C091 | Patients With Relapsed/refractory Pmbcl Have Better Survival When the Salvage Strategy Includes Car T-cells: an Analysis of the Reprime-fil and the Cart-sie Studies
Year: 2025
Type: article
Abstract: Introduction Salvage treatment of relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL) patients (pts) has been revolutionized by the use of Chimeric Antigen Receptor (CAR) T-cell therapy targeting CD19. This study aims to compare overall survival (OS) between R/R PMBCL pts treated with CAR T-cells and pts treated with salvage programs not including CAR T-cells. Methods We performed a pooled analysis including all pts affected by PMBCL enrolled in the ongoing multicenter prospective observational study CART-SIE (NCT06339255) and in the retrospective REPRIME-FIL study (NCT05162170). CART SIE study collected data from pts treated with in-label anti-CD19 CAR T cells (CAR pts), whereas REPRIME study collected data from R/R PMBCL pts who received standard immune and chemotherapeutic salvage in the preCART era (noCAR pts). Pts with available data regarding date of first line failure, salvage treatments and follow-up were included. A landmark analysis at 6 months from the time of first line failure was performed. Results A total of 191 pts were considered eligible, 87 CAR pts and 104 noCAR pts were included in the pooled analysis, median age at diagnosis was 33 (IQR, 26-42) and 33 years (IQR, 26-41), respectively. Pts refractory to the first line (PFS less than or equal to 6 months) were 44 (51%) and 48 (46%), median lines of salvage regimens were 3 (range, 2-7) and 2 (range 0-3) in CAR e noCAR pts. Use of Check Points inhibitors (CPI) as line of salvage regimens was more frequent in CAR pts (55% vs 10%), whereas autologous stem cell tansplant was more frequently used in noCAR pts (49% vs 19%). Fifteen pt (17%) died in CAR group and 57 pts (55%) in noCAR group. The 2-years OS from the failure of first line treatment for the entire cohort was 62% (95% CI 55-69). The 6-month landmark analysis showed a significantly better OS for CAR pts compared to noCAR pts (Fig.1) (HR 0.35, 95%CI 0.18-0.67, p =0.002). In the multivariable analysis CAR T treatment was confirmed as significant predictor of OS (HR 0.34, 95%CI 0.17-0.66, p=0.001), whereas no differences in OS were observed according to sex, age and R/R status. Subgroup analysis showed no evidence of effect modification of CAR T according to sex, age (<40, ≥40 years) and R/R status. Conclusions R/R PMBCL patients have better OS when CAR T are employed for salvage. Given that CPI were frequently used as salvage treatment in CAR pts, their role should be further clarified in future studies.
Authors: A. Guidetti, I. Dogliotti, A. Chiappella, E. Iannitto, A. Evangelista, A. Dodero, A. Di Rocco, M. Balzarotti, B. Casadei, F. Cavallo, A. Re, M. Farina, S. Bramanti, P. Chiusolo, M. Martino, M. Musso, M. Zanni, G. Grillo, E. Ravano, M. Krampera, S. Hohaus, M. Martelli, M. Ladetto, C. Visco, P.L. Zinzani, U. Consoli, P. Corradini
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123029
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