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Category: 3. Business
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UK's easyJet exceeds annual profit expectations, raises target for holidays business – Reuters
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Australia is bringing in ‘world first’ minimum pay for food delivery drivers – here’s how it will work | Gig economy
Food delivery companies in Australia have teamed up with the Transport Workers’ Union to set new minimum standards for delivery drivers, including a minimum hourly wage and accident insurance for injuries sustained on the job.
In a deal described as a “world first”, the country’s two largest food delivery services, DoorDash and Uber Eats, have submitted a joint application with the Transport Workers’ Union to the Fair Work Commission.
The deal still requires approval from the industrial umpire, but here’s what we know so far.
What is changing for delivery drivers and their pay?
The application to the FWC comes after a wide range of workplace reforms was introduced by the Albanese government, which included empowering the industrial umpire to set minimum standards for gig workers.
DoorDash, Uber Eats and the TWU have agreed on new protections for delivery drivers after years of talks. The deal is likely to have involved concessions from either side of the negotiating table, including the union agreeing to call the workers “employee-like”.
Among the protections that would be legally enforceable under the new standards is a minimum “safety net” rate of pay of at least $31.30 an hour which would come into effect from 1 July 2026 and increase slightly from 1 January 2027.
The safety net would apply to all modes of transport used by delivery drivers, with the rate varying slightly depending on the type of vehicle used.
The protections also include new dispute resolution processes, new engagement and feedback mechanisms, representation rights and accident insurance for injured workers.
Eric Ireland, a driver in Melbourne who has worked for several platforms, believes the new standards will result in an increase in pay because it means he and his colleagues will get paid even if they have to wait for a restaurant to finish preparing the food.
“The peace of mind that you are actually getting paid while you’re on the job … can only be a good thing,” he says.
Ireland says while some working conditions have improved since he started delivering food six years ago, pay has not kept up with the cost of living.
“I sort of worked out on average I get about $22 an hour before I pay for petrol,” he says. “Sometimes you can earn a lot more than that if you do what they call a ‘quest’, which is doing 10 jobs in a weekend or something.”
However, as the workplace relations expert Prof Alex Veen points out, the safety net is different to a “minimum wage” in the way you may typically think of one.
The deal does not include penalty rates for things such as working late at night and, Veen says, the minimum hourly rate does not apply to time spent waiting between delivery jobs.
“What it materially means for gig workers is that when they’re working in periods of low demand they are unlikely to make that as their hourly pay,” Veen, a lecturer at the University of Sydney’s business school, says.
But he says there are many positives to the deal, including clarifying who is responsible for insuring both vehicles and the workers themselves.
How will the accident insurance work?
The application to the FWC states that workers are responsible for maintaining third-party insurances on the vehicles they use for deliveries, so if they get in an accident and damage another vehicle the delivery platform will not be liable for the cost.
On the other hand, Uber Eats and DoorDash will have to organise and pay for personal accident insurance that “provides a reasonable minimum level of cover” for their delivery workers. As Veen points out, that is “obviously open to interpretation”.
The TWU says 23 gig workers have been killed in Australia since 2017 and the figure could be higher because some are never reported as workplace deaths.
Will customers pay more for food delivery?
While Uber Eats and DoorDash are yet to confirm how they plan to fund an increase in operating costs, Veen says the platforms are most likely to pass them on to consumers.
“They may try to pass some of the costs on to restaurants and they could take a smaller [profit] margin themselves, although that’s not in their interests to do so,” he says.
Dr Michael Rawling, an associate professor who teaches workplace law at the University of Technology Sydney, says there may be a small increase in the price of a takeaway ordered through a third-party delivery app.
“In Australia we like to see workers treated fairly and if the consumer knows that then I think they’ll cop a small increase,” he says.
Is it really a world first?
Rawling agrees the deal is “world leading” and “very significant”.
He says while the deal hasn’t been ratified by the FWC, the “major players” who will be affected by the new standard have agreed on its content, which the industrial umpire will factor into its decision.
“[Typically] what the parties have actually consented to is a preferred direction for the FWC to go into for that particular matter,” he says.
What comes next?
The FWC needs to approve the deal before it can come into effect.
Prof Andrew Stewart, a workplace relations expert at the Queensland University of Technology, says it is “not a done deal”, especially as the FWC will have to consult with other stakeholders – including other delivery platforms.
“Potentially a huge fly in the ointment is that the FWC is going to have to come to a view as to whether the workers are eligible for a minimum standards order,” he says. “Because there’s a perfectly credible argument that the workers are already employees [and not employee-like].”
Stewart says if the FWC ruled that food delivery drivers were employees and not “employee-like” this would be a landmark ruling that would likely result in a challenge from the delivery platforms that could go all the way to the high court.
He is not ruling out this outcome, even though he says it is more likely the FWC will accept the application as it stands.
“I do not want to understate the significance of this deal,” he says. “It is a really important agreement that makes it much more likely we will get a minimum standards order much more quickly than we would if the TWU and the platforms were fighting over the details.”
What does this mean for the gig economy more broadly?
Overall, Stewart says the agreement on the application brings Australia a lot closer to having a safety net for at least one part of the gig economy.
It could also influence future FWC decisions relating to minimum standards. At the moment, the commission is considering similar gig workers in other sectors including package delivery. And the TWU has previously flagged it will submit an application to cover ride-share drivers.
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Asian shares advance after Wall Street gets a lift from hopes for a Fed rate cut
BANGKOK — Asian shares mostly gained on Tuesday after U.S. stocks rallied on hopes the Federal Reserve will cut interest rates soon.
U.S. futures edged lower and oil prices also declined.
Tokyo’s Nikkei 225 was nearly unchanged at 48,628.85, after reopening from a holiday.
A plunge in technology giant SoftBank’s shares weighed on the market. It fell 10.3% on concerns that returns from its heavy investments in OpenAI may be threatened by the next generation Gemini artificial intelligenc e model that Google launched last week.
In South Korea, the Kospi gained 0.3% to 3,859.12. Taiwan’s Taiex jumped 1.5%.
Chinese markets also advanced. In Hong Kong, the Hang Seng climbed 0.4% to 25,821.47, while the Shanghai Composite index jumped 0.9% to 3,872.45.
E-commerce giant Alibaba, which was due to report its earnings late Tuesday, gained 1.6%.
Australia’s S&P/ASX rebounded to edge 0.1% higher, closing at 8,537.00.
U.S. markets will be closed on Thursday for the Thanksgiving holiday. A day later, it’s on to the rush of Black Friday and Cyber Monday.
The U.S. stock market rallied on Monday, at the start of a week with shortened trading because of the Thanksgiving holiday.
The S&P 500 climbed 1.5% to 6,705.12 in one of its best days since the summer. The Dow Jones Industrial Average rose 0.4% to 46,448.27, and the Nasdaq composite jumped 2.7% to 22,872.01.
Stocks got a lift from rising hopes that the Fed will cut its main interest rate again at its next meeting in December, a move that could boost the economy and investment prices.
The market also benefited from strength for stocks caught up in the artificial-intelligence frenzy. Alphabet, which has been getting praise for its newest Gemini AI model, rallied 6.3% and was one of the strongest forces lifting the S&P 500. Nvidia rose 2.1%.
Monday’s gains followed sharp swings in recent weeks, not just day to day but also hour to hour, caused by uncertainty about what the Fed will do with interest rates and whether too much money is pouring into AI and creating a bubble. All the worries are creating the biggest test for investors since an April sell-off, when President Donald Trump shocked the world with his “Liberation Day” tariffs.
Despite all the recent fear, the S&P 500 remains within 2.7% of its record set last month.
Several tests for the market lie ahead this week. One of the biggest will arrive Tuesday when the U.S. government will deliver data on inflation at the wholesale level in September.
Economists expect it to show a 2.6% rise in prices from a year earlier, the same as in August. A higher-than-expected reading could deter the Fed from cutting its main interest rate in December for a third time this year, because lower rates can worsen inflation. Some Fed officials have already argued against a December cut in part because inflation has stubbornly remained above their 2% target.
Traders are nevertheless betting on a nearly 85% probability that the Fed will cut rates next month, up from 71% on Friday and from less than a coin flip’s chance seen a week ago, according to data from CME Group.
In other dealings early Tuesday, U.S. benchmark crude oil lost 25 cents to $58.59 per barrel. Brent crude, the international standard, shed 30 cents to $62.42 per barrel.
The dollar fell to 156.70 Japanese yen from 156.91 yen. The euro slipped to $1.1517 from $1.1521.
Bitcoin fell 1.1% to $88,100. It was near $125,000 last month.
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Progress on share buyback programme
Amsterdam,
ING announced today that, as part of our €1.1 billion share buyback programme announced on 30 October 2025, in total 2,767,892 shares were repurchased during the week of 17 November up to and including 21 November 2025.
The shares were repurchased at an average price of €21.60 for a total amount of €59,777,931.11.
In line with the purpose of the programme to reduce the share capital of ING, the total number of shares repurchased under this programme to date is 7,899,202 at an average price of €22.02 for a total consideration of €173,950,206.98. To date approximately 15.81% of the maximum total value of the share buyback programme has been completed.
For detailed information on the daily repurchased shares, individual share purchase transactions and weekly reports, see share buy back programme.
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ING PROFILE
ING is a global financial institution with a strong European base, offering banking services through its operating company ING Bank. The purpose of ING Bank is: empowering people to stay a step ahead in life and in business. ING Bank’s more than 60,000 employees offer retail and wholesale banking services to customers in over 100 countries.
ING Group shares are listed on the exchanges of Amsterdam (INGA NA, INGA.AS), Brussels and on the New York Stock Exchange (ADRs: ING US, ING.N).
ING aims to put sustainability at the heart of what we do. Our policies and actions are assessed by independent research and ratings providers, which give updates on them annually. ING’s ESG rating by MSCI was reconfirmed by MSCI as ‘AA’ in August 2024 for the fifth year. As of December 2023, in Sustainalytics’ view, ING’s management of ESG material risk is ‘Strong’. Our current ESG Risk Rating, is 17.2 (Low Risk). ING Group shares are also included in major sustainability and ESG index products of leading providers. Here are some examples: Euronext, STOXX, Morningstar and FTSE Russell. Society is transitioning to a low-carbon economy. So are our clients, and so is ING. We finance a lot of sustainable activities, but we still finance more that’s not. Follow our progress on ing.com/climate.
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Factors associated with the avoidance of glaucoma surgery in secondary glaucoma due to ocular inflammatory disease | Journal of Ophthalmic Inflammation and Infection
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Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brézin AP (2016) Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. ;388(10050):1183-92. https://doi.org/10.1016/S0140-6736(16)31339-3. Epub 2016 Aug 16. Erratum in: Lancet. 2016;388(10050):1160. doi: 10.1016/S0140-6736(16)31538-0
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South African rand steady ahead of key indicator data – Reuters
- South African rand steady ahead of key indicator data Reuters
- South African Markets – Factors to watch on November 25 TradingView
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Novartis data underscore pioneering scientific innovation in Hematology and Oncology at ASH and SABCS
- Positive results from ianalumab pivotal Phase III trial in ITP patients previously treated with corticosteroids to be presented as late-breaker
- Scemblix data across clinical and real-world settings offer new evidence informing CML care amid evolving patient needs
- 96-week pelabresib Phase III data represent longest follow-up of first-line myelofibrosis patients in randomized combination trial
- Kisqali NATALEE and MONALEESA data add to evidence of long-term benefits for early and metastatic breast cancer patients
Basel, November 25, 2025 – Novartis will present data from over 70 abstracts, including investigator-initiated trials at the 67th American Society of Hematology (ASH) Annual Meeting & Exposition and 2025 San Antonio Breast Cancer Symposium® (SABCS). Featured among these latest advances in hematology and oncology are 11 oral presentations, with the Phase III VAYHIT2 trial for ianalumab in immune thrombocytopenia (ITP) accepted as a late-breaker abstract.
“For decades, Novartis has redefined the future of hematology and oncology, and we’re building on that foundation with compelling new data presented at ASH and SABCS,” said Mark Rutstein, M.D., Global Head, Oncology Development, Novartis. “These data underscore how we seek to set new standards for transformative care, with the aim of turning cutting-edge innovation into meaningful impact for patients.”
Key highlights of data accepted by ASH include:
Abstract Title Abstract Number/ Presentation Details Ianalumab (VAY736) Primary results from VAYHIT2, a randomized, double-blind, Phase 3 trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) who failed first-line corticosteroid treatment Abstract #LBA-2
Oral Presentation
December 9, 7:45 – 8:00 am ETSecondary analysis results from VAYHIT3, a Phase 2 study of ianalumab in patients with primary immune thrombocytopenia previously treated with at least two lines of therapy Abstract #844
Oral Presentation
December 8, 3:30 – 3:45 pm ETScemblix® (asciminib) Asciminib (ASC) demonstrates continued improvement in patient-reported outcomes (PROs) vs investigator-selected tyrosine kinase inhibitors (IS-TKIs) in newly diagnosed chronic myeloid leukemia (CML): ASC4FIRST week 96 analysis Abstract #1997
Poster Presentation
December 6, 5:30 – 7:30 pm ETImproved long-term tolerability with asciminib (ASC) vs investigator-selected (IS) tyrosine kinase inhibitors (TKIs) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): Week 96 exploratory analysis of the phase 3 ASC4FIRST trial Abstract #5549
Poster Presentation
December 8, 6:00 – 8:00 pm ETAsciminib (ASC) in chronic myeloid leukemia in chronic Phase (CML-CP): Efficacy and safety results of the Phase 2 ASC2ESCALATE trial in the cohort of patients (pts) with 1 prior tyrosine kinase inhibitor (TKI) Abstract #906
Oral Presentation
December 8, 4:00 – 4:15 pm ETA comparison of real-world outcomes of asciminib versus ATP-competitive tyrosine kinase inhibitors as second-line treatment in patients with chronic myeloid leukemia in chronic phase Abstract #724
Oral Presentation
December 7, 5:15 – 5:30 pm ETPelabresib (DAK539) Durable efficacy and long-term safety with pelabresib plus ruxolitinib in JAK Inhibitor–Naive myelofibrosis: 96-week Results from the Phase III MANIFEST-2 study Abstract #910
Oral Presentation
December 8, 3:30 – 3:45pm ETRapcabtagene autoleucel (YTB323) Rapcabtagene autoleucel (YTB323) for patients with first line high-risk large B-cell lymphoma: phase II interim results Abstract #670
Oral Presentation
December 7, 5:15 – 5:30 pm ETFabhalta® (iptacopan) Oral iptacopan monotherapy demonstrates clinically meaningful hemoglobin increases in patients with paroxysmal nocturnal hemoglobinuria with baseline hemoglobin levels 10 to <12 g/dL on anti-C5 therapy: Subgroup analysis of the APPULSE-PNH Phase 3b trial Abstract #4981
Poster Presentation
December 8, 6:00 – 8:00 pm ETLong-term safety and efficacy of iptacopan in patients with paroxysmal nocturnal hemoglobinuria: 4- and 5-year follow-up of patients from phase 2 studies who entered the roll-over extension program Abstract #3198
Poster Presentation
December 7, 6:00 – 8:00 pm ETThe 2-year efficacy and safety of iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria with a history of aplastic anemia on concomitant immunosuppressive therapy who entered the roll-over extension program Abstract #4978
Poster Presentation
December 8, 6:00 – 8:00 pm ETKey highlights of data accepted by SABCS include:
Kisqali® (ribociclib) Pooled analysis of patients (pts) treated with 1st-line (1L) ribociclib (RIB) + endocrine therapy (ET) in the MONALEESA (ML) studies: long-term progression-free survival (PFS) Abstract # PD5-10
Poster Spotlight Presentation
December 11, 8:09 – 8:12 am CSTFive-year analysis of distant disease-free survival (DDFS) across key subgroups from the phase 3 NATALEE trial of ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) in patients with HR+/HER2− early breast cancer (EBC) Abstract # PS3-09-08
Poster Presentation
December 11, 12:30 – 2:00 pm CSTProgression-free survival (PFS) and overall survival (OS) results from the phase 3 MONALEESA-3 trial of postmenopausal patients with hormone receptor–positive (HR+)/HER2-negative (HER2−) advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL): A subgroup analysis of patients with invasive lobular carcinoma (ILC) Abstract # PS1-10-27
Poster Presentation
December 10, 12:30 – 2:00 pm CSTRibociclib drug-drug interaction and concomitant medication management in early and advanced breast cancer patients Abstract # PS3-09-15
Poster Presentation
December 11, 12:30 – 2:00 pm CSTReal-world patient (pt) and caregiver experiences with breast cancer (BC) risk of recurrence (ROR) in the US: Results of an Online Survey and Social Media Analysis Abstract # PS1-04-17
Poster Presentation
December 10, 12:30 – 2:00 pm CSTRepower: a real-world noninterventional study of outcomes and experiences in patients with hormone receptor-positive (HR+)/human epidermal growth fact receptor 2-negative (HER2−) early breast cancer (EBC) treated with an adjuvant cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) plus endocrine therapy (ET) Abstract # PS3-08-27
Poster Presentation
December 11, 12:30 – 2:00 pm CSTProduct Information
For full prescribing information, including approved indications and important safety information about marketed products, please visit https://www.novartis.com/about/products.
Novartis in hematology
Our legacy in hematology runs deep, shaped by over 25 years of progress, partnerships and a commitment to keep asking questions, challenging norms and striving for better answers in a uniquely complex field. In the past two decades, we have delivered more than 10 medicines across more than 15 blood cancers and serious blood disorders including leading the era of targeted therapies in cancer and bringing the first CAR-T therapy to patients.Innovation in hematology has brought significant progress, yet patients and clinicians continue to face persistent challenges. We’re forging the future of hematology, powered by our foundation in scientific discovery to deliver meaningful change for patients with unmet needs.
Novartis in breast cancer
For over 30 years, Novartis has been at the forefront of driving scientific advancements for individuals affected by breast cancer and enhancing clinical practice in collaboration with the global community. With one of the most comprehensive breast cancer portfolios and pipeline, Novartis leads the industry in discovery of new therapies and combinations in HR+/HER2- breast cancer, the most common form of the disease.Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide.Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.
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MIF/CD74 axis regulates alveolar epithelial type II cell apoptosis, autophagy, and transdifferentiation in bronchopulmonary dysplasia via the TGFβ1/SMAD4 pathway | Respiratory Research
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CAR T-Cell Therapy for HER2+ Breast Cancer With CNS Metastases
A phase 1 clinical trial presented at the 2025 Society of Neuro-Oncology Annual Meeting reported encouraging early safety findings for intraventricular HER2-directed CAR T-cell therapy in patients with HER2-positive breast cancer who developed recurrent brain metastases or leptomeningeal metastases (LM)—two of the most devastating complications in advanced HER2-driven disease.
Led by Jana Portnow, MD, from City of Hope, this first-in-human study demonstrated that intraventricular administration of HER2-targeted CAR T cells, with or without lymphodepletion, was feasible, safe, and capable of inducing disease stabilization in a heavily pretreated population with few therapeutic options.
Background: A Critical Unmet Need in HER2+ CNS Progression
HER2-positive breast cancer is known for its propensity to metastasize to the central nervous system (CNS). Patients with recurrent brain or leptomeningeal disease after radiation or intrathecal chemotherapy typically have poor prognosis and limited access to effective therapies. Traditional CAR T-cell therapy has been largely restricted to hematologic cancers. Delivering CAR T cells directly into the CSF through the ventricular system offers a way to bypass the blood–brain barrier and target tumor cells within the CNS.
This phase 1 trial represents one of the first efforts to test HER2-directed CAR T-cell therapy specifically for breast cancer CNS metastases.
Study Design
This single-center, phase 1 trial (NCT03696030) enrolled adults with:
- HER2-positive breast cancer (IHC 3+ or FISH amplified)
- Recurrent brain metastases after radiation or
- Recurrent leptomeningeal metastases after intrathecal therapy
- Karnofsky Performance Status ≥70
- No limit on prior lines of therapy (patients received a median of 4–6 prior chemotherapies)
Patients were required to pause systemic chemotherapy or endocrine therapy during the first 3 CAR T cycles, and dexamethasone >6 mg/day was prohibited to avoid suppression of CAR T activity.
Treatment Approach
In this phase 1 study, patients were assigned to one of two treatment strategies. The first cohort received HER2-directed CAR T-cell therapy alone, while the second cohort received lymphodepletion followed by CAR T-cell therapy. Lymphodepletion consisted of a short course of cyclophosphamide (300 mg/m²/day) and fludarabine (25 mg/m²/day)administered for three consecutive days, a regimen intended to enhance CAR T-cell expansion by reducing immune competition.
Following lymphodepletion (or directly, in the non-LD cohort), CAR T cells were administered intraventricularlythrough an Ommaya reservoir. The treatment used an escalating dose design to evaluate safety across increasing levels of cellular therapy. Patients received CAR T infusions starting at Dose Level 1 (2 × 10⁶ cells in the first cycle, then 10 × 10⁶ cells in subsequent cycles), progressing to Dose Level 2 (10 × 10⁶ → 50 × 10⁶ → 50 × 10⁶), and Dose Level 3, the highest explored level (20 × 10⁶ → 100 × 10⁶ → 100 × 10⁶).
The primary objective of the study was to determine the safety and tolerability of delivering HER2-directed CAR T cells directly into the CSF. Secondary assessments evaluated how long CAR T cells persisted in both cerebrospinal fluid and peripheral blood, along with associated cytokine fluctuations that reflect immune activation. Investigators also monitored central nervous system clinical benefit, including the durability of stable disease, as well as median CNS progression-free and overall survival.
Safety Findings
Overall, intraventricular HER2-directed CAR T-cell therapy demonstrated a manageable safety profile across both treatment cohorts. The most frequently observed adverse events were low-grade (grade 1/2) symptoms, including headaches, nausea, vomiting, fever, fatigue, and myalgias. These effects typically appeared within the first 24 to 48 hours after each infusion and resolved quickly with supportive care.
Neurotoxicity: Two patients who received lymphodepletion experienced mild immune effector cell–associated neurotoxicity syndrome (ICANS), presenting as transient confusion and lethargy. No higher-grade neurotoxicity was observed.
Dose-Limiting Toxicities: In the cohort that received lymphodepletion followed by CAR T-cell therapy, investigators reported two dose-limiting toxicities—both grade 3 headaches. These events prevented patients from receiving all planned CAR T-cell doses and highlighted a clearer toxicity signal when lymphodepletion was added.
Impact of Lymphodepletion: The addition of lymphodepletion increased the overall rate and severity of toxicities but did not improve the durability of stable disease. However, lymphodepletion did appear to enhance biologic activity of the CAR T cells, as reflected by greater evidence of on-target immune activation and increased CAR T-cell persistence in the cerebrospinal fluid.
Efficacy: Disease Stabilization Achieved
Although responses were modest, stable disease (SD) was achieved in both treatment groups.
Cohort 1: CAR T Alone (n = 10)
- SD rate: 44%
- Median duration of SD: 56 days (range 50–136 days)
Cohort 2: LD + CAR T (n = 13)
- SD rate: 64%
- Median duration of SD: 56 days (range 44–134 days)
No partial or complete responses were observed, which is expected in a phase 1 CNS CAR T safety trial. Importantly, patients with SD often exhibited clinical stabilization despite being heavily pretreated.
Correlative Analyses: Evidence of Biological Activity
Correlative studies offered important insights into how the intraventricular HER2-directed CAR T cells behaved in the central nervous system and how the immune system responded to therapy.
CAR T-Cell Persistence in the CSF
Analyses showed that CAR T-cell persistence in the cerebrospinal fluid increased with escalating dose levels. Persistence was even more pronounced in patients who also received lymphodepletion, suggesting that reducing baseline immune cells may create a more favorable environment for CAR T expansion and survival.
In several patients, repeated CAR T-cell dosing led to the gradual disappearance of malignant cells on CSF cytology—an encouraging sign of biological activity.Cytokine Dynamics
HER2-directed CAR T-cell infusion triggered a measurable rise in pro-inflammatory cytokines in the CSF, such as IL-2 and IFN-γ, reflecting active CAR T-cell engagement with tumor targets. Over time, these cytokines declined, while anti-inflammatory cytokines became more prominent, indicating a shift in the immune landscape as the CNS adapted to treatment.
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Using MediaPipe to track upper-limb reaching movements after stroke: a proof-of-principle study | Journal of NeuroEngineering and Rehabilitation
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