma that develops in the lymphoid tissue outside the lymph nodes.
MALT lymphoma is the most common form of marginal zone lymphoma, though it’s still rare. It’s estimated that about 5,000 new cases of MALT lymphoma are diagnosed in the U.S. each year, according to lymphoma specialist Dai Chihara, M.D., Ph.D.
To learn more about this disease, we spoke with Chihara and radiation oncologist Jillian Gunther, M.D., Ph.D. Here’s what they shared.
Where does MALT lymphoma develop?
The stomach is the most common site for MALT lymphoma. This is known as gastric MALT lymphoma. It can also be found in other parts of the gastrointestinal tract.
“It’s important to note that this is not a primary stomach cancer,” says Gunther. “This is lymphoma that occurs in the stomach.”
Non-gastric MALT lymphoma most commonly affects the lungs, salivary glands, tissues around the eye and skin.
What are the symptoms of MALT lymphoma?
Symptoms can vary, depending on where the lymphoma is in the body. Some people may not have any symptoms, and the cancer is found incidentally when a doctor is testing for something else.
For gastric MALT lymphoma, symptoms often mimic those of an upset stomach and can include:
- abdominal pain
- bloating
- heartburn
- acid reflux
Non-gastric MALT lymphoma may cause the following symptoms, depending on where it occurs in the body:
- salivary gland: a mass you can feel or that shows up in imaging
- lung: cough or shortness of breath
- skin: a small bump on the skin that can resemble a bug bite or pimple
“If you have any of these symptoms for longer than a couple of weeks without improvement, or if the symptoms are worsening, you should see a doctor to be evaluated,” says Gunther.
What causes MALT lymphoma?
Some MALT lymphomas are associated with autoimmune disorders and infections, depending on where the lymphoma is located.
Helicobacter pylori (H. Pylori) infection, a common bacterial infection that can cause stomach ulcers, increases the risk for gastric MALT lymphoma. Many gastric MALT lymphoma patients will have an H. Pylori infection.
“The H. Pylori infection causes chronic inflammation in the stomach, which is thought to increase the risk of gastric MALT lymphoma,” says Chihara.
MALT lymphoma on the skin may be linked to Borrelia burgdorferi infection, while the autoimmune disorder Sjogren’s syndrome can increase the risk of MALT lymphoma in the salivary glands.
How is MALT lymphoma diagnosed?
Doctors need biopsies to diagnose MALT lymphoma. The type of biopsy depends on where the lymphoma has developed.
An interventional radiology image-guided biopsy may be used to diagnose MALT lymphoma in the salivary glands or lungs. A bronchoscopy can also be used for the lungs.
An endoscopy may be used to diagnose gastric MALT lymphoma.
After a MALT lymphoma diagnosis is made, doctors will try to determine the cancer stage.
“With MALT lymphoma, it’s more common for patients to be diagnosed with early-stage disease, or localized disease that hasn’t spread to distant lymph nodes or other parts of the body,” says Gunther.
The cancer’s stage determines the treatment.
How is MALT lymphoma treated?
Patients with gastric MALT lymphoma can be given antibiotics first to treat H. Pylori. Treating the infection often clears away the lymphoma.
If antibiotics don’t work, patients with early-stage MALT lymphoma receive radiation therapy.
If MALT lymphoma is not localized, and if you’re not experiencing any problems from the cancer, your doctor may choose to monitor you closely, rather than prescribing treatment.
“MALT lymphoma is often a very slow-growing disease, and people can live with it for long periods, sometimes without even knowing they have it,” says Gunther. “MALT lymphoma is treatable in most cases. We don’t want to cause the patient more harm with the treatment than the disease itself.”
For patients with progressive advanced-stage MALT lymphoma that is causing symptoms or trouble, there are systemic treatment options.
The first systemic treatment option is the monoclonal antibody rituximab or chemoimmunotherapy, which is a combination of chemotherapy and immunotherapy. You may be given a chemotherapy drug, such as CHOP or bendamustine plus rituximab.
Recurrent MALT lymphoma may be treated with oral drugs, such as BTK inhibitors ibrutinib and zanubrutinib, or the immunotherapy drug lenalidomide.
What new research is being done to advance MALT lymphoma treatment?
Gunther recently led a clinical trial looking at reducing the radiation dosage for gastric MALT lymphoma patients.
“In the past, the standard dose for radiation was at least two-and-a-half weeks of treatment. But because of the positive response to low-dose radiation in this type of cancer, we’ve been looking to reduce the dose,” explains Gunther.
In the clinical trial, patients started with ultra-low-dose radiation, or just two days of treatment.
“We gave additional treatment — another 10 days of radiation — only to those patients who did not experience a complete response after the initial two days,” she says. “This spared a majority of patients unnecessary treatment and side effects.”
Because MALT lymphoma is rare, more research is needed to help determine which treatments work best for patients with MALT lymphoma. But Chihara notes that MD Anderson continues to pursue new clinical trials with the goal of expanding treatment options for patients with MALT lymphoma.
Request an appointment at MD Anderson online or by calling 1-877-632-6789.
For many patients diagnosed with certain types of B-cell lymphoma, leukemia and multiple myeloma, chimeric antigen receptor (CAR) T cell therapy offers an effective treatment option. This cellular therapy is created by extracting a patient’s T cells, modifying them in a lab to identify and attack cancer cells, and returning them to the patient.
The process of creating the CAR T cells can take three to four weeks. Radiation therapy can be a tool to help get a patient through this manufacturing period. This is called bridging therapy.
“Bridging therapy can help control the disease so that a patient can get to the CAR T cell infusion,” says radiation oncologist Penny Fang, M.D. Research from Fang and her colleagues examines the role of bridging therapy for B-cell lymphoma patients receiving CAR T cell therapy. Their latest findings will be presented at the 2023 American Society for Radiation Oncology Annual Meeting.
Radiation therapy can relieve cancer-related symptoms
Currently, bridging therapy is often used ahead of CAR T cell therapy in patients who have large tumors or tumors that are causing symptoms such as pain or weakness. It can also be used to reduce the risk of symptoms in patients with tumors in or near important areas of the body.
Patients who have had prior radiation may still be eligible for bridging therapy, Fang says.
Ongoing work examines the effect of radiation therapy on CAR T cell therapy efficacy
In addition to managing tumor-related symptoms, radiation therapy reduces the number of tumor cells. “By scaling down the job for the CAR T cells, we can potentially optimize their success,” Fang says.
The more tumor cells that are eliminated with radiation therapy before CAR T cell therapy, the less work the CAR T cells have to do. “Ultimately, the goal of CAR T cell therapy is cure, and we hope to help get there with radiation therapy,” Fang says.
At the ASTRO Annual Meeting, Fang and her colleagues will present findings that show patients who can feasibly be treated with radiation therapy at all the involved tumor sites tend to have more favorable outcomes.
“We have ongoing work now to try to understand why that may be the case,” Fang says.
Bridging therapy may prime the tumor microenvironment and the tumor cells
Reducing the tumor volume may not be the only benefit of bridging therapy. Fang and her colleagues are conducting clinical trials to explore the advantages of radiation therapy in patients receiving CAR T cell therapy. They’re looking at whether lower dose radiation can help modify the tumor microenvironment and help with tumor cell death.
“We’re studying whether therapy may be priming the tumor microenvironment and/or systemic immune state so that the CAR T cells may more effectively do their work,” Fang says.
Radiation therapy may benefit patients who don’t experience a complete response to CAR T cell therapy
Fang and her colleagues also are investigating whether radiation therapy can be used to modify the immune response and jumpstart idle CAR T cells in patients who don’t experience a complete response to CAR T cell therapy.
An ongoing study is investigating whether radiation may be synergistic with CAR T cell therapy in patients with multiple myeloma who don’t completely respond to treatment. “Our question is: if there’s disease resistant to CAR T cells, can we potentially improve the response with radiation,” Fang asks.
Research aims to expand understanding of radiation therapy’s impact on CAR T cell therapy
Fang and her colleagues are conducting more research to better understand the synergy of radiation therapy and CAR T cell therapy. For example, they have an ongoing umbrella clinical study looking at patients across multiple hematologic malignancies who are being treated with radiation therapy and CAR T cell therapy.
“We’re also planning to analyze patients’ blood biomarkers so that we can better quantify the immune response after radiation therapy and how it may potentially synergize with CAR T cell therapy to improve outcomes for more patients,” Fang says.
Request an appointment at MD Anderson online or by calling 1-877-632-6789.
Lymphoma is often thought of as a cancer of lymph nodes, but it's actually a cancer of the lymphocytes. Lymphocytes are white blood cells that manage inflammation in the body.
Chronic inflammation can sometimes lead to a lymphoma known as marginal zone lymphoma.
Marginal zone lymphoma is a rare, slow-growing B-cell lymphoma. Because it’s so rare, marginal zone lymphoma is often treated like other subtypes of B-cell lymphomas, and new treatment options are often explored through clinical trials that group marginal zone lymphoma with other B-cell lymphoma subtypes.
But lymphoma expert Paolo Strati, M.D., and a team at MD Anderson has changed the treatment landscape for patients facing this rare diagnosis by conducting a practice-changing clinical trial. We spoke with him to find out what patients and caregivers should know about the disease, including symptoms and current treatments, as well as his team’s new research. Here’s what he shared.
1. Marginal zone lymphoma has three subtypes.
Marginal zone lymphoma is a rare type of non-Hodgkin lymphoma. It develops from chronic inflammation or because of a random error in DNA that leads to the creation of abnormal cells. It can be categorized into three subtypes:
- Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue – Often called MALT lymphoma, this subtype is found outside of the lymph nodes. It’s commonly found in the stomach, but it can also be found in the eyes, the bowels and the skin.
- Nodal – Nodal lymphoma is what often comes to mind when thinking of lymphoma, but it’s the second most common subtype. That’s because it’s found in the lymph nodes. It’s also more frequently studied since it’s easier to follow.
- Splenic – The rarest subtype of marginal zone lymphoma is splenic. It affects the spleen, an organ in the chest that is part of the immune system and helps filter blood.
Marginal zone lymphoma is also more commonly diagnosed in people over age 65.
2. Marginal zone lymphoma can grow for years before the first symptoms appear.
Because marginal zone lymphomas are slow-growing, it can take years for a patient to experience symptoms. That’s why it’s often discovered by chance when a patient has testing for another medical reason.
Although the splenic subtype affects the spleen, the cancer doesn’t show up as tumors in the organ. Instead, the spleen gets enlarged. With nodal marginal zone lymphoma, the lymph nodes become enlarged.
MALT lymphoma is different in that it tends to show up like inflammation. Patients may have discharge at the eye, so it’s thought to be conjunctivitis. Or, patients will have symptoms aligning with gastritis, which is when the stomach lining is inflamed. They’ll feel stomach pain or experience vomiting. Or, if it’s affecting the skin, the patient will have a rash.
3. Treatments can vary, depending on where you seek care.
30% to 40% of patients diagnosed with some MALT lymphomas see it clear away with antibiotics. Radiation therapy may be used for patients whose disease is more advanced and not responding to antibiotics.
Patients with splenic marginal zone lymphoma often receive a treatment type called biologics. An example is the monoclonal antibody rituximab.
Nodal marginal zone lymphoma is often treated like other B-cell lymphomas, so many patients receive chemotherapy. However, chemotherapy and its side effects can be very difficult for older patients.
Patients treated at specialized cancer centers like MD Anderson may receive chemotherapy-immunotherapy combination regimens like bendamustine and rituximab or R-CHOP. Or, they may receive immunotherapy with lenalidomide and rituximab, which we call R2.
Specialized cancer centers can also offer patients with relapsed disease another treatment option called BTK inhibitors. BTK is a receptor present in every B cell. It’s particularly overexpressed in lymphoma B cells, and it’s critical to their survival. BTK inhibitors are cancer drugs that target the BTK receptor to clear our abnormal B cells.
4. Better marginal zone lymphoma treatment options are now available, thanks to MD Anderson research.
When patients can access BTK inhibitors, they often receive a drug called ibrutinib. But it's not very specific in targeting the BTK receptor. It also targets other proteins, which can increase the risk of side effects, including bleeding, atrial fibrillation, high blood pressure, diarrhea and joint pain. Because of these challenges, many patients opt to switch to another treatment after several cycles.
For the last few years, MD Anderson has been leading a clinical trial to investigate treating marginal zone lymphoma with another BTK inhibitor called acalabrutinib. Compared with ibrutinib, the inhibition is specific to BTK and not spread across other proteins. Therefore, it’s more effective, and patients experience few side effects.
Because of the benefits to patients and the limited side effects, ibrutinib has been removed from the National Comprehensive Cancer Network treatment guidelines and acalabrutinib along with another BTK inhibitor called zanubrutinib has been added.
MD Anderson has really led this study. It's not just the principal investigator, but the study coordinators, the data coordinators, our regulatory people. It's been a team effort, and we’re incredibly proud to offer patients a more effective option with fewer side effects.
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