Chimeric antigen receptor (CAR)-T cell therapy for Richter's transformation

Shaomei Feng^1,2,3Peihao Zheng^1,2,3Haidi Liu^1,2,3Meiling Sun^1,2,3Yuelu Guo⁴Lixia Ma⁴Rui Liu⁴Zhonghua Fu⁴Fan Yang⁴Xiaoyan Ke⁴Kai Hu^5*

• ¹Department of Myeloma and Lymphoma, Beijing GoBroad Boren Hospital, Beijing, China
• ²Beijing Branch Center of the Institute of Hematology & Blood Diseases Hospital, Beijing, China
• ³Myeloma Research Institute Beijing GoBroad Boren Hospital, Beijing, China
• ⁴Department of Lymphoma and Myeloma Research Center, Beijing GoBroad Hospital, Beijing, China
• ⁵Department of Hematology and Lymphoma Research Center, Beijing Gobroad Boren Hospital, Beijing, China

Background/purpose: Despite advances in chronic lymphocytic leukemia treatment, effective therapies for cases with Richter's transformation (RT) are urgently needed.This study aimed to investigate the use of chimeric antigen receptor (CAR)-T cell infusion for RT.Methods: This study included RT patients at Beijing Boren Hospital between February 2020 and February 2023. Complete response (CR), partial response (PR), overall response rate (ORR), overall survival (OS), progression free survival (PFS), and adverse events were analyzed.Results: Data from 16 patients with RT who underwent CAR-T cell therapy [62.5% (10/16) males and a median age of 59 years (range: 42-69 years)] were collected. The 3-month CR rate was 56.3% (9/16), with an ORR of 68.8% (11/16). Median followup was 19.1 months (4.37-42.48m), the 1-year OS/PFS were 75.0%/68.8%, and the 2year OS/PFS were 67.5%/61.1%. Among 11 patients with CR (n=9) and PR (n=2), 1 CR case died of an acute coronary event, 10 patients had no recurrence or progression at a median follow-up of 24.6 months. Five patients who did not respond to CAR-T cell therapy had a median OS of only 6.44 months. Univariate logistic regression analysis showed ECOG score [odds ratio (OR)=0.025, P=0.016] were independently associated with ORR. ECOG (OR=40, P=0.016) were independently associated with OS. The presence of an extramedullary mass larger than 5cm did not show statistical significance for overall survival (OS), although the P value was close to 0.05 (OR=15, P=0.051).Conclusions: CAR-T cell therapy showed potential as a treatment for RT. ECOGscore may be independently associated with ORR and OS. RT patients may experience prolonged remission and achieve long-term disease control if they attain remission through chimeric antigen receptor T-cell therapy.