5 lupus patients in remission following CAR T cell therapy

Published: Sep 16, 2022

By Tristan Manalac

BioSpace

Five patients with systemic lupus erythematosus (SLE) are in remission after receiving CAR T cell therapy, according to a study published Thursday in Nature Medicine.

The paper shows that all five patients remained in remission for an average of eight months after CAR T treatment—without the need for other drugs to keep the disease at bay. During this time, lupus was nearly undetectable, with patients having a median SLE Disease Activity Index score of 0. 

Still, the researchers are careful to point out that it is too early to know how long CAR T cells can keep SLE patients in remission or if this approach promises a permanent cure. “Sustained drug-free remission of SLE needs to be confirmed over time,” they wrote.

In the study, T cells were drawn from the patients themselves and transduced with a lentiviral anti-CD19 CAR vector. The cells were allowed to multiply before they were re-infused into the patients. They had received a short course of chemotherapy with fludarabine and cyclophosphamide to deplete their bodies’ T cell population. 

The study sample included four women and one man, ranging from 18 to 24 years old. All had received refractory to many lines of prior treatment and used CAR T treatment as part of a compassionate-use program.

After infusion, CAR T cells expanded robustly inside the patients, leading to notable improvements in SLE’s clinical and laboratory measures, including the seroconversion of anti-double-stranded DNA antibodies. 

There were no signs of SLE relapse, even in the first patient to receive the treatment, which was followed for 17 months. 

The researchers attributed this durability of response to what they called the “deep depletion” of B cells.

While the initial CAR T cell infusion strongly suppressed B cell levels in all five patients, this effect started waning after about three months. However, even after B cells returned, patients stayed in remission with almost negligible disease activity, clinical manifestations and biochemical markers. Immunosuppressive medicines also remained unnecessary.

The new batch of B cells also showed markers of being naïve and displayed no signs of humoral autoimmunity, suggesting that the CAR T treatment had “rebooted” the immune system, the researchers noted.

Regarding safety, cytokine release syndrome was at most mild in the study participants, despite common toxicity associated with CAR T therapies in cancer. Three patients came down with fevers, while four had heightened levels of blood inflammatory markers. 

There were no episodes of immune effector cell-associated neurotoxicity syndrome, another typical side effect of CAR T treatments in cancer. 

Nevertheless, the researchers wrote that a CAR T approach to autoimmune disorders is risky, cautioning that the infusion of CAR T cells in these patients could trigger a systemic inflammatory response. 

While the current study painted an excellent tolerability profile for CAR T in SLE, future studies with longer follow-ups and larger samples are vital to validate its safety and curative potential in this disease.

Source: BioSpace