Latest news with #Voorhees
Medscape
2 days ago
- Health
- Medscape
OS Data From CARTITUDE-1: A Cure for Myeloma?
CHICAGO — The anticipated release of 5-year overall survival (OS) data from the CARTITUDE-1 trial showed that the use of ciltacabtagene autoleucel (cilta-cel) in patients with relapsed or refractory multiple myeloma (RRMM) met or exceeded expectations. 'We already knew from our initial publication that 98% of patients who got cilta-cel responded to therapy and that the majority of those responses were complete responses. We also knew that the median PFS [progression-free survival] was approximately 34 months, which is unheard of in this patient population,' said study author Peter Voorhees, MD, of Atrium Health/Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, North Carolina, during an oral abstract session at the American Society of Clinical Oncology (ASCO) 2025 annual meeting. 'Today we are sharing that the median OS is just over 5 years, and that one third of the study population has remained progression-free following a single cilta-cel infusion with no maintenance therapy.' These findings were simultaneously published in the Journal of Clinical Oncology . CARTITUDE-1 is a phase 1B/2 trial in which 97 patients with four or more prior lines of treatment for RRMM received cilta-cel. Of these patients, 45 are currently alive and in long-term follow-up in the CARTinue 15-year post-infusion study. This group is further broken down among 32 patients who have remained progression-free since their infusion and 13 patients who had progressive disease and are now in post-progressive disease follow-up. Of the progression-free patients, 12 from a single center with annual minimal residual disease (MRD) testing remain MRD-negative at year 5 or longer. Voorhees noted that long-term remissions were not limited to patients with standard-risk disease. 'Patients with high-risk cytogenetics like del17p, t(14;16) or t(4;14) and those with extramedullary plasmacytomas were equally likely to be progression-free,' he said. The study team also found that patients in long-term remission had more immune-fit drug products and higher effector to target ratios at peak expansion, Voorhees said. The discussant for this study, Krina K. Patel, MD, MSc, of MD Anderson Cancer Center in Houston told attendees that the CARTITUDE-1 OS data were 'phenomenal for these hard-to-treat patients' as she reshared Voorhees' PFS slide showing a plateau extending toward 78 months. 'I do hope this plateau continues forever for these 33% of patients, to the point where we can say it's a true cure,' Patel said. 'But I don't hold my breath because most of my patients do relapse at some point.' Patel also noted the limitation that CARTITUDE-1 is a single-arm study. 'We know there's CARTITUDE-4, so we have randomized data that shows better performance than at least a couple of our standard care options,' she said. 'But it is hard to compare historical controls.' Following this presentation, Voorhees sat down with Medscape Medical News . The following interview has been edited for clarity. Since FDA approval of cilta-cel was based on CARTITUDE-1, the expectation was that longer-term data would also be very good. Why are these long-term OS results from CARTITUDE-1 so important? The median overall survival wound up being just over 5 years, when we would have expected it to be 1 year in a similar population. One third of the patients are alive and in remission, and they've been off therapy for 5 years, which is something we've never seen before. Just as importantly, we're not seeing new safety signals, and the rates of high-grade infection seem to be declining further out from treatment, which is what we would expect with immune recovery. Is it time to start thinking of myeloma as a potentially curable disease? I'm always very cautious when I discuss that. Possibly there may be patients who never relapse, but I am curious to see how these next 5 years play out because if the majority of these patients remain in remission 10 years out from cilta-cel infusion, then I'll be using the word 'cure' less cautiously at that time. We do talk a lot about functional cures in multiple myeloma: For someone newly diagnosed with standard-risk disease, they will get a three or four drug induction therapy, then a transplant followed by maintenance therapy. A lot of these patients will stay in remission well beyond 10 years and they'll pass away at an older age of unrelated causes. What do the new CARTITUDE-1 data do to the paradigm of continuous therapy? The other thing that has made us hesitate about using the word 'cure' in myeloma is the traditional paradigm of continuous treatment. What happens to patients in remission when you stop therapy? Are they in a long-term remission because you're keeping the heat on the disease or are they cured and what you're applying to them continuously is unnecessary? What makes the cilta-cel 5-year data so compelling is that these patients got that single infusion and a third of them are still in remission 5 years later. Your ASCO presentation included a discussion of MRD level at 10−5 vs 10−6. Why is that important here? Currently the best that's available as far as regular clinical practice is concerned is a 10−6 but MRD negativity is often reported at 10−5. But as so many people going through CAR T-cell therapy achieve MRD negativity at 10−5, the 10−6 level of sensitivity seems to be a better way of distinguishing those patients that might be at higher risk for disease progression vs those that are not. You're going to see us transitioning more toward using MRD negativity at 10−6 for our clinical trials going forward. What's ahead for the CARTITUDE research program? The expectation is the earlier you use a highly effective therapy, the better it's going to perform. We have the CARTITUDE-4 study, which compares cilta-cel with standard of care in both standard-risk and high-risk disease. CARTITUDE-5 and CARTITUDE-6 are both phase 3 studies looking at the application of cilta-cel therapy for newly diagnosed myeloma patients. For CARTITUDE-5, we're looking to see if adding cilta-cel after lenalidomide, bortezomib and dexamethasone will improve outcomes for patients not eligible to receive an upfront transplant. And in CARTITUDE-6, we're looking to see if cilta-cel can be used instead of autologous stem cell transplantation as consolidation for younger, fitter patients with newly diagnosed myeloma. And if things go the way we expect them to, we may be starting to use that word cure more often. When did it really hit you that the cilta-cel data are better than anything else that has yet happened? We've got several patients from CARTITUDE-1 at our institution who are still in complete remission, and they've lived a normal life for years now. We have patients on the CARTITUDE-2 program who are also long-term responders, so we see this in our everyday practice more and more. If you had told me 10 years ago that this is what we would be doing, I would've thought there's no way. But here we are doing it. This study was funded by Johson & Johnson and Legend Biotech. Voorhees disclosed having relationships with Abbvie/Genentech, Ascentage Pharma, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Indapta Therapeutics, Janssen, Kite (a Gilead company), Nektar, Pfizer, Regeneron, Sanofi, and TeneoBio. Patel reported ties with Abbvie, AstraZeneca, Bristol-Myers Squibb, Celgene, Janssen, Legend Biotech, Merck, Novartis, Pfizer, Regeneron, and Takeda.
Boston Globe
23-05-2025
- Entertainment
- Boston Globe
‘Jaws' is turning 50. To celebrate, we followed the shark's second victim around Martha's Vineyard.
Get Starting Point A guide through the most important stories of the morning, delivered Monday through Friday. Enter Email Sign Up The "Jaws" movie poster. Advertisement ' ' Jaws' really put Martha's Vineyard on the map,' says Ashton. 'We wanted to do something really spectacular to honor it.' There will be special screenings, talks, and parties, during Jaws 50th Anniversary (June 20-22) and during the following Amity Week, June 22-29 (see sidebar for more information), but also a variety of summer and yearlong activities. The onetime Broadway play " Jaws," will run from July 5-20 at Martha's Vineyard Performing Arts Center. The new Advertisement Sheriff Brody's house has been renovated since the movie was filmed. It's where Brody's wife screams to their son, 'Did you hear your father? Get out of the water!' Pamela Wright We spent a few days on the island, visiting movie sites and exploring all things related to the movie. Even if you're not a 'Jaws' fan, it's a great way to see the island and its most picturesque and historic spots. DIY-ers can download the SetJetters' free film tourism app, for a list and map of " Jaws" scenes on the island, or hop on one of the specialty tours, like the Jeffrey Voorhees, the actor who played 12-year-old Alex Kintner, the second victim in the movie, leads "Jaws" tours of Martha's Vineyard for the HomeGrown tour company. He shares photos, movie insights, and stories with tour participants as they travel around the island, visiting movie sites. Pamela Wright We took the Steamship Authority ferry from Woods Hole to Vineyard Haven and checked into the family-owned and welcoming " Jaws" events and other activities on the island. Martha's Vineyard Museum is also a short stroll from the hotel. As advised, we didn't bring a car and found it easy and efficient to get around by bus. And all buses are free this year in honor of the " Jaws" anniversary. Advertisement Aquinnah Cliffs is a popular and ultra scenic destination on Martha's Vineyard. Nearby is where the Welcome to Amity sign appeared in the movie "Jaws." Pamela Wright 'Get out of the water!' 'I died when I was 12,' Jeffrey Voorhees said as he greeted us in the lobby of the Mansion House. Voorhees agreed to give us a " Jaws" tour of the island, and a behind-the-scenes look at the production. Many locals took part in the filming of "Jaws." Many were hired as extras earning $40 a day. 'Everyone we knew was in that movie,' Voorhees explained. 'Most were hired as extras earning $40 a day.' Voorhees got called back for a speaking part, making $140 a day, and because he signed a SAG agreement, he continues to earn royalties. He also has a website selling signed merchandise (how about a blood-splattered raft with a shark bite out of it?), does Cameo greetings, and travels to special events and festivals to do signings. He still receives postcards in the mail from fans: Thinking of you, dead another year! On Martha's Vineyard, he's a bit of a celebrity. 'Hey Vintner! Be dead already!' a man walking his dog shouted at us as we stood in front of the Telegraph Hill Lighthouse in East Chop, our first stop on our 'Jaws' tour. Around the corner was Sheriff Brody's house (much of it replaced). Voorhees explained that this is where Brody's wife infamously screams to their son, 'Did you hear your father? Get out of the water!' There were no sharks lurking, only pretty views of Vineyard Haven Harbor and Vineyard Sound. Advertisement Nothing much has changed in the tiny fishing village of Menemsha on Martha's Vineyard since scenes for "Jaws" were filmed there in 1974. Pamela Wright Amity Island welcomes you Our next stop was Aquinnah Cliffs, with an expansive green space, a lighthouse, and striking, lofty views of the Atlantic Ocean. 'This is where the 'Welcome to Amity' sign was,' said Voorhees. 'It had one scene in the movie, but everyone likes coming out here.' Why not? It's beautiful, and we stayed awhile to take in the views. Voorhees told more stories as we headed into the small fishing village of Menemsha. The mechanical shark, he told us, was designed for freshwater and kept breaking down. 'My friends and I knew where it was stored in the back of an old, beat-up warehouse,' he said. 'We used to climb all over that thing.' Not everyone on Martha's Vineyard appreciated the filming. It caused congestion and inconvenience, and it was smelly for days. Remember the tiger shark that was dissected? 'It was a real shark that they hung up by the docks in Edgartown,' Voorhees says. 'It stunk up the whole town. The local fishermen dumped a pile of fish carcasses at Spielberg's rental house as a payback.' The movie put Martha's Vineyard on the map, and the island has been identified with it ever since. It is home to many shark references. Pamela Wright In Menemsha, we looked for cans of Crush It Like Quint Narragansett beer (reportedly the company is selling crushable cans in honor of the 50th anniversary), but settled for a You're Gonna' Need a Bigger Boat T-shirt and an Amity Island ball cap. We strolled the tiny, stuck-in-time village, and watched as fishing boats chugged in and out of the harbor. 'Nothing has changed since they filmed here,' Voorhees pointed out. 'It looks exactly the same.' Advertisement 'This is where I died' Many of the movie's filming sites were in Edgartown, an affluent, classic island village. We walked the village streets, lined with historic buildings, now housing shops and restaurants as Voorhees pointed out movie sites. The Edgartown Town Hall that served as Amity Town Hall in the movie looks the same inside and out. We went inside to see where Quint scratched his fingernails on the blackboard during the town meeting. We also stopped at the Rockland Trust Bank to see the Amity National Bank sign that was used in the movie. Voorhees pointed out the hardware store (now the Port Hunter restaurant), the Chappy ferry, the hoist where the tiger shark hung, and the Kelley House and Harbor View hotels, where many of the cast members stayed. The Amity National Bank sign that Universal used during the filming of "Jaws" is now hanging inside the Rockland Trust Bank in Edgartown. Pamela Wright Heading out of town, we drove past State Beach, and near where Chrissy and Pipit the dog met their demise. And finally, to the infamous Jaws Bridge (a.k.a. American Legion Memorial Bridge). 'This is where I died,' said Voorhees. 'Right there at the end of the jetty.' There's a No Jumping sign posted on the bridge, but we watched two young boys leap off it. 'Everyone does it,' Voorhees said. Unless there's a shark in the water, dun-dun, dun-dun… Diane Bair and Pamela Wright can be reached at
