NEW YORK – Atlantic Health System is enrolling patients with a severe form of lupus in which they don't respond to standard treatment into an early-stage clinical trial to receive an experimental CAR T-cell therapy.
Investigators at the Morristown, New Jersey-based hospital system are some of the earliest to try using a CAR T-cell therapy, a therapeutic approach which, to date, has primarily been used within oncology, as a treatment for lupus, a chronic autoimmune disease in which the immune system attacks the body's own tissues and organs.
"There's a significant need for more effective treatments in this patient population," said Neil Kramer, a rheumatologist at Atlantic Health System and cofounder of the Institute for Rheumatic and Autoimmune Diseases at the hospital system's Overlook Medical Center.
Kramer is a principal investigator on a Phase I multicenter, open-label clinical trial, sponsored by Bristol Myers Squibb, on the safety and preliminary efficacy of the company's CD19-targeted CAR T-cell therapy for adults with severe, refractory autoimmune diseases. The study launched last year with a focus on systemic lupus erythematosus (SLE), and in March 2024 expanded to include patients with idiopathic inflammatory myopathy and systemic sclerosis.
Atlantic Health System, one of more than 50 clinical trial sites in the US and Europe, treated the first US patient in that Phase I study late last year.
BMS did not respond to a request for comment on its development plans for the cell therapy, which it refers to as CC-97540 and BMS-986353, but in late 2023 said one of its priorities was to build the company's leadership in the cell therapy space, including expanding its clinical development work in immunology.
Lupus has quickly become an entry point for companies interested in testing CAR T-cell therapy in autoimmune indications, with researchers suggesting that such therapies can improve or even relieve patients' symptoms by targeting and depleting B cells, a part of the immune system that's dysfunctional in SLE patients.
Other companies, including Cabaletta Bio, Cartesian Therapeutics, ImmPact Bio, and Novartis Pharmaceuticals, are also clinically testing CAR T-cell therapies in patients with SLE. Earlier this year, researchers in Germany published an analysis that included eight SLE patients who had sustained remission for more than two years after treatment with an autologous CAR T-cell therapy.
In the ongoing BMS Phase I study, investigators extract a patient's own T cells, which are made into CAR T cells that target and deplete B cells. That process takes two to four weeks, after which the cells are then infused back into the patient.
Before treatment, the patient also receives a chemotherapy regimen, which takes three days.
The idea behind the CAR T-cell therapy is that once B cells are removed, the body will replace them with healthy B cells that aren't autoreactive.
"These engineered CAR T cells act like soldiers, seeking out and eliminating B cells in various tissues, aiming to halt the progression of lupus and restore immune balance," said Mohamad Cherry, medical director of hematology/oncology at Atlantic Health System and medical director at the Atlantic Cellular Therapy Program, who's collaborating with Kramer on the clinical trial.
That process holds potential for other autoimmune diseases that are also triggered by overactive B cells that attack the body's healthy tissues.
"If the application of CAR T cells for lupus turns out to be as successful as we anticipate, then we can take other autoimmune diseases, apply the same principle, and hopefully, have the same results," Cherry said.
Standard care for SLE tends to include a combination of multiple medications to control disease symptoms. That can involve the antimalarial drug Plaquenil (hydroxychloroquine), as well as corticosteroids, immunosuppressants, biologics, and other medications.
The ultimate goal for an SLE therapy would be for a patient to reach a state of low disease activity or complete remission of symptoms, Kramer said. So, in studying this therapy, Kramer said he and other colleagues will be looking at key questions such as whether patients reach disease remission, the duration of such remission, and what to do if the disease recurs.
However, there are risks, Kramer noted.
Patients must be weaned off of their other medications, aside from low-dose prednisone, two or three weeks before T cells can be collected, which can result in a disease flare-up. On top of that, the chemotherapy regimen includes drugs that can cause bone marrow suppression or a decrease in bone marrow's ability to produce red and white blood cells.
That means there's a potentially significant risk of infection within those first few months, Kramer said. It's something that investigators are keeping an eye on, with primary outcomes for this study focusing on safety. In fact, patients remain in the hospital for about two weeks after the infusion to monitor for side effects and signs of infection, he added.
"At least for now, and until [the] CAR T therapy is shown to be both safe and effective for SLE, this therapy will be reserved for patients with more severe forms of the disease who have not responded to the current standard of care therapy," Kramer said. "While expectations are high, it's essential to gather more data."