Month: July 2025

One Third of Near-Death Multiple Myeloma Patients Are Cured by a New CAR-T Immunotherapy

Many consider immunotherapy to be the most promising current approach to curing cancer. One way to implement immunotherapy is to develop CAR-T cells. But there apparently are many ways to develop a CAR-T cell and which, if any, will work is a matter of trial-and-error.

It seems overly-cautious for regulators to require that the most innovative and promising therapies must first be tried on the patients nearest to death, and so least likely to respond. Why not allow patients at earlier stages to volunteer to try the new therapies earlier? They would be taking a bigger risk, but also would have the possibility of a bigger benefit. They would avoid the suffering from current treatments that are known to have major side-effects, and also are known to only extend life for short periods of time; and they would gain a shot at a real long-term cure.

(p. A18) A group of 97 patients had longstanding multiple myeloma, a common blood cancer that doctors consider incurable, and faced a certain, and extremely painful, death within about a year.

They had gone through a series of treatments, each of which controlled their disease for a while. But then it came back, as it always does. They reached the stage where they had no more options and were facing hospice.

They all got immunotherapy, in a study that was a last-ditch effort.

A third responded so well that they got what seems to be an astonishing reprieve. The immunotherapy developed by Legend Biotech, a company founded in China, seems to have made their cancer disappear. And after five years, it still has not returned in those patients — a result never before seen in this disease.

These results, in patients whose situation had seemed hopeless, has led some battle-worn American oncologists to dare to say the words “potential cure.”

. . .

The new study, reported Tuesday [June 3, 2025] at the annual conference of the American Society of Clinical Oncology and published in The Journal of Clinical Oncology, was funded by Johnson & Johnson, which has an exclusive licensing agreement with Legend Biotech.

. . .

The Legend immunotherapy is a type known as CAR-T. It is delivered as an infusion of the patient’s own white blood cells that have been removed and engineered to attack the cancer. The treatment has revolutionized prospects for patients with other types of blood cancer, like leukemia.

Making CAR-T cells, though, is an art, with so many possible variables that it can be hard to hit on one that works.

. . .

The . . . study took on a . . . challenge — helping patients at the end of the line after years of treatments. Their immune systems were worn down. They were, as oncologists said, “heavily pretreated.” So even though CAR-T is designed to spur their immune systems to fight their cancer, it was not clear their immune systems were up to it.

Oncologists say that even though most patients did not clear their cancer, having a third who did was remarkable.

To see what the expected life span would be for these patients without the immunotherapy, Johnson & Johnson looked at data from patients in a registry who were like the ones in its study — they had failed every treatment. They lived about a year.

. . .

. . ., the hope is that perhaps by giving it earlier in the course of the disease, it could cure patients early on.

Johnson & Johnson is now testing that idea.

Dr. Kenneth Anderson, a myeloma expert at Dana-Farber Cancer Institute who was not involved with the study, said that if the treatment is used as a first-line treatment, “cure is now our realistic expectation.”

For the full story, see:

Gina Kolata. “From No Hope to Potential Cure for Deadly Blood Cancer, Study Shows.” The New York Times (Thurs., June 5, 2025): A18.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the story was updated June 5, 2025, and has the title “From No Hope to a Potential Cure for a Deadly Blood Cancer.”)

The academic article on the new cure is:

Jagannath, Sundar, Thomas G. Martin, Yi Lin, Adam D. Cohen, Noopur Raje, Myo Htut, Abhinav Deol, Mounzer Agha, Jesus G. Berdeja, Alexander M. Lesokhin, Jessica J. Liegel, Adriana Rossi, Alex Lieberman-Cribbin, Saad Z. Usmani, Binod Dhakal, Samir Parekh, Hui Li, Feng Wang, Rocio Montes de Oca, Vicki Plaks, Huabin Sun, Arnob Banerjee, Jordan M. Schecter, Nikoletta Lendvai, Deepu Madduri, Tamar Lengil, Jieqing Zhu, Mythili Koneru, Muhammad Akram, Nitin Patel, Octavio Costa Filho, Andrzej J. Jakubowiak, and Peter M. Voorhees. “Long-Term (≥5-Year) Remission and Survival after Treatment with Ciltacabtagene Autoleucel in Cartitude-1 Patients with Relapsed/Refractory Multiple Myeloma.” Journal of Clinical Oncology https://doi.org/10.1200/JCO-25-0076.

Public Should Beware of F.D.A.’s Lax Inspections of Drugs Made in India and China

On drug safety, the public puts its trust in the F.D.A. which frequently drops the ball. The public would be better off adopting caveat emptor, and seeking private means of assurance of safety. These would include certification (stamps of approval) from private organizations like the United States Pharmacopeial Convention (USP).

They might also choose to buy well-known name brands, since a well-known brand has more reputation capital to lose if they produce a bad batch, and thus can be expected to invest more in quality control. (Lester Telser made this argument–I need to seek where.)

(p. A10) A highly drug-resistant bacteria that was linked to eyedrops imported from India and that spread from person to person in a Connecticut long-term care center has prompted concerns that the strain could gain a foothold in U.S. health care settings, according to the Centers for Disease Control and Prevention.

. . .

The outbreak has renewed longstanding concerns about the quality and frequency of the F.D.A.’s overseas inspections.

In June 2020, Senator Chuck Grassley, Republican of Iowa, held an oversight hearing on the F.D.A.’s foreign inspection process, noting that the plants were given 12 weeks’ advance notice, “plenty of time to doctor up a facility to make sure that it passes inspection.” The agency has since received budget authority to conduct unannounced overseas inspections.

. . .

The F.D.A. paused overseas inspections during the height of the coronavirus pandemic, and the number of foreign inspections remained low last year, at 684 compared with 3,272 in 2019, according to agency data.

The F.D.A. has 4,000 overseas facilities to inspect, with about 20 percent in India; one of its six inspector positions in that country was vacant in late 2021, according to a report issued last year by the Government Accountability Office.

For over-the-counter drugs, the F.D.A. uses a system that essentially lists a medication recipe. Companies can make the products without express agency approval but are expected to follow agency rules for manufacturing quality products, said John Serio, a lawyer with Withers who has pharmaceutical clients.

“If you’re not out there inspecting facilities,” Mr. Serio said, “these sorts of problems will crop up because there’s no threat that if you’re out of compliance that the inspector will come knocking at your door.”

For the full story see:

Christina Jewett and Andrew Jacobs. “Drug-Resistant Bacteria Linked To Eyedrops Can Easily Spread.” The New York Times (Mon., April 3, 2023 [sic]): A10.

(Note: ellipses added.)

(Note: the online version of the story has the same date as the print version, and has the title “Drug-Resistant Bacteria Tied to Eyedrops Can Spread Person to Person.”)

The F.D.A.’s lax inspections of generic drugs made in India is documented in:

Eban, Katherine. Bottle of Lies: The Inside Story of the Generic Drug Boom. New York: Ecco, 2019.

Electricity May Be a Pellet in the “Magic Buckshot” Against Cancer

In a recent entry I claimed that the cure for many diseases may not be Paul Ehrlich’s one “magic bullet” but may instead be “magic buckshot.” A recent article in The Wall Street Journal suggests that one pellet in the magic buckshot against cancer is electricity. As proof of concept, the article claims that after surgery, radiation, and chemotherapy for a glioblastoma brain cancer, adding electrodes to the skull that deliver low-intensity electricity to the brain, will add a median of 4.9 months to the patient’s lifespan.

The Wall Street Journal article mentioned above is:

Brianna Abbott. “Next Hope in Treating Cancer: Electricity.” The Wall Street Journal (Tues., May 20, 2025): A10.

(Note: the online version of the article has the date May 16, 2025, and has the title “The Next Frontier to Treat Cancer: Electricity.”)

The Wall Street Journal article links to the following article in JAMA:

Stupp, Roger, Sophie Taillibert, Andrew Kanner, William Read, David M. Steinberg, Benoit Lhermitte, Steven Toms, Ahmed Idbaih, Manmeet S. Ahluwalia, Karen Fink, Francesco Di Meco, Frank Lieberman, Jay-Jiguang Zhu, Giuseppe Stragliotto, David D. Tran, Steven Brem, Andreas F. Hottinger, Eilon D. Kirson, Gitit Lavy-Shahaf, Uri Weinberg, Chae-Yong Kim, Sun-Ha Paek, Garth Nicholas, Jordi Bruna, Hal Hirte, Michael Weller, Yoram Palti, Monika E. Hegi, and Zvi Ram. “Effect of Tumor-Treating Fields Plus Maintenance Temozolomide Vs Maintenance Temozolomide Alone on Survival in Patients with Glioblastoma: A Randomized Clinical Trial.” JAMA 318, no. 23 (Dec. 19, 2017): 2306-16.

During Covid-19 “Bureaucratic Authorities Erred in Pretending . . . Certainty”

(p. A13) Adam Kucharski, a professor of epidemiology at the London School of Hygiene & Tropical Medicine, takes the reader on a fascinating tour of the history of what has counted as proof.

. . .

What should we do, . . ., when a mathematical proof of truth is unavailable, but we must nonetheless act?

This leads us to a discussion of probability and statistics, and of pioneers such as William Gosset, a brewer at Guinness who figured out how to quantify random errors in experiments, and Janet Lane-Claypon, an English scientist who first thought to investigate confounding factors while analyzing children’s health. Some innovations, though, have hardened into unhelpful dogma. The scientific notion of “statistical significance” relies, Mr. Kucharski explains, on a wholly arbitrary cutoff, which incentivizes researchers to massage their data. Such issues, he says, can be hard for scientists, let alone the laity, to understand.

Mr. Kucharski speaks from experience, since he was one of the experts first called upon by the British government for advice on the Covid-19 pandemic. He explains brilliantly the fragmentary and confusing nature of the data then available, and the provisional conclusions they led to. As a public face of this effort, Mr. Kucharski was bombarded daily with abusive and threatening messages from angry citizens who simply didn’t believe what they were being told.

The lesson Mr. Kucharski draws isn’t that he and his colleagues were right (though they largely were), but that bureaucratic authorities erred in pretending there was certainty when all that was possible at the time was messy and provisional. Notoriously, in March 2020 the World Health Organization tweeted “FACT: #COVID19 is NOT airbone.” (As it turns out, it was, and it is.) The author regrets, too, that politicians claimed to be “following the science,” because science can never tell you what you should do.

For the full review see:

Steven Poole. “Bookshelf; Finding Truth In Numbers.” The Wall Street Journal (Friday, June 6, 2025): A13.

(Note: ellipses added.)

(Note: the online version of the review has the date June 5, 2025, and has the title “Bookshelf; ‘Proof’: Finding Truth in Numbers.”)

The book under review is:

Kucharski, Adam. Proof: The Art and Science of Certainty. New York: Basic Books, 2025.

Dream of the Magic Buckshot

Paul Ehrlich in the early 1900s sought a “magic bullet” for each disease (including cancer). Given the alternatives at the time, when he found Salvarsan it could be considered a magic bullet against syphilis. Today Dr. Dale Bredesen has replaced “magic” with “silver” and “bullet” with “buckshot.” In his effort to cure Alzheimer’s “Bredesen believed in firing a “silver buckshot” (a reference to the sprayed pellets that come out of shotgun shells) by modifying 36 factors simultaneously” (Gellman, p. 18).

I have not investigated Dr. Bredesen’s “cure” for Alzheimer’s and express no opinion on it. I will express the opinion that I do not like the arrogantly dismissive tone of Lindsay Gellman’sThe New York Times article, bowing to “experts,” but calling Bredesen “Mr.” instead of the “Dr.” he has earned.

And I do like the idea that sometimes what is effective against a disease (including cancer) is not a single drug or therapy, but several taken together. For example, multi-drug cocktails have been effectively used against HIV, childhood leukemia, and Hodgkin’s lymphoma.

Ehrlich’s big dream was to find a magic bullet for each disease. But maybe it is mostly more promising to dream of the magic buckshot.

[N.B., the “Paul Ehrlich” I refer to is not the contemporary environmental alarmist “Paul Ehrlich” who famously lost his bet with the heroic heretic Julian Simon.]

The NYT article quoted above:

Lindsay Gellman. “Lifestyle to Reverse Alzheimer’s Carries High Costs and, Many Say, False Hope.” The New York Times, First Section (Sun., May 25, 2025): 1 & 18.

(Note: the online version of the NYT article was updated May 31, 2025, and has the title “An Expensive Alzheimer’s Lifestyle Plan Offers False Hope, Experts Say.”)