Two significant research developments, presented in the US last week, are being hailed as major breakthroughs in the search for cures for multiple myeloma and breast cancer, notes MedicalBrief. Positive results after a study of CAR-T treatment on multiple myeloma and a new drug that could stop some breast cancer tumours from using hormones to grow have upped the stakes in cancer research.
Both studies were reported this past weekend at the annual conference of the American Society of Clinical Oncology in Chicago. It comes as scientists worldwide are edging towards more effective cancer treatments, and possibly cures for some cancers (see story in SideBar).
In the first study, the group of 97 patients had longstanding multiple myeloma, a common blood cancer considered by doctors to be incurable. All faced a certain, and extremely painful, death within about a year.
They had undergone 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.
And so they all got immunotherapy, in a study that was seen as a last resort. But a third of patients in the Johnson & Johnson clinical trial have lived without detectable cancer for years after facing certain death.
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.
The New York Times reports that these results, in patients whose situation had seemed hopeless, has led some battle-worn American oncologists to dare to say the words “potential cure”.
“In my three decades in oncology, we haven’t talked about curing myeloma,” said Dr Norman Sharpless, a former director of the National Cancer Institute and 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.”
Drastic illness
The study, which was published in The Journal of Clinical Oncology, was funded by Johnson & Johnson, which has an exclusive licensing agreement with Legend Biotech.
Patients who develop multiple myeloma each year face an illness that eats away at bones, so it looks as though holes have been punched out in them, said Dr Carl June, of the University of Pennsylvania. June has seen patients who lost 15cm in height.
“It’s a horrible, horrible death,” he said. “Right now, advanced myeloma is a death sentence.”
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 – or CAR-T – 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 revolutionised prospects for patients with other types of blood cancer, like leukaemia.
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 hospitalised for weeks after receiving it.
But Legend managed to develop one that works in multiple myeloma, defying sceptics.
The Chinese company gained attention for its CAR-T eight years ago when it made extravagant claims, which were met by sniggers from American researchers.
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.
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.
Challenge
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 lifespan 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.
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, “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 importantly, 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”.
Breast cancer breakthrough
On the other side of the world, a trial has raised hopes that a new drug could stop some breast cancer tumours from using hormones to grow, after reducing patient’s chances of the disease progressing by 52% compared with standard therapies.
Cancer Research UK said the Serena-6 trial findings suggest that using camizestrant could help patients stay well longer and delay the need for chemotherapy.
The drug works by blocking oestrogen from getting into the breast cancer cell, which the scientists hope can then stop or slow the growth of cancer, reports Sky News.
The trial was carried out with the Institute of Cancer Research (ICR) in London.
“The results represent more than a clinical milestone; they represent a transformational shift in how we approach precision medicine,” said Professor Kristian Helin, ICR chief executive.
Co-principal investigator Professor Nick Turner also called the development of the drug “a pivotal moment in breast cancer care”.
The study, funded by AstraZeneca, looked at patients with hormone-positive, HER2-negative breast cancer – about 70% of cases.
More than 3 000 patients from 23 countries took part in phase three of the trial, which saw doctors use blood tests to detect changes in the cancer’s DNA to see which treatments were ineffective.
For those taking camizestrant, their cancer stabilised for around 16 months on average, compared with about nine months for other treatments.
However, 1% of patients taking the new drug stopped taking it because of side effects.
Further results were published in New England Journal of Medicine.
First worldwide
The trial was also the first worldwide study to show that using blood tests to find early signs of cancer resistance to treatment helps patients.
Dr Catherine Elliott, director of research at Cancer Research UK, said the breakthrough was a clear example of how blood tests are starting to transform cancer treatment.
“By tracking tiny traces of tumour DNA in the blood, researchers were able to spot early signs of treatment resistance and switch therapies before cancer had a chance to grow,” she added.
“It shows how circulating tumour DNA, or ctDNA, could help doctors make smarter, more timely treatment decisions This approach could become an important part of how we personalise care for people with advanced breast cancer.”
See more from MedicalBrief archives:
FDA flags J&J, Bristol’s CAR-T therapies
FDA probes safety of CAR-T therapies
Best contender in decades in breast cancer fight – global study
AstraZeneca and partners launch initiative for cancer patients across Africa
ESMO 2021: Highly promising results against breast and ovarian cancer