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Tag: University of Texas MD Anderson Cancer Center

  • MD Anderson and C-Biomex sign collaborative research agreement to co-develop CBT-001 radioligand therapy

    MD Anderson and C-Biomex sign collaborative research agreement to co-develop CBT-001 radioligand therapy


    Newswise — HOUSTON & POHANG, South Korea – The University of Texas MD Anderson Cancer Center and C-Biomex Ltd. today announced a strategic research collaboration agreement to co-develop CBT-001, a radioligand targeting the CA9 cancer biomarker. 

    This collaboration brings together MD Anderson’s expertise in translational radiopharmaceutical research with C-Biomex’s differentiated radioligand. The principal investigator for this project is H. Charles Manning, Ph.D., professor of Cancer Systems Imaging and director of the Cyclotron Radiochemistry Facility at MD Anderson. Under the agreement, MD Anderson and C-Biomex plan to conduct preclinical studies of CBT-001 to evaluate its potential for translation into early-phase clinical studies and to support an anticipated Investigational New Drug (IND) application with the Food and Drug Administration (FDA). 

    “With our global expertise in the design and discovery of differentiated peptide-ligands, Dr. Manning and the team at MD Anderson provide a perfect complement to advance the preclinical and clinical development of CBT-001,” said Cha JunHoe, Ph.D., chief executive officer of C-Biomex. “We hope this collaborative research allows us to move swiftly toward an FDA IND application and, ultimately, to an approved treatment that can benefit patients with a variety of cancers.”

    CBT-001 is a radiolabeled isotope (Lutetium-177) attached to a proprietary peptide-ligand targeting CA9 (carbonic anhydrase 9), a biomarker overexpressed in various cancers, including renal, breast and lung cancers. CBT-001’s differentiated early-stage data, generated by C-Biomex in collaboration with the Korea Institute of Radiological and Medical Sciences, represents a strong foundation for this collaborative research.

    The key to success with this type of molecule is specific delivery to the tumor and rapid clearance, with minimal accumulation in healthy cells. Through this research, the collaborators will evaluate systemic and tumor-specific uptake of CBT-001 as well as antitumor efficacy and toxicology in preclinical models.

    C-Biomex, leveraging its unique CUSTM peptide discovery platform technology, is developing CBT-001 and several next-generation radioligand therapies with optimal characteristics. The collaborators anticipate this research will help to inform future preclinical and early-stage clinical investigations of these next-generation therapies.

    “We are pleased to align our broadly engaged theranostics research team at MD Anderson with our colleagues at C-Biomex to advance the development of CBT-001,” Manning said. “We have seen encouraging early data with this radioligand, and we look forward to collaborative work as we seek to bring impactful new treatment options to our patients in need.”

    Under the terms of the agreement, C-Biomex will provide research support funding, and MD Anderson is eligible to receive certain royalties and payments based on a range of future development milestones.

    Read this press release in the MD Anderson Newsroom.

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    About C-Biomex

    C-Biomex, a private preclinical-stage biopharmaceutical company founded in 2017, is focused on developing innovative radioligand therapies with its proprietary platform technology, CUSTM (Chemistry-based Ultra-Sensitive peptide discovery). C-Biomex’s peptides have demonstrated exceptional tumor binding and selectivity with fast clearance through the renal system. The company is innovating peptides to bring better radioligand therapies to patients with cancer.

    About MD Anderson

    The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world, and, in 1971, it became one of the nation’s first National Cancer Institute (NCI)-designated comprehensive cancer centers. MD Anderson is No. 1 for cancer in U.S. News & World Report’s “Best Hospitals” rankings and has been named one of the nation’s top two hospitals for cancer since the rankings began in 1990. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672).





    University of Texas MD Anderson Cancer Center

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  • ASH: Novel combination therapy significantly reduces spleen volume in patients with myelofibrosis

    ASH: Novel combination therapy significantly reduces spleen volume in patients with myelofibrosis

    Newswise — SAN DIEGO ― 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 modificationimprove 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.

    Read this press release in the MD Anderson Newsroom.

    University of Texas MD Anderson Cancer Center

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  • ASH: Targeted oral therapy reduced disease burden and improved symptoms for patients with rare blood disorder

    ASH: Targeted oral therapy reduced disease burden and improved symptoms for patients with rare blood disorder

     Newswise — SAN DIEGO ― 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 animals 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 futher 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 determined. 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.

    Read this press release in the MD Anderson Newsroom.

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  • ASH: Novel menin inhibitors show promise for patients with advanced acute myeloid leukemias

    ASH: Novel menin inhibitors show promise for patients with advanced acute myeloid leukemias

    Newswise — 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.

    Read this press release in the MD Anderson Newsroom.

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  • MD Anderson announces Institute for Data Science in Oncology to advance mission to end cancer

    MD Anderson announces Institute for Data Science in Oncology to advance mission to end cancer

    Newswise — HOUSTON ― The University of Texas MD Anderson Cancer Center today announced the launch of its Institute for Data Science in Oncology (IDSO), which integrates the most advanced computational and data science approaches with the institution’s extensive scientific and clinical expertise to significantly improve patient’s lives by transforming cancer care and research.

    Bringing top data scientists from a variety of fields together with clinicians and cancer scientists, the institute builds on MD Anderson’s culture of collaboration and connectivity to tackle the field’s most pressing needs in new and innovative ways. IDSO’s efforts have been catalyzed by philanthropic and institutional support of more than $61 million, representing significant progress toward an initial fundraising goal of $100 million.

    “The answers to overcoming cancer are within our reach, and we owe it to our patients and their families to move beyond traditional approaches to find those answers quickly,” said David Jaffray, Ph.D., director of IDSO and chief technology and digital officer at MD Anderson. “The institute is changing the way we work, incorporating the next generation of computational approaches and team data science across MD Anderson. By making data part of every decision, we will ensure progress for our patients and their families at the pace needed to address the urgent problem of cancer.”

    MD Anderson generates an immense amount of data annually, including complex clinical information and expansive laboratory datasets. Building on the most advanced data and computational scientific methods available, IDSO is revolutionizing how the institution leverages data to fuel new discoveries, optimize the patient experience and personalize cancer care.

    “At MD Anderson, we are intimately familiar with the urgent needs and challenges facing our patients, and we will find the best solutions possible by unlocking the full power of the growing and increasingly complex data,” said Caroline Chung, M.D., director of Data Science Development and Implementation for IDSO and chief data officer at MD Anderson. “The institutional commitment to this effort enables us to build an unmatched oncology data ecosystem that fuels effective collaborations across MD Anderson and around the world.”

    Through its work, IDSO not only allows for better analysis of existing data but also changes how MD Anderson generates, collects and manages data. This comprehensive approach enables research and clinical teams to derive new and deeper insights that can be applied to accelerate drug discovery and development, to improve scheduling and access for patients, to enhance the safety and quality of care, and to allow for personalized treatment decisions based on results and predictions from diagnostic tests.

    “The Institute for Data Science in Oncology positions MD Anderson as a leader in data science for cancer care, discovery and clinical operations. Its innovative programs will be, in many cases, the first generation of data science applied to the challenge of ending cancer,” said Peter WT Pisters, M.D., president of MD Anderson. “The institute is a critical element of our institutional strategy, and it will transform how MD Anderson uses data to advance discoveries and make the greatest impact on humanity.”

    Teaming up on focused areas of opportunity

    The institute unites MD Anderson’s clinical and research communities in transformative data efforts, offering new opportunities for collaborations across the institution and with external researchers and industry colleagues. Located in the Texas Medical Center’s Helix Park and housed in the TMC3 Collaborative Building, IDSO brings together experts in medicine, science, academia and industry.

    Led by Jaffray and Chung, IDSO is engaging top data science experts to direct established focus areas. Current co-leads who already have joined IDSO include Bissan Al-Lazikani, Ph.D., professor of Genomic Medicine; Heiko Enderling, Ph.D., professor of Radiation Oncology; Jeffrey Siewerdsen, Ph.D., professor of Imaging Physics; and Yinyin Yuan, Ph.D., professor of Translational Molecular Pathology.

    IDSO is focused on five initial priority areas, selected based on alignment with clinical practice and the existing technology required for meaningful progress. These include:

    • Quantitative Analysis and Insights from Pathology and Medical Imaging
      Led by Chung and Yuan, this focus area is advancing automated tools and AI algorithms to tap into the information within medical imaging data, including radiology and pathology, creating tools to more rapidly diagnose and characterize cancer and to provide effective, predictive measures of treatment response to guide personalized treatments.
    • Multi-Cell Interactions Informed Through Single Cell Analytics and Data Science
      Aligning with MD Anderson’s strong basic science and bioinformatics community, IDSO is driving a deeper fundamental understanding of cancer biology to uncover new therapeutic opportunities. IDSO is collaborating with the James P. Allison Institute to strengthen data science capabilities in order to extract insights from the explosion of single cell and spatial transcriptomics data.
    • Computational Modeling for Discovery, Development and Optimization of Precision Medicine
      Led by Al-Lazikani and Enderling, this focus area is applying advanced computer modeling, novel AI techniques and digital twin approaches to discover, design and advance novel therapeutics and regimens. These efforts integrate with canSAR, the world’s largest public cancer drug discovery resource, now hosted at MD Anderson to benefit the research community worldwide.
    • Equitable Decision Analytics for the Health of the Person and Society
      IDSO is advancing data-driven, computationally informed approaches to support personal and societal decision making. By developing a more complete understanding of the multi-dimensional impact of cancer — personal, economic, and societal — we can explore innovations across the continuum of health to identify those with the greatest potential for impact.
    • Development of Automated Approaches to Increase Access, Safety and Quality
      Under the leadership of Siewerdsen, this focus area is building data-science expertise to optimize the patient experience for those seeking care at MD Anderson. Efforts include improving patient access, optimizing the quality of care, and maximizing the safety of our treatment environments.

    The institute continues to recruit top scientists from around the world and is training the next generation of pioneers in the field, creating a diverse and inclusive environment that facilitates seamless engagement with MD Anderson’s clinicians and researchers. The IDSO Fellows program, led by Christopher Gibbons, Ph.D., associate professor of Symptom Research, is designed to offer postdoctoral training opportunities for junior clinicians and researchers that will empower them to become leaders in data science for oncology.

    Together with Dan Shoenthal, chief innovation officer at MD Anderson, IDSO is engaging with leaders in the field to establish relationships that can advance priority initiatives, including ongoing initiatives with industry collaborators as well as The University of Texas at Austin Oden Institute for Computational Engineering and Sciences and the Texas Advanced Computing Center, Rice University and Break Through Cancer. 

    Philanthropic support accelerates the impact of data science

    Generous support from dedicated donors across the nation is accelerating the far-reaching, long-term possibilities of IDSO. Philanthropic investments enable the institute to hire and train exceptional talent and to rapidly build the necessary infrastructure to carry out its work, resulting in meaningful improvements for patients and their families.

    IDSO has received significant commitments from the Commonwealth Foundation for Cancer Research, Lyda Hill Philanthropies, the Hackett Family, the Laura and John Arnold Endowment and more, including an anonymous donor. Matching funds are expected from multiple organizations, including the Commonwealth Foundation.

    “The inspired actions of our donors speak volumes about the potential of this institute to make meaningful impacts on the next era of cancer research and care,” Jaffray said. “We are grateful for their boundless generosity and their dedication to our mission to end cancer.”

    Read this press release in the MD Anderson Newsroom.

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  • ESMO: Pre- and post-surgical immunotherapy improves outcomes for patients with operable lung cancer

    ESMO: Pre- and post-surgical immunotherapy improves outcomes for patients with operable lung cancer

    Newswise — MADRID ― Compared with pre-surgical (neoadjuvant) chemotherapy alone, adding perioperative immunotherapy – given before and after surgery – significantly improved event-free survival (EFS) in patients with resectable early-stage non-small cell lung cancer (NSCLC). Results from the Phase III CheckMate 77T study were presented today at the 2023 European Society for Medical Oncology (ESMO) Congress by researchers from The University of Texas MD Anderson Cancer Center.

    At a median follow-up of 25.4 months, the median EFS with chemotherapy alone was 18.4 months, while the median had not yet been reached for patients receiving perioperative nivolumab, meaning EFS was prolonged significantly over the control group. These results correspond to a 42% reduction in risk of disease progression, recurrence, or death for those receiving the perioperative combination.

    Patients who received the perioperative nivolumab-based regimen also saw significantly higher rates of pathological complete response (pCR), defined as no tumor remaining at surgery, compared with those who received chemotherapy alone (25.3% vs. 4.7%). Rates of major pathological response (MPR), less than or equal to 10% of viable tumor cells remaining at time of surgery, were also higher in patients who received perioperative immunotherapy (35.4% vs. 12.1%).

    “This study builds on the standard-of-care neoadjuvant treatment and supports perioperative nivolumab as an effective approach that reduces the risk of lung cancer relapse,” said principal investigator Tina Cascone, M.D., Ph.D., associate professor of Thoracic/Head & Neck Medical Oncology. “These findings add to evidence that the perioperative immunotherapy path gives patients with operable lung cancer an opportunity to live longer without their cancer returning.”

    Roughly 30% of patients diagnosed with NSCLC have operable disease, meaning their tumor can be removed by a surgical operation. While many of these patients can be potentially cured by surgery, more than half will experience cancer recurrence without additional therapy. Chemotherapy given either before or after surgery provides only a minimal survival benefit.

    The randomized, double-blind CheckMate 77T trial, which began in 2019, included more than 450 NSCLC patients over the age of 18 from around the globe. Participants were randomized to treatment with either neoadjuvant nivolumab with chemotherapy followed by surgery and adjuvant nivolumab, or neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo

    The data showed no new safety signals with the perioperative nivolumab regimen and is consistent with the known safety profiles of individual agents. Grade 3-4 treatment-related side effects were observed in 32% and 25% of patients receiving the perioperative combination or control therapy, respectively. Surgery-related adverse events occurred in 12% of patients in both treatment arms.

    These findings add to recent success seen with neoadjuvant nivolumab plus chemotherapy in NSCLC. In March 2022, the Phase III CheckMate 816 study led to FDA approval of nivolumab combined with platinum-based chemotherapy.

    “I am enthusiastic about the initial findings of the study,” Cascone said. “Looking ahead, it will be critical to identify patient and disease characteristics that will tell us who can potentially be cured with neoadjuvant immunotherapy only and who will benefit from more intensified treatment strategies.”

    The CheckMate 77T study was sponsored by Bristol Myers Squibb. A full list of co-authors and author disclosures can be found here.

    Read this press release on the MD Anderson Newsroom. 

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  • Jennifer Wargo, M.D., elected to the National Academy of Medicine

    Jennifer Wargo, M.D., elected to the National Academy of Medicine

    Newswise — HOUSTON ― Jennifer Wargo, M.D., professor of Surgical Oncology and Genomic Medicine at The University of Texas MD Anderson Cancer Center, has been elected to the National Academy of Medicine (NAM) for her contributions to the understanding of melanoma treatment response and resistance to cancer therapies, including groundbreaking discoveries that reveal how the gut microbiome influences responses to immunotherapy.

    Established originally as the Institute of Medicine in 1970 by the National Academy of Sciences, NAM advises the nation on issues related to health, medicine, health policy and biomedical sciences. Each year, members are elected to the NAM by their peers in recognition of outstanding professional achievement and commitment to service. It is considered one of the highest honors in the fields of health and medicine.

    “I am honored and humbled to be chosen by my peers for inclusion in such a prestigious group of clinicians and scientists,” Wargo said. “We are only beginning to understand the potential for targeting the microbiome to improve treatment outcomes, and I look forward to the discoveries ahead as we seek to better treat, intercept and prevent cancer.”

    Together with her team, Wargo led pioneering research demonstrating that patients with metastatic melanoma who had more diverse gut microbiome populations or an abundance of certain bacterial species had improved clinical outcomes with immune checkpoint inhibitors. This research was published in Science.

    Subsequent research by Wargo and her colleagues discovered how changes to the microbiome can improve outcomes following immunotherapy treatment. Another study published in Science demonstrated that a high-fiber diet was associated with improved responses to immunotherapy in patients with melanoma. These results inspired an ongoing MD Anderson trial, led by Carrie Daniel-MacDougall, Ph.D., and Jennifer McQuade, M.D., evaluating the impact of a high-fiber diet on the microbiome and immunotherapy responses in patients with melanoma and other cancers.

    “Dr. Wargo is a renowned physician-scientist who is passionate about leading breakthrough research that can improve the lives of patients with cancer,” said Peter WT Pisters, M.D., president of MD Anderson. “She has made fundamental and practice-changing contributions to the field, and we congratulate her on this well-deserved honor.”

    Wargo has devoted her career to uncovering the mechanisms responsible for regulating response or resistance to cancer therapies, including targeted therapies and immunotherapies. In previous research, she discovered that treatment with molecularly targeted therapy could sensitize tumor cells to treatment with immunotherapy, suggesting that combining targeted therapy and immunotherapy could improve patient outcomes.

    She joined MD Anderson in 2013 to help lead the Melanoma Moon Shot® and to continue translational research on targeted therapy, immunotherapy and the impact of the gut and tumor microbiome in cancer. Wargo leads MD Anderson’s Platform for Innovative Microbiome and Translational Research (PRIME-TR) to advance novel microbiome-targeted therapeutic approaches. She also is a core member of the James P. Allison Institute at MD Anderson.

    Wargo has authored and co-authored more than 200 articles in peer-reviewed journals and serves in several leadership roles at MD Anderson and in professional societies. She has mentored many young scientists in the field, including those who are part of a Woman in Cancer in Immunotherapy group. Her leadership has been acknowledged through prestigious awards, including the 2023 Edith and Peter O’Donnell Award in Medicine from the Texas Academy of Medicine, Engineering, Science and Technology; the Rising STARs Award from University of Texas System; The Regents’ Health Research Scholars Award from UT System; and the Young Investigator Award from the Society for Melanoma Research (2014). 

    Wargo joins 11 additional MD Anderson clinicians and scientists in the NAM, including current members Jim Allison, Ph.D., Ronald DePinho, M.D., Maura Gillison, M.D., Ph.D., Ellen Gritz, Ph.D., V. Craig Jordan, Ph.D., Guillermina Lozano, Ph.D., David Piwnica-Worms, M.D., Ph.D., Helen Piwnica-Worms, Ph.D., and Anil Sood, M.D. Former members, now deceased, include Waun Ki Hong, M.D., and John Mendelsohn, M.D.

    Read this press release in the MD Anderson Newsroom.

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  • Intensity-modulated radiation therapy provides long-term benefits to patients with locally advanced lung cancer

    Intensity-modulated radiation therapy provides long-term benefits to patients with locally advanced lung cancer

    Newswise — SINGAPORE ― Intensity-modulated radiation therapy (IMRT) should be the preferred choice when treating patients with locally advanced non-small cell lung cancer (NSCLC), as it reduces radiation exposure to the heart and lungs, according to researchers at The University of Texas MD Anderson Cancer Center.  

    Results from a long-term secondary analysis of the NRG Oncology-RTOG 0617 Phase III study, with a median follow-up of 5.2 years, revealed that patients receiving IMRT had a more than two-fold reduction in severe lung inflammation (pneumonitis) compared to those who received 3D-conformal radiotherapy (3D-CRT), 3.5% versus 8.2%.  

    The findings were presented today at the at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer by Stephen Chun, M.D., associate professor of Radiation Oncology.  

    “IMRT spared more normal tissue than 3D-CRT, which translated into a clinically meaningful benefit to patients,” Chun said. “Despite historical concerns of IMRT generating a low-dose radiation bath to a large area of normal lung tissue, we found no excess cancers, increased adverse events or survival detriment over the long term related to this approach.” 

    For decades, 3D-CRT has been the standard of care for locally advanced lung cancer when surgery is not an option. However, it is less precise than IMRT, which sculpts and molds radiation beams to tumor targets, reducing radiation exposure to certain organs.  

    The NRG Oncology-RTOG 0617 study enrolled 482 NSCLC patients from 2007 to 2011 and compared a high dose of radiation (74 Gy) to a standard dose (60 Gy). All patients underwent concurrent chemotherapy (carboplatin/paclitaxel, with or without cetuximab) and either 3D-CRT (53%) or IMRT (47%). 

    Although patients treated with both techniques had similar survival rates, closer inspection of the data demonstrated a correlation between survival and radiation exposure to the heart. IMRT treatment plans achieved significantly lower cardiac radiation doses.  

    Both the 3D-CRT and IMRT groups had similar rates of new cancer development over time. Scientists also saw no evidence that age impacted survival, meaning that age is no reason to exclude elderly patients from curative-intent chemoradiation for locally advanced NSCLC.  

    “The data from our study makes a compelling argument that we should use IMRT for locally advanced lung cancer. As a randomized clinical trial comparing 3D-CRT and IMRT is unlikely to be performed, this study represents the strongest prospective evidence we will ever have in support of IMRT,” Chun said. 

    This trial was funded by the National Cancer Institute (R50CA275822, U10CA21661, U10CA180868, and U10CA180822), Bristol Myers Squibb and Eli Lilly and Company. Chun reports financial relationships with Curio Science, Norton Healthcare, AstraZeneca, Binaytara Foundation, Henry Ford Health, Hong Kong Precision Oncology, ViewRay, the American Board of Radiology and the Japanese Society for Radiation Oncology. A full list of collaborating authors can be found with the abstract here.  

    University of Texas MD Anderson Cancer Center

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  • MD Anderson and Panacea launch Manaolana Oncology to develop antibody-based therapies for cancer

    MD Anderson and Panacea launch Manaolana Oncology to develop antibody-based therapies for cancer

    Newswise — HOUSTON and SAN MATEO, Calif. ― The University of Texas MD Anderson Cancer Center and Panacea Venture today announced the launch of Manaolana Oncology Inc., a new company created to develop and advance antibody-based therapies against novel cancer antigens.

    Manaolana Oncology seeks to build upon the innovative antibody production capabilities and intellectual property of MD Anderson to research and develop novel monoclonal antibodies (mAbs) and other antibody-based therapies for a variety of cancer types, with the goal of advancing promising therapies into clinical studies at MD Anderson.

    The company will be headquartered in Thousand Oaks, Calif., and will be led by an executive team with more than 100 years of combined experience in product development and strategic partnering. Panacea will fund start-up expenses for Manaolana Oncology and will support the recruitment of additional experienced executives to shape the company.

    “By developing therapies targeting new tumor antigens, Manaolana Oncology aims to address a critical need for patients with cancer. Manaolana is the Hawaiian word for hope, and it is our intent to offer patients renewed hope against this disease,” said Winson Tang, M.D., co-founder of Manaolana Oncology. “Manaolana Oncology brings together MD Anderson’s expert scientists and clinicians with Panacea’s experienced biotechnology team to create a focused organization working to develop a novel portfolio of monoclonal antibodies.”

    Monoclonal antibody therapies have emerged as important treatment options for many types of cancer. They are designed to recognize and bind to specific targets, or antigens, on cancer cells in order to manipulate certain signaling pathways or recruit immune cells to the tumor.

    The laboratory of Samir Hanash, M.D., Ph.D., professor of Clinical Cancer Prevention at MD Anderson, has conducted an extensive characterization of the cancer surfaceome, resulting in a comprehensive catalogue of proteins found specifically on the surface of cancer cells across tumor types.

    “By combing through petabytes of proteomic data, our team has uncovered many cancer-restricted antigens that may offer prime targets for monoclonal antibody therapies,” Hanash said. “We look forward to collaborating with Manaolana Oncology to develop novel antibody-based therapeutics that offer patients impactful new treatment options.”

    Kevin McBride, Ph.D., associate professor of Epigenetics and Molecular Carcinogenesis at MD Anderson, has pioneered a high-throughput platform to clone and produce mAbs from isolated B cells, enabling  the development of highly specific antibodies against a particular cell surface target to create novel therapeutic mAbs.

    “This is an important evolution because current approaches to creating high-quality monoclonal antibodies require lengthy and intensive production protocols, which can be costly and are not always successful,” McBride said. “We look forward to working with Manaolana Oncology to build on these techniques and rapidly bring forward innovative therapies for clinical evaluation.”

    Manaolana Oncology intends to optimize the techniques developed at MD Anderson in order to improve the speed and efficiency in of producing antibodies against promising candidate antigens.

    Read this press release in the MD Anderson Newsroom.

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    Disclosure

    MD Anderson has an institutional conflict of interest (COI) with Panacea and Manaolana Oncology due to MD Anderson’s ownership interest in Manaolana and the future research to be conducted at MD Anderson. These relationships will be managed according to an MD Anderson Institutional COI Management and Monitoring Plan.

    About Panacea Venture

    Panacea Venture is a life sciences venture capital firm with global vision and presence across three continents. The firm was founded in 2017 and is currently managing four funds investing in early-stage companies through public investments. Panacea incubates early-stage companies with breakthrough technologies and discoveries that can potentially address unmet medical needs to enhance quality of life on a global scale. The investment team has more than 100 years of combined investing experience and, along with venture partners and advisors, provides broad coverage across emerging and established biotech, diagnostic and medtech sectors. In addition, Panacea’s highly experienced team has a strong track record navigating portfolio companies to success. 

    About MD Anderson

    The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world, and, in 1971, it became one of the nation’s first National Cancer Institute (NCI)-designated comprehensive cancer centers. MD Anderson is No. 1 for cancer in U.S. News & World Report’s “Best Hospitals” rankings and has been named one of the nation’s top two hospitals for cancer since the rankings began in 1990. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672).

     

    University of Texas MD Anderson Cancer Center

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  • Blood test aids in predicting lung cancer mortality risk

    Blood test aids in predicting lung cancer mortality risk

    Newswise — HOUSTON ― A blood-based test developed by researchers at The University of Texas MD Anderson Cancer Center can predict an individual’s risk of dying from lung cancer when combined with a personalized risk model.

    According to new data published today in the Journal of Clinical Oncology, a blood-based four-protein panel (4MP), when combined with a lung cancer risk model (PLCOm2012), can better identify those at high risk of dying from lung cancer than the current U.S. Preventive Services Task Force (USPSTF) criteria.

    These findings build upon previous MD Anderson research demonstrating the combination test more accurately determined who is likely to benefit from lung cancer screening than the USPSTF criteria.

    “This simple blood test has the potential to save lives by determining the need for lung cancer screening on a personalized basis,” said co-corresponding author Samir Hanash, M.D., Ph.D., professor of Clinical Cancer Prevention. “Given the challenges associated with CT as a frontline screening method for lung cancer and the fact that most individuals diagnosed with the disease do not meet current guidelines, there is an urgent demand for an alternative approach.”

    For this study, MD Anderson researchers analyzed pre-diagnostic blood samples from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, including 552 individuals who later developed lung cancer and 2,193 who did not. Of the 552 individuals diagnosed during the six-year study period, 70% (387) died from lung cancer.

    Using hazard ratios, the researchers assessed the relationship between the risk scores generated by the combination model (4MP + PLCOm2012) and the incidence of lung cancer death. The combination showed improved sensitivity, specificity and positive predictive value compared to the 2013 and 2021 USPSTF criteria for predicting lung cancer-specific mortality among individuals who smoked at least 10 pack-years (PYs).

    The USPSTF recommends that adults at elevated risk for lung cancer receive a low-dose CT scan each year, which was shown to reduce lung cancer deaths in the 2011 National Lung Screening Trial (NLST). The 2021 USPSTF criteria applies to adults aged 50 to 80 who have at least a 20 PY smoking history and currently smoke or have quit within the past 15 years.

    “For individuals who currently are not eligible for lung cancer screening, a positive test may help to identify those possibly at risk for lung cancer death,” said co-corresponding author Edwin Ostrin, M.D., Ph.D., assistant professor of General Internal Medicine. “We envision this as a tool that could be deployed worldwide, as the future of early detection of this disease.”

    Lung cancer causes an estimated 25% of cancer deaths. Early detection improves prospects of survival, but most countries do not screen for it. Fewer than half of all U.S. cases are among people who are eligible under USPSTF guidelines.

    While the blood test could be implemented as a lab-developed test in the near future, Food and Drug Administration (FDA) approval likely would require evaluation through a prospective clinical trial.

    Hanash is an inventor on a patent application related to the blood test. A complete list of co-authors and their disclosures is included in the paper.

    This study was supported by the National Institutes of Health and National Cancer Institute (U01CA194733, U01CA213285, U01CA200468, U24CA086368), the Cancer Prevention & Research Institute of Texas, Lyda Hill Philanthropies, and the Lung Cancer Moon Shot®, part of MD Anderson’s Moon Shots Program®.

    Read the full release on the MD Anderson Newsroom. 

     

    University of Texas MD Anderson Cancer Center

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  • ASCO: Targeted therapy induces responses in HER2-amplified biliary tract cancer

    ASCO: Targeted therapy induces responses in HER2-amplified biliary tract cancer

    ABSTRACT: 4008

    Newswise — CHICAGO ― HER2-targeted bispecific antibody zanidatamab demonstrated durable responses in patients with treatment-refractory HER2-positive biliary tract cancer (BTC), researchers from The University of Texas MD Anderson Cancer Center reported at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The study results also were published today in The Lancet Oncology.

    In the first cohort of the global Phase II HERIZON-BTC-01 trial, which included 80 patients with HER2-positive tumors, the confirmed objective response rate (cORR) was 41% with a median duration of response (DOR) of 12.9 months at a median follow-up of 12.4 months. Among the 33 responders, 49% had ongoing responses and 82% had a response lasting more than 16 weeks. This is the largest study of a HER2-targeted drug in BTC.

    “Chemotherapy for patients with biliary tract cancers who have progressed on first-line therapy is usually associated with a 5% response rate,” said global trial lead Shubham Pant, M.D., professor of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics. “These results provide evidence that zanidatamab can achieve durable responses and may offer a new treatment opportunity for patients who previously had limited options.”

    Patients with advanced BTC who progress after first-line treatment are offered standard-of-care therapies with limited clinical benefit and only modest improvement in survival. HER2-targeted therapies have improved survival in HER2-positive breast and gastric cancers, but there currently is no approved HER2-targeted therapy for BTC.

    Zanidatamab was first evaluated in a Phase I trial led by Funda Meric-Bernstam, M.D., chair of Investigational Cancer Therapeutics. The trial results supported HER2 as an actionable target in various cancer types, including biliary tract cancer. Based on those results, MD Anderson researchers advanced zanidatamab into this Phase II trial for patients with BTC.

    Biliary tract cancer, also known as cholangiocarcinoma, develops in the bile ducts, a series of thin tubes that run from the liver to the small intestine. There are three different types of BTC, whose names are based on the location where the cancer forms. According to the American Cancer Society, around 8,000 people in the U.S. are diagnosed each year with BTC. However, the true count likely is higher because these cancers can be hard to diagnose and are often misclassified, Pant explained. The five-year survival rate for metastatic BTC is less than 5%, highlighting an urgent need for new treatments.

    This open-label, single-arm trial evaluated the anti-tumor activity of zanidatamab in patients with HER2-amplified advanced BTC, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. The trial was conducted at 67 sites; patients were divided into two cohorts based on HER2 expression (positive or low/negative) by tumor immunohistochemistry. The primary endpoint was cORR in the HER2-positive cohort.

    The study enrolled 80 patients in the HER2-positive cohort and seven patients in the HER2-low/negative cohort. All patients had received one previous line of gemcitabine-containing therapy. The median age was 64 years and patients were 65.5% Asian, 28.7% white and 5.7% other. Of the trial participants, 52% had gallbladder cancer, 30% had intrahepatic cholangiocarcinoma, and 18% had extrahepatic cholangiocarcinoma.

    There were no responses to zanidatamab observed in the HER2-low/negative cohort. Across both cohorts, grade 3 treatment-related adverse events occurred in 18% of patients. Two patients (2.3%) discontinued zanidatamab due to an adverse event. No grade 4 or 5 treatment-related adverse events were reported.

    “Given this data, we believe strongly that there should be continued efforts to explore zanidatamab as a viable treatment option for HER2-positive biliary tract cancer,” Pant said. “We are encouraged by the potential impact of zanidatamab on improving patient outcomes.”

    Pant and his team still are evaluating progression-free survival and overall survival in these patients. Additionally, clinical trials are underway to further investigate the therapeutic potential of zanidatamab as a monotherapy and in combination with first-line chemotherapy for HER2-positive BTC.

    This study was funded by Zymeworks BC Inc. and BeiGene Ltd. Pant has worked in a consulting/advisory role for and received research support from Zymeworks. A full list of co-authors and their disclosures can be found here.

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    University of Texas MD Anderson Cancer Center

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  • Pan-cancer T cell atlas reveals new details of tumor microenvironment

    Pan-cancer T cell atlas reveals new details of tumor microenvironment

    Newswise — HOUSTON ― A new study led by researchers at The University of Texas MD Anderson Cancer Center, published today in Nature Medicine, provides a deeper understanding of the vast diversity of T cell states as well as their relationships and roles within the complex tumor microenvironment, bringing a fresh perspective to understanding immunotherapy efficacy in cancer.

    Recent studies have shown that the phenotypic states of T cells, as well as their relative proportions, play a crucial role in determining the effectiveness of immunotherapy and the likelihood of potential adverse effects. This new pan-cancer single-cell T cell atlas integrates 27 single-cell RNA sequencing datasets, including nine unique datasets from MD Anderson, covering 16 cancer types. It is the most detailed picture to date of the heterogeneity of T cells present within the tumor microenvironment.

    “This kind of large dataset and comprehensive pan-cancer analysis provides the opportunity to see things that aren’t visible when studying a single type of cancer or even a handful of cancer types,” said corresponding author Linghua Wang, M.D., Ph.D. associate professor of Genomic Medicine. “We hope these high-resolution maps, including the thoroughly characterized T cell states, are valuable resources for facilitating future T cell studies and biomarker discovery.”

    One notable discovery from this study is the previously undescribed T cell stress response state, or TSTR. In prior single-cell studies, these T cells often were overlooked or considered to be artifacts related to tissue dissociation. However, with the extensive data available, the researchers were able to identify these cells as a clearly unique group, distinct from other CD4+ or CD8+ T cell subsets, and to validate their existence in situ using multiple spatial profiling methods.

    TSTR cells can be thought of as ‘stressed out’ T cells and, just like a stressed person might be less effective at their job, they seem to be less effective at fighting cancer. While both TSTR cells and exhausted T cells may be dysfunctional, TSTR cells appear to follow a unique differentiation path, distinct from the trajectory of exhausted T cells.

    TSTR cells are characterized by high heat shock gene expression and, importantly, are seen at significantly higher fractions in both CD4+ and CD8+ T cells following immune checkpoint blockade therapy, particularly in non-responders. This suggests TSTR cells may play a role in resistance to immunotherapy. This new T cell state adds an additional layer to our understanding of the intricate biology of cancer and provides a potential target for future therapies.

    “The fact that these TSTR cells are found in many different types of tumors opens up a whole new world of possibilities that could have high translational potential,” Wang said. “Investigating the mechanistic causes of stress response in T cells, understanding how these stressed T cells are induced in the tumor microenvironment, and learning how to stop or reverse this TSTR state could catalyze the development of more effective therapeutic strategies that may bring the benefit of immunotherapy to more cancer patients.”

    This work also underscores the value of large, integrative datasets in oncology. This pan-cancer T cell atlas exemplifies the power of big data to unravel the complex landscape of T cells within tumors. The researchers described a total of 32 T cell states in this study, and further identified seven subpopulations within the CD4+ regulatory subset, five within the CD4+ follicular helper T cell population, and eight states among proliferating T cells.

    These findings all highlight the extensive heterogeneity of T cell states within the tumor microenvironment and the need to further understand how these states contribute to disease progression and immunotherapy response.

    “There are still many questions left to answer,” Wang said. “One of the limitations of this study is we don’t have the corresponding T cell receptor data for most of the datasets analyzed. We are not sure what triggers the TSTR state, and we don’t know from which T cell subset(s) they originate. It also is unclear whether these TSTR cells are specific to tumor cells and how they communicate with and influence other cells within the tumor microenvironment.”

    The research team has shared their T cell atlas with the wider research community through the Single-Cell Research Portal, a user-friendly, interactive web portal. This portal, developed by the team, allows both internal and external users to visualize and query the atlas without the need for bioinformatics skills.

    The team has also developed a tool named TCellMap, which enables researchers to automatically annotate T cells from their datasets by aligning with the high-resolution T cell maps generated by this study. Wang expressed her hope that these resources will prove valuable to scientists aiming to perform an in-depth analysis of T cells, leading to further discoveries and ultimately enhancing strategies for T cell therapy.

    Dr. Yanshuo Chu, Ph.D., from the Wang laboratory led the data analysis. This research was supported by MD Anderson, the National Institutes of Health/National Cancer Institute (R01CA266280, U01CA264583, P50CA016672, T32CA217789), the Cancer Prevention and Research Institute of Texas (CPRIT) and the U.S. Department of Defense. A full list of collaborating authors and their disclosures can be found with the full paper here.

    University of Texas MD Anderson Cancer Center

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  • ASCO: Luspatercept enables majority of patients with MDS to end reliance on blood transfusions

    ASCO: Luspatercept enables majority of patients with MDS to end reliance on blood transfusions

    ABSTRACT: 7003

    Treatment with luspatercept improved red blood cell counts and erythroid responses compared to treatment with epoetin alfa in patients with myelodysplastic syndromes (MDS), allowing the majority to no longer require regular blood transfusions. Results from the Phase III COMMANDS trial, led by researchers at The University of Texas MD Anderson Cancer Center, were reported at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

    The study evaluated the efficacy and safety of first-line treatment with luspatercept, which enhances red blood cell maturation, compared with epoetin alfa, a therapy commonly used for low blood cell count, in transfusion-dependent patients with anemia due to very low- to intermediate-risk MDS.

    In this interim analysis, 58.5% of patients receiving luspatercept achieved the primary endpoint of independence from red blood cell transfusions compared to 31.2% of patients who received epoetin alfa. Within the first 24 weeks of treatment transfusion, 47.6% of luspatercept patients achieved transfusion independence versus 29.2% of patients receiving epoetin alfa. Additionally, 74.1% of patients who received luspatercept saw hematologic improvement in erythroid responses greater than eight weeks, compared to 51.3% of patients who received epoetin alfa.

    “Patients with myelodysplastic syndromes often experience anemia that requires frequent red blood cell transfusions,” said Guillermo Garcia-Manero, M.D., professor of Leukemia and lead investigator of the study. “In this study, we observed a significant improvement in patient red blood cell counts with luspatercept, representing a promising advance to enhance the lives of these patients.” 

    Myelodysplastic syndromes are a group of diseases in which the bone marrow doesn’t produce enough healthy blood cells, including red blood cells. Patients with MDS often experience symptoms such as anemia, fatigue, shortness of breath and increased vulnerability to infection.

    Because of the frequency of anemia, most patients require regular red blood cell transfusions. Some cases of MDS can progress to acute myeloid leukemia (AML). Luspatercept is a novel agent that enables late-stage red blood cell maturation. By targeting the TGF-β signaling pathway, luspatercept helps restore normal red blood cell creation.

    The trial enrolled 301 patients at 226 sites. Patients were randomized to receive subcutaneous luspatercept every three weeks or subcutaneous epoetin alfa weekly for 24 weeks. Patient characteristics were balanced across both treatment arms.

    Treatment-related adverse events of all grades occurred in 30.3% of patients in the luspatercept group and 17.6% in the epoetin alfa group. Eight patients (4.5%) that received luspatercept discontinued treatment due to treatment-related adverse events. AML progression was reported in four patients receiving luspatercept and five patients receiving epoetin alfa. The safety profile was consistent with previous studies of the drug.

    “These results show, for the first time, superior effectiveness of an innovative therapy over epoetin alfa,” Garcia-Manero said. “I am encouraged by these results, as luspatercept represents a transformative therapy that could become a new standard of care for patients with transfusion-dependent myelodysplastic syndromes.”

    The patients in this study continue to be followed long term to determine overall survival, time of transfusion independence and frequency of progression to AML.

    The study was funded by Bristol Myers Squibb. Garcia-Manero has worked in a consulting/advisory role for and received research support from Bristol Myers Squibb. A full list of co-authors and disclosures can be found here.

    University of Texas MD Anderson Cancer Center

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  • MD Anderson Research Highlights for May 24, 2023

    MD Anderson Research Highlights for May 24, 2023

    Newswise — HOUSTON ― The University of Texas MD Anderson Cancer Center’s Research Highlights showcases the latest breakthroughs in cancer care, research and prevention. These advances are made possible through seamless collaboration between MD Anderson’s world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back.

    Recent developments include a new treatment option for relapsed/refractory mantle cell lymphoma, a better understanding of protein variants that trigger tumor cell death and activate antitumor immunity, insights into the relationship between sickle cell trait and renal medullary carcinoma, clearer awareness of the clinical relevance of CD8 T cell state in acute myeloid leukemia, and an understanding of the distinct neuronal pathways triggered by chemotherapy and nerve injury. 

    Phase I/II trial shows safety and efficacy of pirtobrutinib in advanced MCL
    Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) – an aggressive subtype of B-cell non-Hodgkin lymphoma – initially respond well to covalent Bruton tyrosine kinase inhibitors (cBTKis) but eventually develop resistance, underscoring the need for more effective therapeutic strategies. Pirtobrutinib – a highly selective non-covalent BTKi – inhibits both normal and mutant BTK, providing a potential alternative. In a first-in-human Phase I/II clinical trial, researchers led by Michael Wang, M.D., examined the safety and efficacy of pirtobrutinib monotherapy in 90 patients with R/R MCL who previously received cBTKi treatment. The objective response rate was 57.8%, including 20% with complete responses, and the 12-month estimated duration of response rate was 57.1%. The most common side effects were fatigue, diarrhea and dyspnea. Grade 3 adverse events were infrequent and only 3% of patients discontinued treatment. The study demonstrated that pirtobrutinib was safe and showed durable efficacy in R/R MCL. Based on this data, the Food and Drug Administration granted accelerated approval for pirtobrutinib in R/R MCL in Jan. 2023. Learn more in the Journal of Clinical Oncology.

    Specific protein variants trigger cancer cell death and improve antitumor response
    The gasdermin B (GSDMB) protein can trigger cancer-associated pyroptosis – a form of programmed cell death that activates antitumor immune responses – but its exact role is controversial. The protein has multiple variants created from mRNA splicing, and these can have either anti- or pro-tumor functions. In this study, researchers led by Qing Kong, Ph.D., and Zhibin Zhang, Ph.D., examined six GSDMB splicing variants to provide insights into which are involved in pyroptosis. Relative to other variants, isoforms 3/4 were cytotoxic for tumor cells, triggering pyroptosis and resulting in better antitumor outcomes in bladder and cervical cancer models. The study suggests that tumors may be preferentially generating non-cytotoxic GSDMB variants in order to protect against pyroptosis. It also highlights the potential for therapeutic strategies that can increase production of cytotoxic GSDMB variants to improve antitumor immunity and enhance immunotherapy response. Learn more in Science Immunology. 

    Link between sickle cell trait and SMARCB1 loss observed in renal medullary carcinoma
    Renal medullary carcinoma (RMC) is a rare and aggressive form of kidney cancer that typically develops in young adults with sickle cell trait (SCT). Loss of the SMARCB1 tumor suppressor is a defining characteristic of RMC tumors. To better understand the mechanisms driving RMC and to improve treatment options, researchers led by Giannicola Genovese, M.D., Ph.D., Pavlos Msaouel M.D., Ph.D., and Melinda Soeung, Ph.D., investigated whether the loss of SMARCB1 provides a survival advantage in the presence of SCT. They demonstrated that a lack of oxygen induced by SCT leads to SMARCB1 degradation, protecting cells from hypoxic stress. The results suggest that SMARCB1 loss improves the survival of RMC cells under hypoxia, potentially explaining why SMARCB1-deficient tumors are resistant to therapeutic agents targeting hypoxia pathways. These insights may help researchers develop more effective treatments against RMC. Learn more in Proceedings of the National Academy of Sciences.

    CD8 T Cells in AML display continuous differentiation and clonal hyperexpansion
    Limited research is available on CD8 T cell exhaustion in hematologic cancers, specifically acute myeloid leukemia (AML). In a study led by Hussein Abbas, M.D, Ph.D., researchers characterized CD8 T cells from healthy donors as well as newly diagnosed (NewlyDx) and relapsed/refractory (R/R) AML patients. They discovered very few “exhausted” cells, with effector CD8 T cells from NewlyDx and R/R patients having different cytokine and metabolic profiles than the classic exhaustion signature seen in solid tumors. Researchers refined a 25-gene signature associated with poor outcomes in previously untreated AML patients, suggesting that the CD8 cell state may be clinically relevant. Analysis of T cell receptor sequencing data also revealed an increase in clonal hyperexpansion in R/R patient cells. The study highlights shared characteristics between CD8 cells in AML and those in solid cancer, suggesting that immune-based therapy in AML is likely to be most successful in earlier stages when CD8 T cells can afford plasticity. Learn more in Cancer Immunology Research.

    Chemotherapy and nerve injury induces chronic pain via different sensory neurons
    Treatment with chemotherapy is necessary for many patients with cancer, but it can sometimes cause chronic pain similar to traumatic nerve injuries. Studies have shown chemotherapy-induced neuropathy augments glutamate NMDA receptor (NMDAR) activity in the spinal cord, but little is known about the pathways involved. Researchers led by Yuying Huang, Ph.D., Shao Rui-Chen, M.D., and Hui-Lin Pan, M.D., Ph.D., found that chemotherapy triggers NMDAR activity in specific excitatory neurons. Removing NMDAR from these primary sensory neurons diminished chemotherapy-induced pain in laboratory models. Alternatively, chronic pain from traumatic nerve injury mainly resulted from the NMDAR expressed in different spinal neurons. The results suggest that chronic pain following nerve injury and chemotherapy is triggered by the NMDAR in different neurons and pathways, highlighting potential cellular targets to help treat these separate conditions. Learn more in The Journal of Neuroscience.  

    In case you missed it
    Read below to catch up on recent MD Anderson press releases.

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    University of Texas MD Anderson Cancer Center

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