From no hope to a potential cure for a deadly blood cancer

Boston Globe

2 days ago

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.
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These results, in patients whose situation had seemed hopeless, has led some battle-worn American oncologists to dare to say the words 'potential cure.'
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'In my 30 years in oncology, we haven't talked about curing myeloma,' said Dr. Norman Sharpless, a former director of the National Cancer Institute who is now a professor of cancer policy and innovation at the University of North Carolina School of Medicine. 'This is the first time we are really talking seriously about cure in one of the worst malignancies imaginable.'
The new study, reported Tuesday 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 36,000 Americans who develop multiple myeloma each year face an illness that eats away at bones, so it looks as if holes have been punched out in them, said Dr. Carl June, of the University of Pennsylvania. Bones collapse. June has seen patients who lost 6 inches in height.
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'It's a horrible, horrible death,' June said. 'Right now advanced myeloma is a death sentence.' (June has immunotherapy patents that are owned by his university.)
There have been treatment advances that increased median survival from two years to 10 over the past two decades. But no cures.
Dr. Peter Voorhees of the Atrium Health Levine Cancer Institute in North Carolina and the Wake Forest University School of Medicine, who is lead researcher for the newly published study, said patients usually go through treatment after treatment until, ultimately, the cancer prevails, developing resistance to every class of drug.
They end up with nothing left to try.
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. And it can have severe side effects including a high fever, trouble breathing and infections. Patients can be hospitalized for weeks after receiving it.
But Legend managed to develop one that works in multiple myeloma, defying skeptics.
The Chinese company gained attention for its CAR-T eight years ago when it made extravagant claims, which were met by snickers from American researchers.
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Johnson & Johnson, though, was looking for a CAR-T to call its own. So, said Mark Wildgust, an executive in the oncology section of the American drug giant, the company sent scientists and physicians to China to see if the claims were true.
'We went site by site to look at the results,' he said.
The company was convinced. It initiated a collaboration with Legend and began testing the treatment in patients whose myeloma had overcome at least one standard treatment. Compared with patients who had standard treatment, those who had the immunotherapy lived longer without their disease progressing.
The immunotherapy received regulatory approval in that limited setting and is sold under the brand name Carvykti. The study did not determine whether this difficult treatment saved lives.
The new study took on a different 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.
For Anne Stovell of New York, one of the study patients whose cancer disappeared, the result is almost too good to be true.
She says she went through nine drugs to control her cancer after it was diagnosed in 2010, some of which had horrendous side effects. Each eventually failed.
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Taking the Legend CAR-T was difficult -- she said she had spent nearly three weeks in the hospital. But since that treatment six years ago, she has no sign of cancer. She said it was still difficult for her to believe her myeloma is gone. A new ache -- or an old one -- can bring on the fear.
'There's that little seed of doubt,' she said.
But in test after test, the cancer has not reappeared.
'It's a relief for me every year to get a bone marrow biopsy,' she said.
Myeloma experts applauded the results.
Like treatments for many other cancers, treatments for multiple myeloma come with a high price.
The drugs are 'hideously expensive,' June said, costing more than $100,000 a year.
The total cost over the years can be millions of dollars, June said, usually paid by insurers, 'and it doesn't even cure you.'
CAR-T is expensive too. Carvykti's list price is $555,310. But it is a one-time treatment. And, more important, 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.'
That, at least, is the hope, Sharpless said.
And for those like the patients in the new study who are living at least five years -- so far -- without disease, the outcome 'really is eye-popping,' Sharpless said.
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'That's getting to a point where you wonder if it will ever come back,' he added.
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