Latest news with #CityofHope
Medscape
3 days ago
- Business
- Medscape
Ph+ALL: Post-Induction, Ponatinib Yields Molecular Response
In the treatment of newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), patients who fail to achieve initial molecular response with the third-generation tyrosine kinase inhibitor (TKI) ponatinib following induction can nevertheless go on to achieve minimal residual disease (MRD) negativity — and at higher rates than the earlier generation TKI imatinib. 'These results support the clinical benefit and tolerability of continuing ponatinib beyond cycle 3 in patients with newly diagnosed, Ph-positive ALL who do not achieve MRD-negativity by the end of induction,' first author Ibrahim Aldoss, MD, of City of Hope hospital in Duarte, California, told Medscape Medical News . The study was presented this week at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Ph+ ALL, the most common subtype of adult ALL and once associated with a particularly poor prognosis, has seen significantly improved outcomes with TKIs in combination with chemotherapy or steroids. However, even with the third generation of TKIs representing the standard of care, relapses can occur due to variant-acquired resistance, particularly T315I. Ponatinib was designed to address that challenge, effectively inhibiting BCR-ABL1 with or without any single-mutation variants, including T315I. The previous global, phase 3, open-label PhALLCON trial represented the first head-to-head comparison of ponatinib (30 mg/day) with the first-generation imatinib (600 mg/day), along with reduced-intensity chemotherapy followed by monotherapy of either drug until disease progression or unacceptable toxicity. The trial met its primary endpoint of no sign of molecular disease (MRD-negative complete response), which correlates with long-term outcomes, by the end of cycle 3 of induction, with ponatinib showing a significantly higher rate vs imatinib (34.4% vs 16.7%; P = .002), and comparable safety outcomes. Current Post-Hoc Analysis To investigate the key question of the effects of further treatment among the majority of patients who did not achieve MRD negativity by the end of induction, or 3 cycles of low-density chemotherapy, Aldoss and colleagues conducted the current post-hoc analysis of 113 patients (73 receiving ponatinib, 40 imatinib) who continued treatment following the end of induction, Of those patients, 48% in the ponatinib group (n = 35) and 33% with imatinib (n = 13) did achieve MRD negativity after induction cycle 4, day 1. The median duration of MRD negativity was not reached with ponatinib compared with 3.8 months with imatinib treatment. Overall, 16 patients (10 receiving ponatinib, 6 imatinib) went on to have a hematopoietic stem cell transplant (HSCT). Among 140 patients who did not achieve MRD negativity by the end of induction, the median event-free survival was not reached with ponatinib therapy compared with 24.8 months with imatinib. The 2-year rates of event-free survival in the two groups were 82% and 62%, respectively. The rates of treatment-emergent adverse events (TEAEs) were similar in the patients who had not achieved MRD negativity by the end of induction, at 100% with ponatinib and 98% imatinib. In addition, 71% and 54% of patients, respectively, had a dose modification (discontinuation, reduction, or interruption) due to TEAEs. Of the 48 patients with MRD negativity after cycle 4, day 1, 100% of patients in each treatment group had TEAEs, and 69% and 62% had dose modification due to TEAEs. Vascular Toxicities Avoided With Lower Dose While ponatinib has previously been associated with increased vascular toxicity and arterial occlusive events, particularly among patients receiving higher doses for longer periods, those events were rare in the current study and not significantly different between the two arms, Aldoss said. He added that the improvement is likely the result of a lowering of the initial dose in the PhALLCON study to 30 mg/day compared with the prior use of 45 mg/day — and a further reduction to 15 mg/day after induction likely helped reduce those effects. 'We feel that using a more optimized, safer lower dose was actually the reason why we're seeing comparable safety and lower arterial occlusive events in this study,' Aldoss said. The benefits were observed across the evaluated subgroups, including patients older than age 60 years, which is important due to previous research showing some increased risk with ponatinib among older adults. Benefits Extend to Older Patients With more stringent criteria in the trial excluding patients with significant cardiovascular disease, Aldoss noted that, 'if anything, the benefit was actually more prominent in patients older than 60.' He therefore recommended consideration of that criteria in making patient selection. Importantly, in the PhALLCON trial, the proportion of patients in the ponatinib arm who went on to receive HSCT was lower compared with imatinib, which could notably benefit older patients who may not respond as well to such treatment. 'The potency of ponatinib in combination with low-dose chemotherapy or no chemotherapy may render HSCT unnecessary for older or frail patients who achieve a 3-month MRD-negative complete remission,' the authors conclude in the study. While the survival estimation can otherwise require long follow-up analysis, MRD negativity is increasingly seen as an important surrogate measure of long-term survival. In one recent meta-analysis, MRD negativity at the end of induction had a significantly greater prognostic value in terms of event-free survival and long-term survival in patients with PH-positive ALL. The current findings suggest such benefits may be achieved even when there is a delay in MRD negativity status after induction, Aldoss noted. 'This analysis supports [the conclusion] that a clinical benefit in event-free survival is observed, even if you don't achieve the MRD negativity at the end of induction,' he said. Following the publication of the PhALLCON trial, the US Food and Drug Administration granted ponatinib accelerated approval for the indication of Ph-positive ALL in March 2024. In an accompanying editorial, Jacqueline S. Garcia, MD, of the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues speculated about the role of ponatinib in the context of other promising options. 'It is unclear whether PhALLCON's ponatinib regimen will be preferred against second-generation tyrosine kinase inhibitors, especially regimens that incorporate blinatumomab or allosteric BCR-ABL1 inhibitors,' they write. Importantly, with long-term data showing durable hematologic and molecular responses with combined dasatinib and blinatumomab, thereby offering a chemotherapy-free and toxicity-sparing induction and consolidation regimen, for instance, the option of ponatinib and reduced-intensity chemotherapy 'may not be the optimal first choice for all Ph+ ALL patients,' they say. A notable limitation of the study was that MRD was not assessed with next-generation sequencing (NGS), Pamela Sung, MD, PhD, an assistant professor in the Departments of Medicine and Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, who co-moderated the ASCO session, told Medscape Medical News . 'NGS is more sensitive and specific than BCR-ABL1 PCR for B-ALL MRD detection,' she said. 'It is increasingly being recognized that multi-lineage or 'CML-like' ALL exists, where patients are MRD-positive by BCR-ABL PCR but negative by NGS.' Such patients have a similar relapse rate to those who are MRD-negative by both measures, but it is not known how many patients experience such discordance, Sung noted. The findings are nevertheless important, not so much in showing the rate of MRD at a certain point in time, but the potential trajectory in MRD over the course of treatment, Sung noted. 'Typically, we would continue the current therapy regimen so long as the MRD is continuing to decrease,' she explained. 'However, if unable to clear at the end of 1 to 2 cycles of consolidation, we would recommend allogeneic transplant if eligible. 'These new data support this strategy, using a high potency TKI with few deaths and relapses in the ponatinib arm (10%) for this subset of patients that were MRD-positive at the end of induction. 'Nearly half of patients converted to MRD-negative by the end of treatment with ponatinib, many of whom were negative at [a deeper molecular response] of MR4.5.' The study was sponsored by Takeda Development Center Americas, Inc.
Yahoo
4 days ago
- Business
- Yahoo
Late-breaking analysis demonstrates characteristics associated with long-term overall survival with Onivyde® regimen in metastatic pancreatic adenocarcinoma
PARIS, France, 31 May 2025 Late-breaking (LBA4175) post-hoc analysis data from the Phase III NAPOLI 3 study were presented today at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. These results found a median overall survival (mOS) of 19.5 months among long-term survivors (n=15) with metastatic pancreatic adenocarcinoma (mPDAC) treated with the Onivyde (irinotecan liposome injection) plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX) regimen as a first-line treatment (n=120), with younger age at diagnosis, and certain tumor and metastasis locations associated with long-term survivorship. Pancreatic adenocarcinoma (PDAC) is the most common type of cancer that forms in the pancreas, with more than 60,000 people diagnosed annually in the U.S. and nearly 500,000 people globally.34 It is often detected after the disease has spread to other parts of the body (metastatic or stage IV)5 and fewer than 20% of people diagnosed with metastatic pancreatic adenocarcinoma (mPDAC) survive longer than one year. Overall, pancreatic cancer has the lowest five-year survival rate of all cancer types globally and in the U.S. 'When people are diagnosed with metastatic pancreatic adenocarcinoma, the most important question remains: how long will they have with their loved ones,' said Dr. Vincent Chung, Medical Oncologist, City of Hope. 'Findings from the NAPOLI 3 post-hoc analysis provide important context on long-term overall survival with the Onivyde (NALIRIFOX) treatment regimen.' The analysis included patients who survived for 18 months or longer (N=15), with findings showing long-term survivors living with mPDAC had a mOS of 19.5 months (interquartile range [IQR]: 18.8–22.6). Clinical and pathological factors of long-term survivors included younger than average age at time of diagnosis (median age 61.0 (IQR: 49.0–70.5) as well as tumor location. Fewer patients had tumors in the head or tail of the pancreas (53.3% had the main pancreatic tumor located in the body of the pancreas), a substantial proportion had liver metastasis (66.7%) and ≥3 metastatic sites (53.3%). Additionally, findings indicate dose reduction and treatment delays resulted in prolonged exposure and higher cumulative doses of the Onivyde (NALIRIFOX) regimen. Liver metastasis and ≥3 metastatic sites, dose modifications and an otherwise good clinical profile enabled people to achieve a long mOS. Consideration should be taken when interpreting these results as a post-hoc analysis with a small sample size. "Data from the Phase III NAPOLI 3 trial were the first positive data of its kind in a decade and continue to reinforce the potential for long-term outcomes with the Onviyde (NALIRIFOX) regimen,' said Sandra Silvestri, MD, PhD, Executive Vice President, Chief Medical Officer, Ipsen. 'With people on average living just 4-6 months following diagnosis with pancreatic adenocarcinoma, these data help us to understand the characteristics associated with long-term survival seen in the NAPOLI trial, an important advancement for this difficult-to-treat cancer where data of this kind are scarce.' ENDS About Onivyde (irinotecan liposome injection)Onivyde is a long-circulating liposomal topoisomerase inhibitor. In Onivyde, irinotecan is enclosed in tiny fat particles called liposomes which accumulate in the tumor and release slowly over time. Onivyde is administered via intravenous infusion over 90 minutes every two weeks with recommendations on dosing modifications. Onivyde, as part of the NALIRIFOX regimen (combined with oxaliplatin, fluorouracil (FU) and leucovorin (LV)), is for people living with mPDAC who are treatment naïve or used in combination with FU and LV following gemcitabine-based therapy. Onivyde is not indicated as a single agent for the treatment of adult patients with metastatic pancreatic adenocarcinoma. Ipsen has exclusive commercialization rights for the current and potential future indications for Onivyde in the U.S. Servier, an independent international pharmaceutical company governed by a foundation and with an international presence in 140 countries, is responsible for the commercialization of Onivyde outside of the U.S., Taiwan and Canada. PharmaEngine is a commercial stage oncology company headquartered in Taipei and is responsible for the commercialization of Onivyde in Taiwan. About NAPOLI 3 Study NAPOLI 3 is a randomized, open-label Phase III trial of an Onivyde treatment regimen (NALIRIFOX) in treatment-naïve mPDAC. NAPOLI 3 enrolled 770 patients across 187 trial site locations in 18 countries across Europe, North America, South America, Asia, and Australia. Patients were randomized to receive Onivyde plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX regimen; n=383) twice in a month (days 1 and 15 of 28-day cycle) compared to an injection of nab-paclitaxel and gemcitabine (n=387) administered three times a month (days 1, 8, 15 of a 28-day cycle). About Ipsen We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries. Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit Ipsen Media contacts Investors Khalid Deojee | +33 666019526 | Media Sally Bain | +1 8573200517 | Anne Liontas | +33 0767347296 | Disclaimers and/or Forward-Looking StatementsThe forward-looking statements, objectives and targets contained herein are based on Ipsen's management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect Ipsen's future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words 'believes', 'anticipates' and 'expects' and similar expressions are intended to identify forward-looking statements, including Ipsen's expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external-growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by Ipsen. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising medicine in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. Ipsen must face or might face competition from generic medicine that might translate into a loss of market share. Furthermore, the research and development process involves several stages each of which involves the substantial risk that Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Ipsen's patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen's activities and financial results. Ipsen cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of Ipsen's partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen's business, financial position or performance. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward-looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen's business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen's latest Universal Registration Document, available on References 1 Wainberg et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-1281.2 Chung et al. NAPOLI 3 phase 3 study of NALIRIFOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): final overall survival (OS) analysis and characteristics of the long-term survivors. As presented at ASCO Congress 2025 Chicago, USA3 American Cancer Society – Cancer Facts and Figures 2024. Available : Orth, M., Metzger, P., Gerum, S. et al. Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiat Oncol 14, 141 (2019). Attachment Ipsen PR_ASCO NAPOLI_31052025
Medscape
19-05-2025
- Health
- Medscape
Cancer's Toll Raises Suicide Risk for Spouses
This transcript has been edited for clarity. Hello. I'm Dr Maurie Markman from City of Hope. I'd like to briefly discuss a very difficult topic, but one that I believe needs to be more openly discussed — not necessarily the specifics of the topic, but the implications of findings. The paper I'm referring to is entitled, 'Suicide attempt and suicide death among spouses of patients with cancer.' This was reported in JAMA Oncology . What we're looking at here in this analysis are data from Denmark. There are a number of countries, particularly in Scandinavia, that have a national registry of diseases, treatments, and outcomes. We are relying here on data from Denmark, but I would have no reason to believe it's any different than what we might see in the United States. We're looking at registry data from 1986 to 2016. The analysis was performed in August 2022. Again, what they were looking at here is the risk of suicide attempts among spouses of individuals with cancer. Clearly, we were looking at registries that relate to cancer, and then they would also have other registries related to attempted suicide or actual suicide deaths, a nd they were matching these databases. It's obviously complex registry data, which of course, we would not have in the United States, but it's potentially very relevant. T he term they used was exposed individuals, these were the spouses of individuals with cancer. There were 409,000 individuals, and they compared that to over 2 million individuals who would be unexposed. These must be individuals in the population, presumably age matched, without cancer. They saw that the risk of a suicide attempt among spouses of patients with cancer was much higher than the population without cancer,particularly notable in the first year after diagnosis. The hazard ratio of those at risk versus not at risk for a suicide attempt was 1.45, and 2.56 for suicide death for the exposed compared to the unexposed, two-and-a-half-time risk. It's noted in the paper that there was even a higher risk — and I think the numbers will get smaller here — if that family member was diagnosed with an advanced-stage cancer or if the individual died of cancer. This is not surprising. Clearly there's much to be discussed here, but the most important point to be made is the stress — both psychological and financial, fear, risk of depression (particularly in an individual who might already have some concerns) — is very real, and this paper makes it very palpable. As emphasized in the paper, b ehavioral support, social work support, and financial support over time, particularly at the beginning of the cancer journey, is really important. What we can do as individuals, as family, as friends, but also as a healthcare establishment, either at an individual physician level or at a public health level, to help families and to help spouses through this journey is critical to potentially avoidsuicide and certainly suicide deaths. This is a very complex subject and a very personal subject for many individuals but a very important one. Thank you for your attention.
Business Wire
15-05-2025
- Health
- Business Wire
City of Hope Research Spotlight, February/March 2025
LOS ANGELES--(BUSINESS WIRE)--City of Hope® Research Spotlight offers a glimpse at groundbreaking scientific and clinical discoveries advancing lifesaving cures for patients with cancer, diabetes and other chronic, life-threatening diseases. Each spotlight features research-related news, such as recognitions, collaborations and the latest research defining the future of medical treatment. This roundup highlights diabetes research, the role of obesity in multiple myeloma, results from a clinical trial of a new liquid biopsy for evaluating potential responses to epidermal growth factor receptor (EGFR) inhibitors in metastatic colorectal cancers, the discovery of a biomarker that could predict a patient's response to immune checkpoint inhibitors, a scientific statement from the American Heart Association on addressing cardiovascular toxicity in patients who had pediatric cancers and a study of a new medication that helps stop leukemia cells from decreasing the activity of the immune system. To learn more about research at City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States, with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report, subscribe to City of Hope Research Spotlight. HIRN Closes the Gap Between Vision and Victory in Type 1 Diabetes A new report highlights the remarkable advances made in type 1 diabetes research since the National Institute of Diabetes and Digestive and Kidney Diseases established the Human Islet Research Network (HIRN) in 2014. Lead author John Kaddis, City of Hope associate professor in the Department of Diabetes and Cancer Discovery Science within the Arthur Riggs Diabetes & Metabolism Research Institute, and members of the HIRN reflect on the past, present and future of type 1 diabetes research. The HIRN was formed to bring together experts from around the world to solve intractable problems in type 1 diabetes. The article describes the milestones, achievements and critical goals of type 1 diabetes research, including: Pioneering advances, technologies and systems that uncover the interactive role of insulin-producing beta cells within their physiological environment. Innovative tools, disease models, devices and strategies that promote novel discoveries. Shared resources, data access and interdisciplinary training to challenge scientific dogmas. Although significant progress has been made, Kaddis emphasizes that successful approaches to preventing type 1 diabetes are still in their infancy. Kaddis and colleagues point out knowledge gaps in the processes underlying human beta cell loss, protection and replacement in type 1 diabetes. Contributions by the HIRN are expanding scientific knowledge about the causes of type 1 diabetes and expediting the development of effective strategies to prevent, diagnose and treat the disease, the authors concluded. For more information, see the journal article in Diabetes. Exploring the role of obesity in progression from precursor condition to multiple myeloma Patients with multiple myeloma incur some of the highest costs in cancer care to manage their disease. So, it's imperative that people with a precursor condition called monoclonal gammopathy of undetermined significance (MGUS) know the risk factors that make progression to myeloma more likely. To learn more about the role obesity plays in MGUS progression to cancer, a team led by Lawrence Liu, M.D., clinical fellow in hematology and medical oncology at City of Hope, and co-authors Murali Janakiram, M.D., M.S., of City of Hope and Su-Hsin Chang, Ph.D., of Washington University School of Medicine, which reviewed body mass index measurements over time in a cohort of nearly 22,500 people with MGUS. The team's findings, published recently in JAMA Network Open, suggest that maintaining a healthy weight may prevent MGUS from developing into myeloma. Using data collected about the patients by the U.S. Veterans Health Administration, the researchers tracked exposure to elevated body mass index for three years post-MGUS diagnosis. Of the study participants, 21.7% had a healthy BMI between 18.5 to less than 25 at baseline. For this population, an increase of elevated BMI over time was associated with a higher risk of progression. Participants whose baseline BMI was 25 or greater had a 17% to 27% higher risk of progression to myeloma compared with patients with baseline BMI within the reference range. The researchers believe this cohort study is the first to quantify the association between cumulative exposure to BMI 25 or greater and the progression from MGUS to myeloma. For more information, see the JAMA Network Open paper. Predicting outcomes of EGFR inhibitors in metastatic colorectal cancer In a recent paper published in Clinical Cancer Research, researchers from City of Hope, including corresponding author Ajay Goel, Ph.D., professor and chair of the Department of Molecular Diagnostics and Experimental Therapeutics, reported on outcomes from a clinical trial of a test to predict responses to certain medications in metastatic colorectal cancer (mCRC) patients. The EXOsome and cell-free miRNAs of anti-EGFR ResistAnce (EXONERATE) interventional study developed, tested and validated a liquid biopsy to see how well it predicted progression-free survival, overall survival and objective response rate for two, first-line EGFR inhibitors — panitumumab or cetuximab — in mCRC. Chemotherapy-naïve mCRC patients with certain genes (RAS wild-type) known to respond to EGRF inhibitors were recruited for two nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The EXONERATE assay was developed using a technology called genome-wide small RNA sequencing to identify candidate biomarkers to predict good versus poor responders to the medications. There can be different responses to treatment based on where the primary tumor is located in patients with mCRC — the disease is characterized as either right-sided or left-sided — so the researchers tested and validated the assay in both populations. They reported that the EXONERATE assay was successful at robustly predicting progression-free survival and overall survival outcomes in patients with mCRC, both right- and left-sided, before they received either panitumumab or cetuximab. For more information, see the Clinical Cancer Research paper. Searching for biomarkers to assess likely immune checkpoint inhibitor response Immune checkpoint inhibitors, which block certain proteins that suppress the immune system so that their body can better fight cancer, have changed the landscape of cancer therapy in recent years. But because many patients do not see long-lasting benefits, better biomarkers are needed to assess likely response rates in patients. Recently, a team of researchers led by Kelly Mahuron, M.D., an assistant clinical professor of surgical oncology at City of Hope, sought to pinpoint biomarkers for a positive response to a certain type of immune checkpoint inhibitors called PD-1 pathway inhibitors. Building on prior knowledge that CD8+ tumor infiltrating lymphocytes (TILs) have been associated with PD-1 inhibitor response, they aimed to identify the subpopulations that have the most prognostic value. In a paper published in Cancer Research, Dr. Mahuron and other authors outlined a series of experiments to search for predictive biomarkers in 129 tumor samples from melanoma patients. Through studies that included single-cell analysis, the team found that advanced melanoma patients with more than or equal 20% of CD8+ TILs that co-expressed PD-1 proteins and CTLA-4 protein receptors (which they call CP Hi TILs) had better objective response rates and survival following PD-1 monotherapy than those below this threshold. Based on these results, they believe the biomarker assay they developed can be used to predict an immune checkpoint inhibitor response. The team utilized single cell RNA sequencing to further characterize CP Hi TILs and they found that this cell population contains a diverse mix of subpopulations. Their findings have important implications for optimizing checkpoint-based immunotherapy across other cancers. For more information, see the Cancer Research paper. Addressing Heart Health in Pediatric Cancer Survivors While pediatric patients represent just roughly 5% of new cancer cases each year, this population has high survival rates, making them vulnerable to therapy-related cardiovascular disease later in life. To highlight recent advances in the growing field of cardio-oncology, a group of committee members from the American Heart Association, including vice-chair Saro Armenian, D.O., M.P.H., the Barron Hilton Chair in Pediatrics and the director of the Childhood, Adolescent and Young Adult Survivorship Program, recently issued a scientific statement in the journal Circulation that offers updates on emerging concepts related to established cardiotoxic therapies. The authors note that an increasing recognition that nearly all cancer treatments can pose risks for future cardiovascular disease has led to close investigations of anthracycline chemotherapy and chest-directed radiotherapy. As a result, dose reduction, use of cardioprotection for anthracyclines, and modern radiotherapy approaches have contributed to improved cardiovascular outcomes for survivors. The statement includes considerations for newer treatments, such as small-molecule inhibitors and immunotherapies, that have expanded options for some patients but also revealed new cardiotoxic challenges. In addition, Dr. Armenian and the committee members focused on issues related to transition of care after cancer treatment, including surveillance and prevention strategies, examined the role physical activity should play in rehabilitation after pediatric cancer care, and provided updates on how to manage cardiovascular complications. By incorporating new strategies in an equitable manner, the authors say adult cardiologists can help improve the transition from pediatric to adult care and greatly influence long-term health-related outcomes for childhood cancer survivors who are at risk for cardiovascular disease. To read the entire statement, see the review paper in Circulation. Keeping leukemia growth in check For patients with chronic myeloid leukemia (CML), a goal of treatment is to keep the disease from progressing to a blast crisis (BC) or acute phase, in which the cancer becomes more aggressive. The mechanisms of transformation to the BC phase are not fully understood, but recent research led by Bin Zhang, Ph.D., associate professor in the Department of Hematologic Malignancies Translational Science, and Guido Marcucci, M.D., professor and chair of the Department of Hematologic Malignancies Translational Science, has revealed a new pathway that enables leukemia cells to decrease the ability of the immune system to fight CML growth. A paper in Nature Communications unveils how an acquired deficit of a microRNA called miR-142 can cause the loss of T cells that play a crucial role in attacking cancer as CML progresses to the BC phase. In addition, the miR-142 mutation allows leukemic stem cells to evade the immune system and further promote disease growth. However, the researchers also found that an miR-142 deficit can be promptly mitigated using a synthetic miR-142 mimic designed and synthesized at City of Hope called M-miR-142. Used alone or in combination with certain monoclonal antibodies and/or tyrosine kinase inhibitors, M-miR-142 extended survival in mouse models with BC CML. According to the study, the experimental findings add important insights to the mechanisms of BC transformation and may offer conceptually new treatment strategies. A wide range of preclinical studies for M-miR-142 are underway, as the team hopes for a rapid translation of their findings from bench to bedside. For more information, see the Nature Communications paper. Awards and Honors Ravi Salgia, M.D., Ph.D., City of Hope's Arthur & Rosalie Kaplan Chair in Medical Oncology, has been named a Highly Ranked Scholar — Lifetime in lung cancer and cancer by ScholarGPS, a scholarly analytics platform. ScholarGPS ranks scholars based on its unique quantification of research productivity, noteworthy impact and quality of scholarly work. The following awards were presented to City of Hope scientists during the 2025 American Association for Cancer Research (AACR) Annual Meeting: Daniel D. Von Hoff, M.D., F.A.C.P., was recognized at the AACR Partners in Progress Reception for his immeasurable contributions to AACR, cancer research and patient care. Enrique Velazquez Villarreal, M.D., Ph.D., M.P.H., M.S., received the 2025 AACR Minority and Minority Serving Faculty Scholar in Cancer Research Award. Kimya Karimi was a recipient of the 2025 Women in Cancer Research Scholar Award. Francisco (Paco) Carranza, Ph.D., and Eric Medina were both recipients of the AACR Minority Scholar in Cancer Research Award. Isaac Bishara was awarded the AACR Doreen J. Putrah Cancer Research Foundation Scholar-in-Training Award. Grant Funding Ling Li, Ph.D., City of Hope associate professor, Department of Hematologic Malignancies Translational Science, has received a National Cancer Institute grant of $3.58 million over a five year period for a study titled 'Targeting AMP Synthesis to Overcome Resistance to BH3 Mimetics in Acute Myeloid Leukemia.' About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked top 5 in the nation for cancer care by U.S. News & World Report at its core, City of Hope's uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope's growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope's affiliated group of organizations includes Translational Genomics Research Institute and AccessHope TM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.
Los Angeles Times
13-05-2025
- Entertainment
- Los Angeles Times
Pacific Symphony returns to Irvine for another ‘spectacular' summer season
Pacific Symphony, the resident orchestra of the Great Park Live amphitheater in Irvine, will return to the outdoor venue for another spectacular summer season, kicking off the Summerfest 2025 series with its traditional 'July 4th Spectacular.' This marks the second year the symphony has made Great Park Live its summer home, after the temporary live music venue replaced the FivePoint Amphitheater. 'We are thrilled to return for another season at Great Park Live, where music and community come together under the stars,' said Pacific Symphony president, John Forsyte. Presented by City of Hope Orange County, with support from the City of Irvine, the five-concert series will feature the Symphony's renowned conductors, including Pacific Symphony music director Carl principal pops conductor Enrico Lopez Yañez and principal pops conductor laureate Richard Kaufman. 'We know music has a transformative power to uplift, to bring people together, and to heal. That's something we celebrate at City of Hope Orange County,' Annette Walker, president of City of Hope Orange County said in statement. 'We look forward to celebrating another magical summer series with Pacific Symphony.' The Pacific Symphony performs more than 100 concerts each year. Its Summerfest series has become a fixture for outdoor entertainment in Orange County since 1987, when the orchestra began summer performances at Irvine Meadows, which became Verizon Wireless Amphitheatre. Later, the symphony moved to the Pacific Amphitheater in Costa Mesa before coming to the FivePoint Amphitheater in Irvine until its closure. The 'July 4th Spectacular' has become a patriotic tradition for the symphony and this year's Independence Day celebration will contain pieces that honor America and the iconic all-American hits from Jimmy Buffet and the Beach Boys. Led by Pops conductor laureate Richard Kaufman, the program will end with a fireworks display. On Aug. 2, Pacific Symphony uses the force with 'Star Wars: The Force Awakens in Concert.' The Pacific Symphony will perform the movie score live alongside the full-length feature film, making for an immersive experience for any Star Wars fan. On Aug. 23, attendees are invited to put on their boogie shoes for 'Disco Fever-Let's Dance!' as Lopez-Yañez is joined by vocalists Maiya Sykes and Ty Taylor to perform selections from the disco catalogue like 'Stayin' Alive,' 'I Will Survive' and 'The Hustle.' The show promises to be a fun but also deeply personal performance, inspired by Lopez-Yañez's father's love of disco. Then on Aug. 23, leads 'Beethoven's Emperor & Pictures at an Exhibition' with Michelle Cann on piano. The season closes out on Sept. 6 with the 'Tchaikovsky Spectacular.' Conducted by Francesco Lecce-Chong, the memorable program features Tchaikovsky's most iconic works, such as 'Piano Concerto No. 1' and 'Francesca da Rimini,' and crescendos into the incendiary '1812 Overture' complete with fireworks to punctuate the performance. The Great Park Live entertainment venue first opened in June 2024, serving the community as a temporary live music space until a more permanent venue is built at the Great Park. Forsyte noted that last summer's successful series encouraged the symphony to continue its summer tradition of playing music under the stars. 'This season builds on the energy of last year's Summerfest while introducing new, inspiring elements that elevate the experience,' said Forsyte. More elevated experiences are coming to the Great Park, as the the City of Irvine and the Great Park Board recently announced plans to add an aerial transport system known as 'Whoosh' to the park at the 2025 'State of the Great Park.' The event opened with a Pacific Symphony performance, and Forsyte said the symphony is happy to continue to bring orchestral music to the Orange County community in multiple capacities. 'We are dedicated to always bringing wonder, joy and connection through orchestral music,' said Forsyte. 'We can't wait to share these unforgettable moments with our community.' Pacific Symphony's Summerfest series runs July 4 to Sept. 6. Subscriptions are available with packages ranging in price from $189 to $580 with parking included. For details and tickets visit
