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Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: An International, Multicenter, Retrospective Study. J Clin Oncol 2024 Mar 29:JCO2400033

Date

03/29/2024

Pubmed ID

38552193

DOI

10.1200/JCO.24.00033

Abstract

PURPOSE: Outcomes for Richter transformation (RT) are poor with current therapies. The efficacy and safety of anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) for RT are not established.

METHODS: We performed an international multicenter retrospective study of patients with RT who received CAR-T. Patient, disease, and treatment characteristics were summarized using descriptive statistics, and modeling analyses were used to determine association with progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated from the date of CAR-T infusion.

RESULTS: Sixty-nine patients were identified. The median age at CAR-T infusion was 64 years (range, 27-80). Patients had a median of four (range, 1-15) previous lines of therapy for CLL and/or RT, including previous Bruton tyrosine kinase inhibitor and/or BCL2 inhibitor therapy in 58 (84%) patients. The CAR-T product administered was axicabtagene ciloleucel in 44 patients (64%), tisagenlecleucel in 17 patients (25%), lisocabtagene maraleucel in seven patients (10%), and brexucabtagene autoleucel in one patient (1%). Eleven patients (16%) and 25 patients (37%) experienced grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, respectively. The overall response rate was 63%, with 46% attaining a complete response (CR). After a median follow-up of 24 months, the median PFS was 4.7 months (95% CI, 2.0 to 6.9); the 2-year PFS was 29% (95% CI, 18 to 41). The median OS was 8.5 months (95% CI, 5.1 to 25.4); the 2-year OS was 38% (95% CI, 26 to 50). The median duration of response was 27.6 months (95% CI, 14.5 to not reached) for patients achieving CR.

CONCLUSION: CAR-T demonstrates clinical efficacy for patients with RT.

Author List

Kittai AS, Bond D, Huang Y, Bhat SA, Blyth E, Byrd JC, Chavez JC, Davids MS, Dela Cruz JP, Dowling MR, Duffy C, Ho C, Jacobson C, Jaglowski S, Jain N, Lin KH, Miller C, McCarthy C, Omer Z, Parry E, Rai M, Rogers KA, Saha A, Schachter L, Scott H, Senapati J, Shadman M, Siddiqi T, Stephens DM, Vanguru V, Wierda W, Woyach JA, Thompson PA

Author

Samantha M. Jaglowski MD, MPH Professor in the Medicine department at Medical College of Wisconsin