New data from a phase 1/2 study presented at the Transplantation & Cellular Therapy Meetings show that the bispecific CAR T-cell therapy LV20.19 is highly effective for patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL), but it also brings important safety concerns.
In the study of 18 patients who had received a median of four prior treatments, 78% achieved a complete response. The median progression-free survival was 32 months, and 79% of patients were still alive at 24 months. Seven patients achieved minimal residual disease (MRD) negativity within the first 90 days, suggesting deep and durable remissions.
However, side effects were common. Cytokine release syndrome occurred in 94% of patients, although most cases were mild. About 22% experienced neurotoxicity (ICANS). Notably, 50% developed a serious immune-related condition known as IEC-HS, which resembles hemophagocytic lymphohistiocytosis (HLH). This rate is much higher than in other B-cell cancers and may be linked to the high levels of circulating cancer cells typical in CLL. Many patients required medications such as Tocilizumab, steroids, and Anakinra to control inflammation.
The therapy includes several innovations. It targets both CD19 and CD20 to reduce the risk of the cancer escaping treatment. The manufacturing process was shortened to 8 to 12 days, and enhanced cytokine support was used to improve CAR T-cell expansion and persistence after infusion.