Inside Precision Medicine
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A phase I clinical trial at Stanford Medicine has found that a new CAR-T cell therapy that targets a different protein—CD22—from the original therapy significantly improved patients’ outcomes. Over half of 38 people enrolled in the trial—37 of whom had already relapsed from the original CAR-T therapy—experienced a complete response by their cancers. More than half of all treated patients lived at least two years after treatment.
“On average, the patients enrolled in this trial had received four previous lines of therapy,” said assistant professor of medicine Matthew Frank, MD, PhD, a lead author of the paper. “These patients are out of likely curative options, and they are scared. Half of them will die within five to six months. But in this trial, we saw a very high rate of durable complete responses, meaning their cancers became undetectable.”
The study was published July 9 in The Lancet. The senior author is David Miklos, MD, PhD, professor of medicine and chief of bone marrow transplantation and cellular therapy at Stanford.
CAR-T cell therapy targets a specific protein on the surface of cancer cells causing tumors to shrink or disappear in about half of patients with large B-cell lymphoma, but if the treatment fails, or the cancer returns yet again—as happens in approximately half of people—the prognosis is dire. The median survival time after relapse is about six months.
CD22 is a nearly universally expressed B-cell surface antigen. The efficacy of a CD22-directed CAR T-cell therapy was previously little studied in large B-cell lymphoma, but in September 2022, the FDA designated CD22-targeting CAR-T therapy for large B-cell lymphoma a Breakthrough Therapy. A larger, phase II trial of the new therapy, led by Frank, is now ongoing at multiple sites around the country.
CAR-T cell therapy was first approved by the FDA as a treatment for relapsed or treatment-resistant diffuse large B-cell lymphoma and for children and young adults under 25 with acute lymphoblastic leukemia. Six CAR-T cell therapies are now approved for several types of lymphoma, multiple myeloma and acute lymphoblastic leukemia. Four of these therapies target CD19, which is found on the surface of healthy and cancerous B cells; two target another protein on the cells’ surface called B cell maturation agent.
In this Stanford study, the researchers collected immune cells called T cells from 38 patients with large B-cell lymphoma whose cancers had started growing after previous therapies including chemotherapy. All but one of the patients had also progressed after CAR-T therapy targeting CD19; the cancer cells of the one remaining patient did not express CD19 on their surfaces.
The T cells were grown and genetically engineered to target CD22 in Stanford Medicine’s Laboratory for Cell and Gene Medicine in partnership with the Center for Cancer Cell Therapy. They were then infused back into the patients from whom they were derived.
Of the 38 patients, 68% saw their cancers shrink, and 53% achieved a complete response, meaning their cancers were no longer detectable.
“This is not just a high response rate, but many of these remissions have been quite durable over a median of 30 months of follow-up,” Frank said. “If this holds true in larger trials, it will surpass other therapeutic options we have for these patients.” Additionally, most patients experienced minimal, manageable side effects.
News & FeaturesB-cell lymphomaCell therapyMultiple myelomaPhase I clinical trials (Clinical trial)
