Improved Outcomes Associated With CD19-Specific CAR-T Therapy in CLL Patients

In a recent study, researchers examined the outcomes of patients with chronic lymphocytic leukemia (CLL) treated with CD19-specific Chimeric antigen receptor T-cell (CAR-T) therapy—specifically focusing on overall survival and progression following CART-T treatment.

“This data sets a benchmark for clinical trials that intend to improve outcome of CLL patients with progression after CAR-T,” explained Mazyar Shadman, MD, MPH, department of medicine, University of Washington, and the clinical research division, Fred Hutchinson Cancer Research Center, Seattle, WA, and colleagues.

The study comprised CLL patients treated with CD19-specific CART-T. Researchers utilized multivariable models including variables related to disease, treatment, and CAR-T procedure in order to establish a benchmark.

Of 28 patients identified, 16 experienced stable or progressive disease, and 12 experienced relapsed disease after CAR-T therapy. 

The study results revealed the following:

• Five patients had prior allo-SCT;
• Bridging therapy was used in five patients after leukapheresis; 
• Adverse events among 22 patients receiving CAR-T included CRS, and NT in 7 patients
• After CAR-T, 5 patients receiving Venetoclax had a median duration of response of 5 months;
• Patients treated with Ibrutinib with a duration of response of 2 months in pre-CAR-T IB failed versus 12.25 months in pre-CAR-T IB responsive patients;
• Fourteen patients had repeat CAR-T therapy with duration of response after second CAR-T of 5.5 months;
• Roughly 6.5 months after CAR-T progression, sic patients received allo-SCT;
• There was a strong link between history of progression on both IB and Ven before CAR-T with poor OS; and
• Patients who received an all-SCT following CAR-T experienced improved OS.

“Overall survival after CAR-T progression was significantly shorter in patients who received CAR-T after failing both ibrutinib and venetoclax compared to others,” concluded the researchers. “This finding supports referring high-risk CLL patients for CAR-T treatment after progression on ibrutinib and while still responsive to venetoclax.” —Edan Stanley