ASH23: CAR-T for autoimmune disease, real-world questions and sickle cell’s social media mentions

ASH23: CAR-T for autoimmune disease, real-world questions and sickle cell’s social media mentions

SAN DIEGO —The 65th annual meeting of the American Society of Hematology got a dramatic introduction. On Friday, as researchers and doctors arrived here, the Food and Drug Administration approved two gene therapies for sickle cell disease, an inherited condition that for several years now has been a regular focus on the conference. 

“ASH 2023 is going to be marked by these two FDA approvals,” said Alexis Leonard, a hematologist and assistant faculty member at St. Jude Children’s Research Hospital. “This is 10 years’ worth of clinical trial work and 30 years of basic science culminating in what happened yesterday.” 

Both Vertex Pharmaceuticals and Bluebird bio, respectively makers of the two therapies, are at ASH with updated data for their treatments, which will soon be available in the U.S. for people with sickle cell aged 12 years or older. For Bluebird, it’s the seventh year running that it has presented sickle cell data here. 

While the approval news may be the biggest headline, there are many other studies of note, including one of CAR-T therapy in autoimmune disease and another highlighting the difference between the trial setting and the real world.

CAR-T’s next use case

Could CAR-T cell therapy’s next application be in treating autoimmune disease? A small academic study in Germany is offering clues. 

An initial slice of data, from the first five study participants, drew attention to the question last year. At ASH on Saturday, researchers led by Fabian Mueller of the Bavarian Cancer Research Institute presented new results from 15 patients with lupus or two other autoimmune diseases.

Their findings suggest CAR-T therapy, currently used for blood cancers like leukemia and lymphoma, could treat those immune conditions, too. 

“All [patients] remain in complete remission since we have treated them with CD19 CAR-T cells,” said Mueller, at an ASH press conference Saturday. “At least for now, it’s a lasting remission.”

In a related statement, he shared how the first lupus patient treated with CAR-T in the trial was so sick at the time that she wasn’t expected to live much longer than a month. Now she’s running five days a week, he said.

The rationale for using CAR-T in autoimmune diseases has to do with how the treatments work. They consist of a patient’s own immune cells, engineered to target a protein called CD19 that’s typically found on the surface of B cell cancers. But it appears these souped-up cells can also destroy misfiring B cells that are responsible for the immune attack that inflammatory diseases like lupus inflict on the body. 

So far, the 15 patients in the study have been followed for a median of 15 months after their CAR-T infusions. All are doing well and have stopped taking immunosuppressive drugs. Two-thirds experienced a mild form of cytokine release syndrome, an immune side effect of CAR-T therapy, but there were no serious treatment-related adverse events.

Mueller and his fellow researchers are hopeful their findings could lead to an alternative treatment to autologous stem cell transplant in people with life-threatening autoimmune diseases.

“Of course we need longer follow-up to establish how effective the treatment is going to be in the long run,” said Mueller. 

There are signs drugmakers are paying attention. A group of biotechnology companies are exploring whether a special type of immune cell called Tregs could be used for autoimmune cell therapies. And earlier this month, CRISPR Therapeutics, in a research pivot, said it was planning to test one of its experimental CAR-T therapies in lupus.

One potential hurdle? An investigation by the FDA into the possible risk of T cell malignancies in people who received CAR-T therapies for cancer. While the agency believes the benefits outweigh the risks, that balance might be different in autoimmune diseases. 


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