A 24-year-old woman with refractory lupus nephritis has achieved two successful pregnancies following dual-target CAR-T cell therapy, with no evidence of CAR-T cell transmission to either infant, Chinese researchers report.
Writing in Arthritis & Rheumatology [link here], the team from Zhongshan People’s Hospital said the case demonstrated that the emerging therapy could induce long-term systemic lupus erythematosus remission, while preserving fertility, resulting in the delivery of healthy neonates.
The patient was diagnosed with SLE at age 20 and developed class IV lupus nephritis, receiving initial treatment with immunosuppression. Following relapse, she enrolled in a phase 1 trial of BCMA/CD19 directed CAR–T cell therapy.
After achieving sustained molecular remission, the patient became pregnant spontaneously at 6-months and 21-months post infusion, the researchers said.
Throughout both pregnancies, data revealed the patient’s lupus activity remained minimal without flares or any new disease activity. Testing of relevant blood markers also showed sustained immunosuppression of autoimmune activity.
While some proinflammatory cytokines and inflammation-related cellular markers were elevated late in the second pregnancy, there appeared to be no resulting adverse effects.
Both vaginal deliveries of healthy neonates were uncomplicated and to term.
While the patient had low levels of CAR–T DNA detected by quantitative PCR in her peripheral blood at seven months post-infusion – which was gestational week four, later analysis of the patient’s blood, breast milk, and placenta, as well as the infants’ blood at birth and during follow-up, were all negative for CAR–T cell DNA.
Immunophenotyping of maternal peripheral blood late in the pregnancy and of neonatal blood at 48 hours and one year backed up the absence of CAR–T cell transmission and demonstrated robust immune development in the offspring.
Both infants showed normal growth, neurodevelopment, and immune function.
“Collectively, these results indicate that maternal CAR–T cell infusion does not compromise neonatal immune development nor does it engender autoimmune or infectious sequelae,” the researchers said in their brief report.
“Remarkably, [the patient] experienced two spontaneous term pregnancies without relapse, suggesting that the immune ‘reset’ conferred by CAR–T cells remained stable even under the physiologic stresses of pregnancy.”
Interestingly, the researchers said CAR–T cell therapy might even mitigate the typical obstetric complications of SLE such as placental inflammation, preeclampsia, and neonatal lupus, through its effect on immune quiescence.
The researchers noted that in oncology studies, CAR–T cell DNA had been detected in breast milk for years after infusion, but not in cord blood or infant peripheral blood, leading to some clinicians discouraging breastfeeding.
They said these latest findings highlighted the “urgent need” for expanded research, evidence-based fertility guidelines for patients considering pregnancy after CAR–T cell therapy and further evaluation of the safety of breastfeeding.
They also called for data collection via multicentre registries that covered fertility outcomes, CAR–T cell kinetics, and comprehensive neonatal immune profiling.