CAR T a ‘Bridge’ to Stem Cell Transplant for Some Tough Cases

June 21, 2019 | by Abe Rosenberg

You could call it a match made in scientific heaven.
Two breakthrough technologies — stem cell transplants and CAR T cell therapy — can work together to help more leukemia patients than ever before, including many who have exhausted all other options.
Since beginning its transplant program in 1976, City of Hope has performed over 15,000 bone marrow and stem cell transplants, achieving progressively higher survival rates. Transplants — replacing the patient's diseased cells with healthy ones from a carefully matched donor — remain the only realistic path to a cure for leukemia and other blood diseases.
For a transplant to have a better-than-even chance of success, it's necessary to push the patient's disease into remission first. Doctors typically administer a variety of first-line or “induction” chemotherapy drugs to bring about the remission, paving the way for the transplant to take place.
Unfortunately, chemo doesn't work for every patient. Worse, if the first drug doesn't do the job, second-and-third-line drugs (also called “salvage” chemo) are even less likely to trigger long-lasting remission because the disease develops drug resistance.

CAR T Before Transplant

For those patients, CAR T cells may be the best answer.
CAR T cell treatment is a leading-edge immunotherapy system that reengineers a patient's own immune cells to target and attack cancer. It's being tested on everything from prostate cancer to brain tumors, and the Food and Drug Administration has approved two CAR T formulations for treating leukemia and lymphoma.
“CAR T cell therapy may allow patients who otherwise couldn't have transplants — like those with active leukemia — to undergo the procedure successfully,” said Samer Khaled, M.D., associate clinical professor in the Department of Hematology & Hematopoietic Cell Transplantation.
Khaled and his colleagues believe CAR T cells may accomplish what chemo cannot: Create durable remissions in even the toughest leukemia cases, making it an effective “bridge” to transplants.
“With CAR T cells we get deeper remissions, with most if not all the cancer cells eradicated,” said Khaled. “With chemo, the remissions are not as deep.” What's more, the CAR T effect is ongoing, because those reintroduced, specially engineered immune cells continue to kill cancer cells over a longer period of time.
Creating that “deep” remission, then following up with a transplant, turns out to be a powerful combination. A growing body of data is backing that up, and in Khaled's own study of patients who did both CAR T and a transplant, only one has relapsed.

CAR T in Lieu of Transplant?

Indeed, CAR T cell treatments work so well, it's fair to ask: Will the day come when CAR T alone will be enough, and transplants won't be necessary? It's certainly possible, Khaled says. For now, however, we don't have enough data to accurately predict which CAR T cell patients will relapse and which will not. “That's the big question,” he said. “Who needs only CAR T cells by themselves, and who should receive CAR T therapy followed by a transplant?” Answers will come, he said, as we learn more about the persistence of the CAR T cells' effect.
What we know right now is that only a certain kind of patient can withstand the double rigors of both a CAR T regimen and a stem cell transplant. Each procedure can be grueling and carries its own risks: CAR T cell treatment may lead to cytokine-release syndrome, a sometimes life-threatening complication. Transplants run the risk of graft-versus-host disease, when the implanted cells react to the patient’s body.
“A patient who's already seriously sick couldn't tolerate all that,” Khaled said, pointing out that it takes time and considerable stamina to go through CAR T cell therapy, recover from it, then move on to the stem cell transplant and recover from that as well. “The ideal patient would be someone who's relatively fit, hasn't had a prior transplant, was given chemo unsuccessfully, and is now awaiting a transplant from a well-matched donor.”
Perhaps it's only natural, even inevitable, that City of Hope take the lead in employing CAR T cell therapy and stem cell transplants together. City of Hope is home to one of the most comprehensive CAR T cell programs in the world, with 16 clinical trials underway and more to come. Having that expertise on the same campus together with one of the country's premier stem cell transplant teams brings about the kind of breakthrough collaborations difficult to achieve elsewhere.
Collaborations that lead to lifesaving results.
“The most important thing to remember,” Khaled said, “is that this new therapy brings new hope to patients whose disease wasn't controllable, to allow them to proceed to a stem cell transplant for a potential cure.”

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