Category: 3. Business

A couple of years ago, 31-year-old charity worker Nicki Wedgwood had ordered Christmas presents online for friends and family. When the packages were delivered to her in Hackney, east London, the driver left them in the lobby of her building rather than taking them directly to her flat. She spotted them as she popped out to a nearby shop and decided to pick them up when she came back. When she returned 10 minutes later, the boxes had been ripped open and their contents were gone.

Wedgwood thinks she passed the thief in the hallway as she was leaving for the shop. “There was some random dude just inside the doorway, who had a Boris bike with him,” she says. She had assumed he was a guest of one of her neighbours. “I said hello to him … I think he even said Merry Christmas.”

Wedgwood and her flatmates have had “so much stuff stolen over the years”, she says. The external door to their block of flats is glass, so thieves can peer in and see packages that have been dropped off in the lobby. She believes there are thieves in her local area who follow delivery drivers on bikes “and immediately push on the door after the driver has driven off. If that’s been left open, they can just get the parcel – and a lot quicker than the person it’s for, who is maybe 15 floors up.”

Parcel theft has become a growing issue, with parcels worth a record-breaking £666.5m reported as stolen across the UK in the last year, according to data obtained by the technology company Quadient, nearly £290m more than in 2024. And those figures are just reported thefts, while many more go unreported. Wedgwood was able to get a refund from the retailer, and says she didn’t see any point in telling the police about the incident, given that when she has reported other crimes to them: “They just take a picture and you never hear anything again.” (A spokesperson for the Metropolitan police advises victims to “always report thefts to the police”, and said it is “carrying out intelligence-led operations to catch the criminal gangs who prey on delivery vans, which has already resulted in a number of arrests”.)

Why has this crime become so common? We know that people are buying more online than ever before but, according to Gary Winter, the vice-president of global strategic initiatives at Quadient, the increase in parcel thefts isn’t just proportional to the rise of online shopping – it’s bigger than that. Winter doesn’t believe that the rise is because people are getting better at reporting it. “I genuinely think it’s becoming more frequent,” he says. “People see it as a low-level crime opportunity and are taking advantage of it.”

Leicestershire is the UK’s hotspot for parcel thefts, according to Quadient’s data (which doesn’t include figures from every British police force, as not all of them responded to the company’s freedom of information request), but city and town centres in general are where the greatest risk is. “It’s more likely that you haven’t got a safe place, that you’re living in an apartment or a multi-occupied building,” says Winter. In peak delivery season – unsurprisingly, parcel thefts are highest in December – piles of parcels can build up in lobbies and on doorsteps, and in busy areas where people don’t necessarily know their neighbours, and thieves can help themselves without too much difficulty.

Darren Walmsley, the vice chair of the National Courier and Despatch Association, thinks part of the reason parcel thefts are becoming so common is a change in the way deliveries are made. In the past, far more deliveries had to be signed for. With a signed-for delivery, he says: “Generally, you’re physically handing it over to someone, and therefore it’s a secure delivery.” In his personal view, it was when Amazon came on the scene that things started to change. It popularised delivering items without requiring proof of delivery, having worked out that it was more cost-efficient to risk having to refund losses than for drivers to take the extra time to get a signature. Then, during the Covid pandemic, contactless delivery became more common.

Independent courier companies that offer a same-day service are “the only guaranteed service there is”, says Walmsley. Multi-job couriers tend to have much less time for each delivery: “They’ll be asked to do 100-plus deliveries a day, whereas a same-day delivery driver might do 10 deliveries a day, so they can afford to take a lot more time. For example, if someone elderly ordered something quite large, the courier would be more able to assist them to get the package inside.”

Overstretched delivery drivers leaving parcels outside, or not closing doors properly as they leave a building, “is a large part of the problem”, says Wedgwood, though she admits she wouldn’t want to do their job. The trouble is that retailers and customers tend to look for the cheapest delivery options, which usually means a lower-quality service. Walmsley advocates opting for same-day delivery when you can. “The perception is that same-day is always significantly more expensive than overnight deliveries,” he says. “However, that’s not always strictly true. The bigger an item or the higher its value, and the closer the collection and delivery locations are to each other, the more cost-effective same-day deliveries become.”

Though the value of Wedgwood’s parcels came to about £100 in total – they contained trinket gifts and books for her family – the most expensive item was only worth £30. “I definitely don’t feel like you’d get a good price for them [in the secondhand market],” she says. What can be sold on more easily, however, is branded sportswear – and Winter’s research has shown that more of these items go missing, suggesting that thieves target parcels with sports brand packaging. “We know that they end up at places like car boot sales,” he says. “They end up on eBay or Facebook Marketplace or various other platforms to be resold.”

It is not only organised criminals who are taking advantage of parcels being left outside – opportunistic neighbours are another culprit. Asif, who lives in Derbyshire, had a parcel stolen from behind his bin, where it had been left by the courier, and he suspects his neighbour was responsible. “He denied it,” says the 53-year-old. But “I could tell from his face”.

Maddie from Bristol has a little more evidence to suggest that her neighbours were the culprits when her weekly box from the meal kit service Gousto went missing. She went downstairs to her building’s basement flat to ask its student occupiers if they had seen it. “They were in the process of moving out, and the cleaner, who was conducting the end-of-tenancy clean, answered,” she says. The cleaner claimed not to have seen the box, but as Maddie turned to leave, she saw “a pile of black sacks by the door in the alleyway, and poking out of one was the patterned cold box you get as part of a Gousto. We are 99% sure it was our box as no one else in the past has had a Gousto delivery to our building.” Though it was obviously disappointing to miss out on that week’s meals, Maddie was able to get a full refund from Gousto.

Even with police involvement, it can be difficult to catch parcel thieves, although it is sometimes possible with the help of video doorbell footage – as in the case of Peter Storer, who was caught on camera stealing from a woman’s doorstep in Leicester. Even if victims don’t have any evidence, Winter says it is important to report it. “You’ve got to report it to the police because you want to be in the statistics. You want to try to make sure that the police are paying attention to this.”

Some people, of course, have taken justice into their own hands. It is testament to how widespread the frustration about this issue is that videos of doorstep thieves, or “porch pirates” as they have become known, being tricked have gone viral on social media. Pranksters have left out “bait packages” that, when picked up, will set off everything from paint bombs to glitter explosions, with front-door cameras ready to capture the thief’s comeuppance. Arizona-based software engineer Alec Armbruster, who has had a number of parcels stolen, says he enjoys watching such videos because laughing at the thieves’ plans backfiring is “the only way I can take back control”.

Several years ago, Armbruster made a prank video of his own, filling a bait package with used cat litter. “I think it took a week and a half for the box to get picked up,” he says. “I came home one day and it was gone and I was like, ‘Yes!’ I ran inside to watch the footage. It was very exciting.” He had become used to having his parcels stolen, and says he would report every one. “Typically, they would send out an officer and I would never hear about it again.” So he decided to take matters into his own hands via the prank, “which helped because it turned from something extremely frustrating to something exciting and entertaining”.

He thinks the video was popular on social media because “it’s just extremely satisfying. We’ve all had things stolen from us and it’s very invading. And we all want to see justice for things like this. If someone thinks they are stealing something expensive, like an iPhone, but what they actually get is just dust, it’s quite funny.” That said, Armbruster admits that his prank “didn’t really bring justice”, in terms of stopping parcels getting stolen. “I thought or hoped it would, which sucks.”

There are more effective steps that can be taken to prevent parcel thefts. “The brands could do more to anonymise parcels or make it less attractive or less obvious to thieves that there might be something interesting inside,” Winter says. “Carriers can re-emphasise to their delivery agents: ‘Do not put things in a stupid place, if it’s visible from the road or visible to everybody.’” Instead, they should tell them to try “knocking the door a bit harder and waiting a few seconds”, though he says he is loth to criticise the carriers because, “they’re under massive pressure to deliver such high volumes, particularly at this time of year”.

Consumers need to play their part in preventing these thefts, too, by making sure they are ordering a delivery for a day they will be in, and providing the correct address. “It’s amazing how many times we see addresses given incorrectly,” Walmsley says. He also recommends buyers consider the different delivery methods on offer. “See if they’ve got signed-for options or carriers that you’ve used before, who you know you’ve received good delivery service from.” It could also be worth getting packages delivered to your work address, he says. “Business deliveries are a lot more successful.”

Winter agrees. “If you live in an apartment with no front garden or you’re on a street with a lot of visibility then, when you order, don’t have it delivered to home, select an out-of-home option.” He recommends corner shop and locker deliveries. He admits he has a vested interest in lockers because Quadient provides smart parcel locker solutions, but says he genuinely believes that “it’s a very convenient way to reduce that risk”.

Since Wedgwood’s parcels were stolen, she has become “quite paranoid” when she makes online orders. If she is out and receives a message to say something has been delivered, she texts her housemates to ask them to fetch it straight away. “When the buzzer goes now, we try to ask: ‘What’s the name on the parcel?’” before letting the courier in, to weed out impostors. She is not taking any chances, especially since she believes her parcel thief came back last year. “My flatmate said: ‘So weird, I’ve just come in and downstairs there was a random Boris bike left in the hallway.’ Alarm bells immediately went off,” she says.

Since Wedgwood has not had any luck asking her landlord to make her building more secure, she doesn’t expect the thieves to back down anytime soon. Unlike Armbruster, who managed to stop his parcels being stolen by moving to a more rural area, Wedgwood is not willing to find a new home because of this. “The rent is really low. I love the area. Also, I just don’t want to let the thieves win,” she says. “Why should I let them?”

Thompson, chairman of the Chief Executive Alliance and previously ranked as the world’s top CEO coach, and Loflin, Nasdaq’s Global Head of Board Advisory, joined forces to provide a 360-view of this loaded moment for leadership, from the C-suite and board perspectives, respectively. In a wide-ranging conversation with Fortune, they talked about the Shakespearean themes of leadership and turmoil and the feeling that “heavy is the head that wears the crown.”

For those aspiring to reach the top, Thompson shared the conventional wisdom he’d learned from his mentor, Marshall Goldsmith: “What got you here got you halfway there.” (Goldsmith had a New York Times bestseller in 2007 with What Got You Here Won’t Get You There.)

The transition from being a high-performing executive in a “swim lane” to having the “aperture of having a full enterprise” requires substantial new learning and skill development, Thompson argued, because no matter how great an executive you are or how prepared you think you might be, the stakes are existentially high. The risk that a CEO might “lose his or her head within the next year or so” is “easily like 20% or at the big brands It feels like it’s twice that,” said Thompson, who recently penned an essay on the subject of CEO “decapitation” for Fortune.

Adding to this pressure, Thompson and Loflin added, is the radical shift in board member expectations. Board members, who once might have been “golf buddies,” are now “really under the gun to perform.” They are “less patient” and expected to “actually deliver,” based on their subject matter expertise.

This environment demands nearly every candidate be ready to serve as a “peacetime in a wartime CEO,” Thompson said, capable of harvesting the best aspects of the company culture while also being “disrupting and breaking new ground.” An executive promoted from a functional role, such as a CFO, may possess the “gravitas of understanding the street and the shareholders,” but often lacks the breadth to “light hearts and minds” across the workforce, or do “ride-alongs with customers.”

The loneliness of the tower, and ‘relationology’

Fortune has been tracking this tenuous moment for leaders throughout 2025. Top recruitment firm Challenger, Gray & Christmas found 1,235 CEOs had left (or lost) their jobs through the first half of 2025, a stunning 12% increase from 2024 and the highest year-to-date total since Challenger began tracking CEO turnover in 2002.

Jim Rossman, Barclays’ global head of shareholder advisory, who’s been closely tracking shareholder activism for decades, similarly found record activist-linked turnover at the top for 2025. “It feels like what activists have done is basically [to hold] public companies to the standards of private equity,” Rossman told Fortune in a previous interview, as they have come to view the CEO “more as an operator, not somebody who’s risen through the ranks.” In other words: Results matter.

The intense environment contributes to feelings of isolation. As CEOs often note, being the boss is a lonely job where leaders are caught in the middle, with information they cannot share with reports but must share with the board, creating a huge information asymmetry, as Microsoft CEO Satya Nadella previously told McKinsey.

Carolyn Dewar, the co-leader and founder of McKinsey’s CEO Practice, previously told Fortune that “No one else in your organization or above you, like your board or your investors, see all the pieces you see.” She advocated for leaders to surround themselves with trusted advisors—“a kitchen cabinet” of sorts.

Similarly, Loflin told Fortune he’s fond of the concept of “relationology,” which he describes as “sort of a study of relationships.” He suggested leaders must develop a “portfolio of relationships of intimacy” that are “very context-relevant.” A leader’s effectiveness hinges on having fluency, for instance, when speaking to a CFO about analyst days, or working with a compliance team to keep the business safe or connecting authentically with union executives. Loflin said he’s often seen it being a “big surprise” to accomplished leaders that they have, say, seven different groups they need to engage and maybe as many as six new skills to really flesh out before they’re ready to take the enterprise to the next level.

This need for deep, context-aware connection also applies to personal life, Loflin added. The idea that a personal life and professional life can be entirely separate “undermines leadership and undermines the fabric of a company.” Critically, Loflin said, the chair must really know his CEO “at a deep level, like a Shakespearean level,” requiring a transparency that ensures appropriate accountability. After all, Loflin noted as one example, boards have to be mindful that a personal relationship that violates company policy can jeopardize corporate governance at the drop of a hat. The board really needs to know who their CEO is, maybe better than the CEO knows themselves.

The power and the privilege, the hubris and the humility

Loflin, who admitted to Fortune that he’s a bit of a Shakespeare nerd, noted the difference between a tragedy and a comedy is determined by “the vulnerability and the self-awareness of the protagonist,” and a tragic outcome results from a feeling he likened to “never recognizing whether I needed to grow or change.”

Thompson added that surviving as a CEO requires an “odd combination” of traits you might read in a Greek tragedy: hubris and humility.

The CEO must possess the hubris, or excessive pride, to believe they can be the best in their field, but also the profound humility that acknowledges they can’t do it alone.

The professional mandate is relentless, Thompson added, citing a key interview for the book from Qualcomm CEO Cristiano Amon: if you were the “same guy you were a year ago, you don’t deserve to be promoted.” Thompson said he thinks of hubris of being at “the edge of your competence, so rather than retreating, you actually should lean into that” to acquire the skills and help you need to keep growing as a professional.

For top leaders, Thompson said, the top job is not a prize to be won, but a “privilege to do this role.” Just as Olympic athletes must constantly improve, he added, leaders must recognize that breaking a record only attracts more competition.

Loflin urged boards and executives alike to move beyond a Wolf of Wall Street mindset and into “what it means to authentically care for and build the confidence and foster appropriate accountability.” He said that for many executives, admitting you have areas to improve on and get better at is a “special vulnerability.” He argued boards need more genuine, interpersonal affection—sometimes of the tough love variety—is needed to prevent a truly Shakespearean tragedy on their watch.

Loflin said he’d just had breakfast with a board director for a $30 billion company and the subject of love arose: “Do you love your management team?” The director said yes, definitely, almost like relatives. After all, they had been with the company over a decade and come to have deep relationships with other directors and their C-suite. Loflin argued that over decades of advising boards on corporate governance, he wishes more would adopt this sort of attitude.

“I don’t think it’s going to hurt anything in business because a good father has to talk to a troubled son, hopefully he’s mentoring when [the son is] getting himself in trouble.” After all, Loflin continued, “bad stuff happens, and I think some of these metaphors are important.” In other words, it shouldn’t be the Wolf of Wall Street, but the wolf—or the activist—is always at the door.

(Bloomberg) — Wall Street’s sentiment toward companies associated with artificial intelligence is shifting, and it’s all about two companies: OpenAI (OPAI.PVT) is down, and Alphabet Inc. (GOOG, GOOGL) is up.

The maker of ChatGPT is no longer seen as being on the cutting edge of AI technology and is facing questions about its lack of profitability and the need to grow rapidly to pay for its massive spending commitments. Meanwhile, Google’s parent is emerging as a deep-pocketed competitor with tentacles in every part of the AI trade.

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“OpenAI was the golden child earlier this year, and Alphabet was looked at in a very different light,” said Brett Ewing, chief market strategist at First Franklin Financial Services. “Now sentiment is much more tempered toward OpenAI.”

As a result, the shares of companies in OpenAI’s orbit — principally Oracle Corp. (ORCL), CoreWeave Inc. (CRWV), and Advanced Micro Devices Inc. (AMD), but also Microsoft Corp. (MSFT), Nvidia Corp. (NVDA) and SoftBank, which has an 11% stake in the company — are coming under heavy selling pressure. Meanwhile, Alphabet’s momentum is boosting not only its stock price, but also those it’s associated with like Broadcom Inc., Lumentum Holdings Inc., Celestica Inc., and TTM Technologies Inc.

The shift has been dramatic in magnitude and speed. Just a few weeks ago, OpenAI was sparking huge rallies in any company related to it. Now, those connections look more like an anchor. It’s a change that carries wide-ranging implications, given how central the closely held company has been to the AI mania that has driven the stock market’s three-year rally.

“A light has been shined on the complexity of the financing, the circular deals, the debt issues,” Ewing said. “I’m sure this exists around the Alphabet ecosystem to a certain degree, but it was exposed as pretty extreme for OpenAI’s deals, and appreciating that was a game-changer for sentiment.”

A basket of companies connected to OpenAI has gained 74% in 2025, which is impressive but far shy of the 146% jump by Alphabet-exposed stocks. The technology-heavy Nasdaq 100 Index is up 22%.

The skepticism surrounding OpenAI can be dated to August, when it unveiled GPT-5 to mixed reactions. It ramped up last month when Alphabet released the latest version of it Gemini AI model and got rave reviews. As a result, OpenAI Chief Executive Officer Sam Altman declared a “code red” effort to improve the quality of ChatGPT, delaying other projects until it gets its signature product in line.

‘All the Pieces’

Alphabet’s perceived strength goes beyond Gemini. The company has the third highest market capitalization in the S&P 500 and a ton of cash at its disposal. It also has host of adjacent businesses, like Google Cloud and a semiconductor manufacturing operation that’s gaining traction. And that’s before you consider the company’s AI data, talent and distribution, or its successful subsidiaries like YouTube and Waymo.

“There’s a growing sense that Alphabet has all the pieces to emerge as the dominant AI model builder,” said Brian Colello, technology equity senior strategist at Morningstar. “Just a couple months ago, investors would’ve given that title to OpenAI. Now there’s more uncertainty, more competition, more risk that OpenAI isn’t the slam-dunk winner.”

Representatives for OpenAI and Alphabet didn’t respond to requests for comment.

The difference between being first or second place goes beyond bragging rights, it also has significant financial ramifications for the companies and their partners. For example, if users gravitating to Gemini slows ChatGPT’s growth, it will be harder for OpenAI to pay for cloud-computing capacity from Oracle or chips from AMD.

By contrast, Alphabet’s partners in building out its AI effort are thriving. Shares of Lumentum, which makes optical components for Alphabet’s data centers, have more than tripled this year, putting them among the 30 best performers in the Russell 3000 Index. Celestica provides the hardware for Alphabet’s AI buildout, and its stock is up 252% in 2025. Meanwhile Broadcom — which is building the tensor processing unit, or TPU, chips Alphabet uses — has seen its stock price leap 68% since the end of last year.

OpenAI has announced a number of ambitious deals in recent months. The flurry of activity “rightfully brought scrutiny and concern over whether OpenAI can fund all this, whether it is biting off more than it can chew,” Colello said. “The timing of its revenue growth is uncertain, and every improvement a competitor makes adds to the risk that it can’t reach its aspirations.”

In fairness, investors greeted many of these deals with excitement, because they appeared to mint the next generation of AI winners. But with the shift in sentiment, they’re suddenly taking a wait-and-see attitude.

“When people thought it could generate revenue and become profitable, those big deal numbers seemed possible,” said Brian Kersmanc, portfolio manager at GQG Partners, which has about $160 billion in assets. “Now we’re at a point where people have stopped believing and started questioning.”

Kersmanc sees the AI euphoria as the “dot-com era on steroids,” and said his firm has gone from being heavily overweight tech to highly skeptical.

“We’re trying to avoid areas of over-hype and a lot of those were fueled by OpenAI,” he said. “Since a lot of places have been touched by this, it will be a painful unwind. It isn’t just a few tech names that need to come down, though they’re a huge part of the index. All these bets have parallel trades, like utilities, with high correlations. That’s the fear we have, not just that OpenAI spun up this narrative, but that so many things were lifted on the hype.”

OpenAI’s public-relation flaps haven’t helped. The startup’s Chief Financial Officer Sarah Friar recently suggested the US government “backstop the guarantee that allows the financing to happen,” which raised some eyebrows. But she and Altman later clarified that the company hasn’t requested such guarantees.

Then there was Altman’s appearance on the “Bg2 Pod,” where he was asked how the company can make spending commitments that far exceed its revenue. “If you want to sell your shares, I’ll find you a buyer — I just, enough,” was the CEO’s response.

Altman’s dismissal was problematic because the gap between OpenAI’s revenue and its spending plans between now and 2033 is about $207 billion, according to HSBC estimates.

“Closing the gap would need one or a combination of factors, including higher revenue than in our central case forecasts, better cost management, incremental capital injections, or debt issuance,” analyst Nicolas Cote-Colisson wrote in a research note on Nov. 24. Considering that OpenAI is expected to generate revenue of more than $12 billion in 2025, its compute cost “compounds investor nervousness about associated returns,” not only for the company itself, but also “for the interlaced AI chain,” he wrote.

To be sure, companies like Oracle and AMD aren’t solely reliant on OpenAI. They operate in areas that continue to see a lot of demand, and their products could find customers even without OpenAI. Furthermore, the weakness in the stocks could represent a buying opportunity, as companies tied to ChatGPT and the chips that power it are trading at a discount to those exposed to Gemini and its chips for the first time since 2016, according to a recent Wells Fargo analysis.

“I see a lot of untapped demand and penetration across industries, and that will ultimately underpin growth,” said Kieran Osborne, chief investment officer at Mission Wealth, which has about $13 billion in assets under management. “Monetization is the end goal for these companies, and so long as they work toward that, that will underpin the investment case.”

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Air travel across India has been in chaos in the past week after the country’s largest airline, IndiGo, cancelled more than 2,000 flights starting on Friday, stranding thousands of passengers at airports across the country.

The airline, which operates about 2,200 flights a day, has been facing pilot shortages after it failed to adapt to the new pilot rest and duty rules introduced by the government early last year.

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Mass cancellations of flights amid the busy travel season have caused a public outcry, forcing the government to intervene. The airline has been granted exemptions from the new rules, but the disruption has continued, with more than 600 flights cancelled on Sunday.

The airline says operations will be back to normal by December 10-15. The crisis is the biggest blow to the carrier in its 20-year operation.

What is behind the crisis, and what is the government doing to address it?

What we know so far

Starting on December 2, IndiGo flights were delayed and later cancelled due to apparent pilot shortages. Flight disruptions were recorded in Mumbai, Hyderabad and other cities.

On Friday, at least 1,000 flights were cancelled in one of the worst aviation crises in India.

More than 600 flights were cancelled on Sunday, according to the Indian media, despite the government offering exemptions to the private carrier. At least 385 flights were cancelled on Saturday, the fifth day of the crisis.

Thousands of passengers have been stranded at airports across the country due to the air disruption.

The Reuters news agency reported, quoting airport sources, that IndiGo cancelled 124 flights in Bengaluru, 109 in Mumbai, 86 in New Delhi and 66 in Hyderabad on Saturday.

Why did the new flight regulations lead to flight cancellations?

Early last year, the government announced new flight regulations – Flight Duty Time Limitations or FDTL – to improve the working hours of the Indian airlines’ pilots. However, when the November 1 deadline arrived, IndiGo airline was not prepared. As a result, it was first forced to delay and later cancel flights, as there were not enough pilots available.

FDTL was finally implemented in two phases this year, with the second phase coming into effect on November 1. The rules include:

• Increasing pilots’ mandatory weekly rest period from 36 to 48 hours. A pilot’s personal leave request, however, cannot be included under the mandatory rest period.
• Capping pilots’ flying hours that continue into the night to 10 hours.
• Capping the weekly number of landings a pilot can make between midnight and early morning to two.
• Submitting quarterly pilots’ fatigue reports to India’s aviation regulator – the Directorate General of Civil Aviation (DGCA).

Aviation experts and pilot unions have said IndiGo has been the hardest hit due to negligence and a lack of planning for the new rules.

“Despite the two-year preparatory window before full FDTL implementation, the airline inexplicably adopted a hiring freeze, entered non-poaching arrangements, maintained a pilot pay freeze through cartel-like behaviour, and demonstrated other short-sighted planning practices,” the Federation of Indian Pilots told the Press Trust of India news agency on December 4.

Former AirAsia CFO Vijay Gopalan blamed IndiGo’s “very very lackadaisical, nonchalant attitude” in adapting to the new rules as a reason for the crisis.

What steps has the government taken to address the crisis?

The government has ordered a high-level inquiry to determine the reasons and accountability for flight disruptions.

Civil Aviation Minister Kinjarapu Rammohan Naidu blamed IndiGo for “mismanagement regarding their crew”, adding that other airlines were prepared for the changes.

The government on Friday announced exemptions from the new rules for the carrier and provided stranded passengers with train tickets to continue their journey.

IndiGo has been exempted until February 10 from the requirement to cap the weekly number of landings for a pilot between midnight and early morning. It has also been exempted from the pilots’ flight duty time.

The Airline Pilots Association of India has, however, protested against the exemptions, saying the rules “exist solely to safeguard human life”.

On Saturday, India’s aviation watchdog, the DGCA, sent a letter to IndiGo CEO Pieter Elbers, warning him of regulatory action amid flight cancellations.

“You have failed in your duty to ensure timely arrangements for conduct of reliable operations,” Reuters reported, quoting DGCA official Ravinder Singh Jamwal.

The Ministry of Civil Aviation on Saturday also announced capping of airfares to control the surge in ticket prices due to a breakdown in IndiGo’s flight services.

When will the IndiGo operations return to normal?

Acknowledging its failure to adapt to the new rules, IndiGo has apologised for the serious “operational crisis”. It attributed the mass cancellations to “misjudgement and planning gaps”.

IndiGo CEO Pieter Elbers said in a video statement on Friday that it would “take some time” for the flight operations to get back to normal.

“Given the size, scale, and complexity of our operations, it will take some time to return to a full normal situation, which we anticipate between 10 and 15 December,” he said in the video.

In his message, Elbers announced that the airline has three lines of action to address the crisis, which include customer support measures to effectively communicate cancellations and refunds, aligning with the DGCA’s regulations.

The airline on Sunday afternoon said it is on track to operate more than 1,650 flights, up from 1,500 on Saturday. It added that 137 out of 138 destinations are in operation. Full waiver on cancellations and reschedule requests for bookings until December 15 will be given, it said.

Message from Pieter Elbers, CEO, IndiGo. pic.twitter.com/bXFdqoB0Q2

— IndiGo (@IndiGo6E) December 5, 2025

How are other leading Indian airlines managing?

Other Indian carriers, including Air India and Akasa Air, continue with their operations amid the chaos.

According to Indian media reports, Mumbai-based low-cost carrier Akasa Air, focused on recruiting new pilots, which helped it adapt to the new FDTL norms.

A report by Indian business portal Money Control noted that Tata-owned Air India also boosted flight crew for domestic flights, helping it better handle the new rules.

However, international flights by Air India and its sister company, budget carrier Air India Express, have reduced international flight operations to undertake more safety checks after a deadly June plane crash that killed 241 people in Gujarat state.

Has the crisis impacted airfare?

Yes. With IndiGo dominating the Indian aviation market, other airlines have hiked prices on many routes, especially return flights from metro cities New Delhi, Mumbai and Bengaluru.

“That wasn’t pricing. It was profiteering. When systems collapse, the market becomes a vulture,” posted an X user after ticket prices soared.

According to Indian media reports, the Civil Aviation Ministry has warned airlines that it has “taken a serious note of unusually high airfares being charged by certain airlines during the ongoing disruption” and has in turn “invoked its regulatory powers to ensure fair and reasonable fares across all affected routes.”

As per a Reuters report, the government has said flight journeys between 1,000km and 1,500km (620-930 miles) should be capped at 15,000 rupees ($167).

Airfares were previously capped in India in May 2020, during the COVID-19 pandemic, when the subcontinent ordered lockdowns and reduced flight operations. According to a study published last November by global trade association Airports Council International (ACI), India, however, saw a 43 percent rise in domestic fares in the first half of 2024 compared with 2019.

So far, Air India and Air India Express, which hold 26 percent of the market share, have addressed the situation and clarified that “economy class airfares on non-stop domestic flights have been proactively capped to prevent the usual demand-and-supply mechanism being applied by revenue management systems”.

The two airlines added that they are seeking to add capacity to help travellers and their baggage reach their final destinations efficiently.

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Threats relating to technology, disinformation, economic security and foreign interference are overshadowing traditional security concerns in Australians’ minds, according to data released by the Australian National University National Security College.

More than 12,000 people were asked across two surveys, in November last year and July this year, to rate the seriousness of 15 potential threats over the next decade.

Combining the categories of “major” and “moderate” the five most serious concerns were rated in July 2025 as:

• the use of artificial intelligence to attack Australian people and businesses (77%)

• a severe economic crisis (75%)

• disruption to critical supplies due to a crisis overseas (74%)

• the deliberate spread of false information to mislead the Australian public and harm their interests (73%), and

• a foreign country interfering in Australia’s politics, government, economy or society (72%).

Climate change rated sixth (67%), although a high proportion of people (38%) rated it as a “major” threat. This was second only to threats relating to AI (40%).

The possible threat of Australia being involved in military conflict came in seventh (64%).

Anxiety about security issues is increasing. In July half the respondents agreed with the statement “I am worried about Australia’s national security”. This was an 8% rise between November 2024 and July.

Over that time, threat perceptions increased across all 15 possible threats that were asked about.

The table below shows the threat perceptions of about 6000 Australians in July.

Threat Perceptions July 2025

The November 2024 research also asked, from a list of four, what Australians want to nation to prioritise in the next five years.

The leading priority was safe and peaceful communities, nominated by 35%. When second preferences are included, this rises to 64%.

This priority ranked top across a wide range of demographics, including age, gender, cultural background, education , income and location.

The survey found three other national priorities rated in this order:

.. increasing Australia’s economic prosperity (26%)

.. upholding Australia’s democratic rights and freedoms (23%)

.. strengthening Australia’s security (15%).

The research also included more than 300 interviews across Australia.

The consultations found national security was “consistently framed as being about the peaceful continuity of everyday life”.

National priority for the next 5 years (%)

NSC head Professor Rory Medcalf said: “On the one hand, Australians know what they want to protect, especially in terms of peace, safety, community, democracy and prosperity, On the other hand, they recognise that a complex set of rapidly emerging threats can put these cherished priorities at risk.”

The full research results will be released early next year.

The ANU National Security College is a joint initiative of the federal government and the university.

The College undertook the community consultations as an independent research initiative.

Chemotherapy-free approaches could offer comparable efficacy with less toxicity

ORLANDO, Fla., Dec. 7, 2025 /PRNewswire/ — Targeted therapies and immunotherapies are increasingly offering viable alternatives to the chemotherapies that have stood for decades as a mainstay of treatment for individuals living with blood cancers, according to studies presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.

“These studies point to the departure of traditional chemotherapy and shedding traditional approaches,” said Laura Michaelis, MD, professor of medicine at the Medical College of Wisconsin in Milwaukee, who moderated the press briefing Emerging Therapies and Immunotherapies in Blood Cancers. “Researchers are focused on therapeutic approaches that can offer the same or better responses with less toxicity – meaning fewer early deaths, less organ damage, and better quality of life for patients.”

In the first study, a combination regimen of azacitidine and venetoclax led to better responses and improved event-free survival in patients who were fit enough to undergo conventional induction chemotherapy for newly diagnosed acute myeloid leukemia. The results suggest the combination can lead to better outcomes with substantially less hospitalization and a lower symptom burden for patients with intermediate-to-high-risk disease.

The second study reports that a chemotherapy-free combination of epcoritamab, a bispecific antibody, and rituximab and lenalidomide, an immunotherapeutic combination, brought a robust and lasting response, showing promise as a chemotherapy alternative for patients with relapsed or refractory follicular lymphoma.

The third and fourth studies reflect the expanding role of tyrosine kinase inhibitors, which target particular enzymes to inhibit cancer cell growth. One study suggests a non-covalent Bruton tyrosine kinase (BTK) inhibitor, pirtobrutinib, may offer equivalent or better outcomes compared with the older covalent BTK inhibitor, ibrutinib, for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma. The final study – focused on a combination therapy that included ponatinib, a tyrosine kinase inhibitor, and blinatumomab, an immunotherapy – offers evidence that chemotherapy can be omitted from frontline treatment for Ph+ acute lymphoblastic leukemia without sacrificing efficacy or safety.

Azacitidine–Venetoclax Combination Outperforms Standard Care in Acute Myeloid Leukemia Patients Eligible for Intensive Chemotherapy
6: Results from paradigm – a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia  

In a new trial, patients newly diagnosed with acute myeloid leukemia (AML) fared significantly better with a combined regimen of azacitidine and venetoclax compared with conventional induction chemotherapy. The azacitidine–venetoclax combination (known as aza-ven) is the standard of care for older adults who are not fit enough for intensive chemotherapy. The trial is the first to test the superiority of this regimen to intensive induction chemotherapy, the current standard for fit patients.

“Our study met its primary endpoint, demonstrating that aza-ven improves event-free survival. It also leads to higher rates of overall response and composite complete response than intensive induction chemotherapy in younger, intensive-chemotherapy-eligible patients,” said lead study author Amir Fathi, MD, director of the Center for Leukemia at Mass General Brigham Cancer Institute and associate professor of medicine at Harvard Medical School in Boston. “A greater proportion of patients successfully proceeded to transplant following response with less early mortality, significantly improved quality of life during initial treatment, and less time in the hospital.”

AML is a cancer of the bone marrow that causes an overabundance of abnormal white blood cells and impedes the production of healthy blood cells. Hematopoietic stem cell transplantation can cure AML, but this option is not available to everyone, and almost all patients must undergo initial treatments to reduce cancer in the bone marrow before proceeding to transplant. Intensive induction chemotherapy with cytarabine and anthracyclines has long stood as the standard frontline treatment, but this treatment requires patients to spend about a month in the hospital and carries a high risk of infection, bleeding, and other complications and side effects.

Azacitidine is a chemotherapy drug that has been used for years, in injectable forms, for older patients with AML. Venetoclax is an oral targeted therapy that inhibits the BCL-2 protein, which is involved in cancer cell survival. The two agents are generally well tolerated and can be administered and managed safely on an outpatient basis over time.

In the trial, 172 adult patients were randomly assigned to receive either aza-ven or standard intensive induction chemotherapy. The results were significantly better in the aza-ven arm for the trial’s primary endpoint, event-free survival (EFS), with events defined as relapse, disease progression, disease refractoriness prompting change in therapy, or death. With a median follow-up of just under 22 months, EFS was significantly longer in the aza-ven arm; the median EFS was more than 14 months among those receiving aza-ven compared with a median of just over six months for those receiving induction chemotherapy. The effect of aza-ven remained protective even after adjusting for other variables, and at one year, 53% of those in the aza-ven arm met criteria for EFS compared with 36% of those in the control arm. 

Patients whose cancer had certain characteristics, including core binding factor fusions, FLT3 mutations, or NPM1 mutations (unless age 60 or over), were excluded from the trial. As a result, the study reflects a patient population of predominantly intermediate-to-high-risk AML, although all patients were fit enough to undergo intensive induction chemotherapy.

“I believe the data support the use of this treatment in this population,” said Dr. Fathi. “It applies to adverse risk and intermediate risk patients who don’t have FLT3 mutations. That doesn’t mean that other patient populations may not benefit, but they require their own focused study.”

Participants receiving aza-ven experienced a higher overall response to treatment than those receiving induction chemotherapy, with 88% of those in the aza-ven arm seeing an overall response and 78% seeing a composite complete response, compared with 62% and 54% in the control arm, respectively. They were also more likely to progress to a transplant, which occurred in 61% of those receiving aza-ven and 40% of those receiving induction chemotherapy.

The rate of grade 3 or 4 therapy-related adverse events was similar between study arms. No patients who received aza-ven died within 60 days, while 5% of those in the control group died by this timepoint. Hospitalization was also longer among patients in the control group. Ten percent of patients in the induction arm required admission to the intensive care unit during their index hospitalization, compared with zero in the aza-ven arm. Patients in the aza-ven arm also reported a lower symptom burden and lower rates of depression at two weeks, according to quality of life assessments.

The researchers plan to conduct further analyses to compare costs, the rate of infectious complications, and other factors that may inform treatment decisions for this patient population. In addition, they will assess the use of measurable residual disease status to provide key prognostic and predictive information across arms of the study and inform the optimal amount of treatment needed for aza-ven prior to transplant. 

The study was investigator-initiated; Genentech and AbbVie Inc. (maker of venetoclax), provided the study drug and funding to support research staff.

Amir Fathi, MD, of Mass General Brigham Cancer Institute and Harvard Medical School will present this study on Sunday, December 7, 2025, at 3:45 p.m. Eastern time during the Plenary Scientific Session in West Hall D2 of the Orange County Convention Center.

Adding Epcoritamab to Standard Second-Line Therapy Improves Follicular Lymphoma Outcomes
466: Primary Phase 3 results from the epcore FL-1 trial of epcoritamab with rituximab and lenalidomide (R2) versus R2 for relapsed or refractory follicular lymphoma  

In a new trial, patients with follicular lymphoma had a significantly higher response to treatment and a nearly 80% reduction in the risk of death or disease progression if they received epcoritamab in addition to the standard second-line regimen versus the standard regimen alone. The study is the first reported randomized controlled trial to test a bispecific antibody combination in follicular lymphoma and suggests the combination could offer an effective alternative to chemotherapy that can be safely administered on an outpatient basis.

Based on the study results, the U.S. Food and Drug Administration (FDA) approved epcoritamab with rituximab and lenalidomide for relapsed or refractory follicular lymphoma in November 2025.

“The addition of epcoritamab to rituximab and lenalidomide very substantially increased the response rates, depth of response, and duration of benefit and therefore may represent a new standard of care in patients with follicular lymphoma,” said lead study author Lorenzo Falchi, MD, assistant attending physician in the lymphoma service at Memorial Sloan Kettering Cancer Center in New York. “We are at a point in time when chemo-free approaches based on immunotherapy can seriously challenge chemotherapy as the standard of care. We will not know for a long time if [this regimen] is curative, but it’s certainly the beginning of a bright era for chemo-free therapy for follicular lymphoma.”

Follicular lymphoma is a slow-growing non-Hodgkin lymphoma that can progress to a more aggressive form. Patients who see their cancer return after an initial round of treatment have limited options and often experience subsequent relapses.

The immunotherapeutic combination rituximab and lenalidomide (known as R2) has become a standard second-line treatment for follicular lymphoma, while epcoritamab, a bispecific antibody, was more recently approved for follicular lymphoma that is relapsed or refractory (R/R) after two or more lines of systemic therapy. R2 and epcoritamab operate through different mechanisms to enhance the ability of a patient’s immune system to recognize and eradicate cancer cells.

The study randomized 488 patients with R/R follicular lymphoma to receive epcoritamab plus R2 or R2 alone for up to 12 cycles. At a median follow-up of just under 15 months, the group receiving epcoritamab plus R2 showed a significantly higher overall response rate (95.1% versus 79.2% among the control group) and a significantly longer progression-free survival (85.5% versus 40.2% at 16 months), meeting both of the trial’s primary endpoints.

Epcoritamab plus R2 also outperformed R2 alone for the trial’s secondary endpoints, with 82.7% of patients in this arm seeing a complete response (CR) to treatment versus 49.8% among those who received R2 alone. Participants who received epcoritamab plus R2 also showed a significantly longer duration of response and CR. The results were consistent across all subgroups analyzed.

Additionally, researchers noted that very few patients who received epcoritamab required subsequent treatments during the study period, suggesting that the new regimen can help patients avoid or delay further treatments and their associated toxicities. At 16 months, 92.8% of patients in this group remained free from new anti-lymphoma treatments, compared with 64.9% among those who received R2 alone.

“A time-limited therapy that is not followed by another therapy for a long time is certainly a very good value for patients,” said Dr. Falchi.

Participants who received epcoritamab plus R2 experienced a higher rate of adverse events, with grade 3 or 4 treatment-related adverse events occurring in 90.1% of patients receiving epcoritamab and 67.6% of patients in the control group. This increase was driven largely by a higher rate of low white blood cell counts and infections among those receiving epcoritamab. There was no evidence of neurological toxicity and no reports of grade 3 or 4 cytokine release syndrome (CRS). According to researchers, this suggests that the combined regimen is safe to administer in a variety of medical settings.

“There has been some hesitancy to use bispecific antibodies in a community setting because of CRS,” said Dr. Falchi. “The prospect of a subcutaneous, completely outpatient treatment that does not result in a significant rate of CRS is good news for giving more patients the best opportunity for a response.”

The study also tested two different step-up dosing regimens for the epcoritamab–R2 combination, showing that three initial smaller doses resulted in a reduced rate of low-grade CRS compared with a course of just two initial smaller doses.

Given the study’s relatively short median follow-up time to date, the researchers will continue to track participants to assess longer-term outcomes. In addition, a separate study is underway to test the epcoritamab–R2 combination in a frontline setting. Dr. Falchi added that epcoritamab could also be investigated as a single-agent treatment for patients who are not candidates for R2.

The study was funded by Genmab and AbbVie Inc. The results were simultaneously published in the Lancet.

Lorenzo Falchi, MD, of Memorial Sloan Kettering Cancer Center, will present this study on Sunday, December 7, 2025, at 10:15 a.m. Eastern time in West Hall D2 of the Orange County Convention Center.

Non-Covalent BTKi Pirtobrutinib Shows Promise as Frontline Therapy for CLL/SLL
683: Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor   

Pirtobrutinib, a non-covalent Bruton tyrosine kinase (BTK) inhibitor, met the primary endpoint for non-inferiority in terms of overall response rate in the first head-to-head comparison with ibrutinib, a covalent BTK inhibitor. Based on the study results, researchers suggest pirtobrutinib shows promise as initial BTK inhibitor therapy, including in the frontline setting, for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Non-covalent BTK inhibitors were initially developed to overcome resistance to covalent BTK inhibitors. This study is the first phase III clinical trial to directly compare a non-covalent BTK inhibitor to a covalent BTK inhibitor in patients with CLL or SLL. It included patients who had not received any previous treatment, a first for any phase III study directly comparing BTK inhibitors, as well as patients who had their cancer come back (relapse) or not respond (refractory) after receiving treatments other than a covalent BTK inhibitor.

“Pirtobrutinib was clearly non-inferior to ibrutinib, and the response rate actually favors pirtobrutinib in the total cohort,” said lead study author Jennifer Woyach, MD, Bertha Bouroncle, MD, and Andrew Pereny, chair of medicine at The Ohio State University College of Medicine. “This shows that pirtobrutinib is a reasonable choice in both the treatment-naive and relapsed/refractory settings.”

CLL and SLL are slow-growing forms of non-Hodgkin lymphoma that develop when lymphocytes grow out of control and abnormal B cells build up in bone marrow (CLL) or lymph nodes (SLL). BTK inhibitors work by blocking the BTK enzyme, which plays a role in B-cell growth and proliferation.

The study enrolled 662 adult patients with CLL or SLL. Of these, 225 had not received any prior treatments, and 437 were R/R to prior treatments and had not received any BTK inhibitors. Participants were randomly assigned to receive either pirtobrutinib or ibrutinib and remain on their assigned therapy unless their disease progressed or they experienced unacceptable side effects.

The study’s primary endpoint, non-inferiority of pirtobrutinib for overall response rate (ORR), was achieved in the full study population. Of 662 participants, the ORR was 87.0% among those receiving pirtobrutinib and 78.6% among those receiving ibrutinib. The results consistently favored pirtobrutinib across the majority of subgroups, including those who were treatment-naive, relapsed/refractory (R/R) to prior treatments, and those with various high-risk disease characteristics.

Survival without disease progression, the study’s secondary endpoint, will be formally assessed at a later time. Early results suggest that pirtobrutinib may offer some benefit over ibrutinib for this endpoint as well, showing 18-month progression-free survival (PFS) rates of 86.9% in the pirtobrutinib arm and 82.3% in the ibrutinib arm. Preliminary results suggest treatment-naive participants saw the most pronounced benefit for this endpoint.

“The PFS is still a little bit immature at this point, but trends toward favoring pirtobrutinib in all of the groups – in the total cohort, in the R/R group, and, importantly, in the treatment-naive cohort,” said Dr. Woyach. “That’s really important, because given the safety of pirtobrutinib, it suggests that this might be a good option in the future for some patients with frontline CLL/SLL.”

The rates of treatment-emergent adverse events (AEs) and treatment discontinuation due to AEs were overall similar between arms. However, those receiving pirtobrutinib experienced lower rates of AE-related dose reductions, treatment discontinuation due to progressive disease, and certain cardiovascular AEs including hypertension and development of atrial fibrillation or flutter.

These results may indicate pirtobrutinib is especially suitable for use in older or more frail patients. “While the efficacy and safety of pirtobrutinib have been very clearly established when given after a covalent BTK inhibitor, there are likely going to be subgroups of patients where pirtobrutinib is a more attractive option instead of the covalent BTK inhibitors,” said Dr. Woyach.

In addition to continuing to track outcomes from this study, Dr. Woyach said that future clinical trials could help refine the use of pirtobrutinib alone or in combination with other therapies as a frontline treatment. She added that researchers are also continuing to investigate possible mechanisms through which cancer may become resistant to non-covalent BTK inhibitors to further optimize treatment strategies.

This study was funded by Eli Lilly and Company, maker of pirtobrutinib. The results were simultaneously published in the Journal of Clinical Oncology.

Jennifer Woyach, MD, of The Ohio State University College of Medicine, will present this study on Sunday, December 7, 2025, at 5:30 p.m. Eastern time in W224ABEF of the Orange County Convention Center.

New Findings Support a Chemo-Free Approach for Treating Ph+ ALL
439: First results of the Phase III GIMEMA ALL2820 trial comparing ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adult ph+ acute lymphoblastic leukemia patients   

A chemotherapy-free combination treatment outperformed a combination of targeted therapy and chemotherapy among patients with Ph+ acute lymphoblastic leukemia (ALL) in a new study. The phase III trial, which included adult patients with no upper age limit, is the first formal comparison of the efficacy and safety of these two approaches in newly diagnosed patients with Ph+ ALL.

Researchers say the findings offer reassurance that chemotherapy can be omitted without detrimental effects and suggest that a chemo-free targeted agent and immunotherapy combination could become the new standard of care for this patient group.

“The chemo-free approach significantly reduced the rate of death in addition to increasing the rate of complete remission,” said lead study author Sabina Chiaretti, MD, associate professor at Sapienza University of Rome in Italy. “The significance was very impressive, a more than 20% difference in terms of molecular response achievement [a sensitive test for residual cancer cells following treatment], so this approach truly is better.”

ALL is a fast-growing type of leukemia affecting white blood cells, while Ph+ ALL is a genetic subtype characterized by the causal genetic abnormality in the Philadelphia chromosome. Patients with Ph+ ALL have historically faced a poor prognosis and increased resistance to chemotherapy, pointing to a need for improved treatments. In recent years, targeted tyrosine kinase inhibitors (TKIs) and immunotherapies have brought promising results, with good efficacy and fewer side effects than chemotherapy. Researchers have sought to identify the optimal combination of therapies among TKIs, immunotherapies, and chemotherapy. 

For the trial, researchers enrolled 236 adult patients with Ph+ ALL, ranging in age from 19 to 84 years. Two-thirds of participants were randomly assigned to the experimental arm and received a TKI plus immunotherapy; one-third were assigned to the control arm and received a TKI plus chemotherapy. Patients in the experimental group received an initial course of steroids, a 70-day induction with the TKI ponatinib, and two to five cycles of the immunotherapy blinatumomab. Patients in the control group received the TKI imatinib along with either four or six cycles of chemotherapy for patients older or younger than age 65, respectively.

Patients in the chemo-free experimental arm had a significantly higher rate of event-free survival and a better response to treatment. At a median follow-up of 23 months, event-free survival was 87% in the experimental arm and 71% in the control arm, while the rate of death was 3.5% in the experimental arm and 10% in the control arm. The relapse rate was similar among arms (6% in the experimental group and 8% in the control group), although about half of the relapses in the experimental group occurred in patients who had discontinued their treatment.

Complete remission was achieved in 94% of those in the experimental arm and 79% of those in the control group. The chemo-free treatment regimen also resulted in a higher rate of negative measurable residual disease (MRD) status, an indicator that all or nearly all cancer cells have been eradicated. While only 49% of those in the control group achieved MRD-negative status, 71% of those in the experimental group achieved MRD-negative status after two cycles of blinatumomab, and 80% reached this status after five cycles. 

“The more cycles with blinatumomab, the more the molecular remission rate increased,” said Dr. Chiaretti. “This suggests that patients really should receive the planned five cycles. This is important because we have been working with blinatumomab for years, but we did not yet know how many cycles should be recommended.”

Participants randomized to the control group were offered the option to cross over to the experimental arm if their disease was MRD-positive. About 37% of patients in the control arm eventually received the experimental treatment regimen, and 62% of these patients subsequently achieved MRD-negative status.

Most of the deaths occurred in older patients, and infections were a primary cause of death among those that occurred in the experimental arm. The safety profiles were consistent with those expected for each therapy involved in the study, and researchers said that most adverse events were successfully addressed by reducing dosage.

While the study was conducted exclusively in Italy, Dr. Chiaretti noted that the results should be applicable in any country. She added that a chemo-free treatment approach can bring economic benefits by reducing the need for hospitalization and allowing patients to continue working while undergoing cancer treatment.

A separate study is now underway to determine whether patients with sustained MRD-negative status can discontinue TKI treatment without raising the risk of a relapse.

Sabina Chiaretti, MD, of Sapienza University of Rome, will present this study on Sunday, December 7, 2025, at 9:30 a.m. Eastern time in W224A-F of the Orange County Convention Center.

The American Society of Hematology (ASH) (hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. Since 1958, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. Join the #Fight4Hematology by visiting hematology.org/fight4hematology.

The Blood journals (https://ashpublications.org/journals) are the premier source for basic, translational, and clinical hematologic research. The Blood journals publish more peer-reviewed hematology research than any other academic journals worldwide.

SOURCE American Society of Hematology