The Next Challenge for CAR T: Reaching More Patients
- CAR T-cell therapy can produce long-lasting remissions for some people with blood cancer, but many patients still struggle to access it because of its complex manufacturing process and the need for specialized treatment centers.
- In an interview with SurvivorNet, Allogene Therapeutics CEO Zach Roberts outlines his efforts to remove some of those barriers with an “off-the-shelf” CAR T approach that uses healthy donor cells prepared in advance, potentially making treatment faster and easier to deliver.
- Allogene is testing whether its approach can expand CAR T to get the treatment to patients sooner and in more places, including community oncology practices and earlier treatment for patients with lymphoma who have minimal residual disease.
- The company is also seeing encouraging progress in its CAR T programs, including early results in lymphoma and kidney cancer and FDA designations for cema-cel, an investigational CAR T therapy for certain people with aggressive large B-cell lymphoma.
“If we can’t get these therapies to patients everywhere, then have we really succeeded?” Roberts asks.
Read More“It boils down to conviction and belief in what you’re seeing,” Roberts says. “For me as an oncologist, I have been really quite fixated, obsessed, enamored… with CAR T since the very first publications.”
Allogene is one of the companies developing an allogeneic, or “off-the-shelf,” form of CAR T that uses T cells from healthy donors instead of the patient’s own cells. The cells can be prepared and stored in advance, potentially making treatment available more quickly.
It’s an approach Roberts has pursued throughout much of his career. Now, promising results are giving that strategy new weight, reinforcing the dedication to CAR T that Roberts says “gets me out of bed in the morning.”
CAR T’s Promise — and Its Access Problem
Since the first CAR T therapies were approved in 2017, the treatment has transformed outcomes for some patients with non-Hodgkin lymphoma and multiple myeloma. But only a fraction of eligible patients receive it.
“In fact, only about 15% of patients with lymphoma whose lymphoma recurs or relapses after first-line therapy are ever even receiving these therapies,” Roberts says.
“Have we really solved this problem if 85% of the patients who could benefit are not being offered these therapies?” he asks.
A CAR T-Cell Access Crisis
The answer depends on changing how CAR T is made.
Roberts says the limited availability of current CAR T therapies is “a stain on the legacy of CAR T.”
“So what Allogene is looking to do is first — we have changed the way we manufacture these products,” he says.
Ready When Patients Need It
Allogene’s approach allows treatment to be manufactured and stored in advance, so it is ready when a patient needs it.
“We make all these products well in advance. We put them in a freezer and we ship them out as soon as the patient needs them.”
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Allogene is also testing whether its approach can move CAR T beyond major academic and transplant centers and into community oncology practices.
Early results from the company’s ALPHA3 trial offer some encouragement. The study is testing CAR T shortly after first-line treatment in patients with minimal residual disease (MRD), or tiny amounts of cancer that remain after treatment.
Early results showed:
- 58% of patients had detectable MRD eliminated
- 0 cases of cytokine release syndrome (CRS)
- 0 cases of neurotoxicity
Most patients received treatment in an outpatient setting, including at community centers or through their regular oncologists, Roberts says.
“This toxicity profile really puts that efficacy signal in great context and is the thing that actually allows us to envision getting into community practices broadly.”
The findings remain early, but they point to a potential path for bringing CAR T closer to where more patients receive cancer care.
Could Earlier Treatment Prevent Relapse?
Allogene is also studying whether CAR T could be used earlier, before cancer returns.
The company’s ALPHA3 trial is testing CAR T in patients with MRD after first-line treatment, with the goal of eliminating residual cancer before it develops into a full relapse.
“Is it really the right thing to wait for patients’ disease to come back before we treat them?” Roberts asks.
The strategy is based on the idea that CAR T may work better when there is less cancer in the body.
“When you’re treating patients who only have what we call molecularly detectable disease… those patients have the smallest amount of disease that you can measure,” Roberts says. “And so administering a new treatment in that moment likely will bring strong efficacy and better safety.”
But using CAR T earlier would make the access challenge even more important.
‘New and Exciting Data’ in Kidney Cancer
Allogene is also testing whether its off-the-shelf CAR T platform can work beyond blood cancers.
On July 14, Allogene published data from its CAR T solid-tumor program in metastatic kidney cancer. Among patients with high CD70 expression, 31% achieved deep, durable remissions lasting up to 18 months after a single CAR T dose. The median response duration had not yet been reached.
CAR T in Metastatic Kidney Cancer
- 31% responded among patients with high CD70 expression
- 18 months was the longest observed response
- 1 dose of allogeneic CAR T
Allogene reported the first durable remissions from allogeneic CAR T in metastatic solid tumors.
“Really new and exciting data there,” Roberts says.
The results are early, and solid tumors remain a major challenge for CAR T, but they provide another test of whether an off-the-shelf approach can expand the reach of cell therapy.
A Physician-Scientist at Heart
Roberts was part of the team that developed Yescarta, one of the first CAR T therapies approved for certain patients with non-Hodgkin lymphoma. That experience shaped his belief in both CAR T’s potential and the need to make it more accessible.
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Now, he is leading a company trying to solve one of the therapy’s biggest challenges: manufacturing and delivering it at scale.
For Roberts, that question may be just as important as whether CAR T works.
“Even though I am the CEO of Allogene now, at my heart I’m a physician-scientist, and I’ll always be a physician-scientist,” he says. “That is what gets me out of bed in the morning.”
The science behind CAR T may be revolutionary. The next challenge is making sure patients can actually get it.
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