CAR T-cell therapy may be effective for hard-to-treat LEMS: Case study
Anti-CD19 cell therapy worked for man not responding to other treatments
Anti-CD19 CAR T-cell therapy was found to be effective in treating a 54-year-old man with Lambert-Eaton myasthenic syndrome (LEMS) who wasn’t responding to other immune-suppressing and symptomatic treatments, according to a case report from researchers in Germany.
The team’s observations suggest that this type of cell therapy may be an effective option for hard-to-manage LEMS.
“In severe cases, current immunosuppressive and immunomodulatory treatment strategies are often insufficient,” the researchers wrote. “We here present a case of idiopathic [without any known cause] LEMS … [in which the patient] significantly improved upon treatment with anti-CD19 CAR-T cells.”
The case was detailed in “Anti-CD19 CAR-T cells are effective in severe idiopathic Lambert-Eaton myasthenic syndrome,” a study published in Cell Reports Medicine.
Man’s walking ability improved eightfold after CAR T-cell therapy
LEMS is an autoimmune disease in which the immune system makes antibodies that target voltage-gated calcium channels, or VGCCs — proteins on nerve cells that play a key role in nerve-muscle communication. When antibodies attack VGCCs, nerves aren’t able to correctly send signals instructing muscle cells to contract, ultimately leading to LEMS symptoms.
Treatment of LEMS often involves immune-suppressing or immunomodulatory therapies that aim to dampen the disease’s driving autoimmune attack.
CAR T-cell therapy is a type of immunotherapy that involves collecting T-cells, a type of immune cells, from a patient, then engineering those cells in a lab to equip them with a chimeric antigen receptor, or CAR. A CAR is a man-made protein that directs T-cells to attack a specific molecular target. The modified cells are then infused back into the patient.
Some of the first CAR T-cells specifically used a CAR that targets CD19, a protein found on B-cells — the immune cells responsible for making antibodies, including the anti-VGCC antibodies that drive LEMS. Anti-CD19 CAR T-cells were originally developed as a treatment for blood cancers in which B-cells grow out of control. However, in recent years they have been increasingly studied as a potential therapy for antibody-driven autoimmune diseases such as LEMS.
Here, the researchers describe the case of a man in his 50s who had LEMS that was causing severe symptoms. The man had difficulty raising his limbs and could walk only about 11 meters (approximately 36 feet) with the aid of a walker. He also needed help with daily activities, such as rolling over in bed and shaving.
A range of immune-suppressing and immunomodulatory treatments had been used in an attempt to ease the patient’s symptoms. These included corticosteroids, rituximab, and plasma exchange therapy. While these treatments were effective for managing other co-occurring autoimmune diseases that the man was dealing with, his LEMS remained difficult to treat. The approved symptomatic LEMS therapy Firdapse (amifampridine) also failed to substantially ease his symptoms.
Clinicians eventually decided to try anti-CD19 CAR T-cell therapy. T-cells were successfully collected from the patient and engineered to be equipped with a CAR targeting CD19 before being infused back into the patient. The patient also received a regimen of chemotherapy treatments to deplete his existing immune cells and make room for the engineered T-cells.
A significant improvement of LEMS symptoms [was seen] within the three months following CAR-T cell infusion.
In the first weeks after CAR T-cell therapy, the man developed cytokine release syndrome — an inflammatory condition that’s a known side effect of this type of therapy. This caused fever and general sickness, and his LEMS symptoms appeared to worsen.
This side effect eventually resolved, however, and the man was discharged from the hospital about two weeks after CAR T-cell treatment.
From there, his condition gradually improved. In fact, within about a month of treatment, he was able to roll over in bed by himself, and soon after, was also able to shave independently. He also had an easier time moving his limbs, according to the researchers. While he still needed a walker to get around, the distance he could walk at one time increased to 90 meters, or nearly 300 feet.
“In this patient, CAR-T [cell] infusion … [resulted] in a clinical improvement [or easing] of LEMS symptoms, [with an] 8-fold increase in walking distance,” the researchers wrote, noting “a significant improvement of LEMS symptoms within the three months following CAR-T cell infusion.”
Overall, anti-CD19 CAR T-cell therapy showed good efficacy and an acceptable safety profile in this patient. Given these results, the researchers said that further studies of this type of treatment are warranted in LEMS.
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