CD19 CAR T-Cell Therapy Offers Hope for Patients wiht richter Conversion
A recent multicenter retrospective analysis demonstrates teh potential of anti-CD19 CAR T-cell therapy as a viable treatment option for patients with Richter transformation (RT), a notably aggressive subtype of lymphoma. published in the Journal of Cell and Molecular Medicine in 2025, the study analyzed outcomes for 54 patients treated with CAR T-cells, revealing promising activity despite the historically poor prognosis associated with RT.
Conventional chemoimmunotherapy for RT typically yields complete remission rates of 30% or less, with a median overall survival of under 12 months. This new research suggests CAR T-cell therapy can offer a meaningful betterment.
The study population received a combination of commercially available and academically produced CAR T-cell products. Tisagenlecleucel was the most frequently used (37%), followed by a Sheba point-of-care product (34%), ARI-0001 (20%), axicabtagene ciloleucel (7%), and lisocabtagene maraleucel (2%). Importantly, response rates were consistent across thes different CAR T-cell platforms.
Researchers identified several factors impacting patient outcomes. Lack of early response ( P* = .001) and older age (P* =.05) were independent predictors of mortality. Elevated lactate dehydrogenase (LDH) (P* = .005), high ECOG performance status (P* < .001), development of immune effector cell-associated neurotoxicity syndrome (ICANS) (P* = .046), and absence of response at one month (P* = .02) were also associated with inferior survival. Notably, genetic alterations such as del 17p, TP53 mutation, and IGHV status did not correlate with treatment response.
Safety data revealed that cytokine release syndrome (CRS) occurred in 87% of patients, with 21% experiencing grade 3 or 4 events. ICANS was observed in 22% of patients, 42% of whom experienced high-grade toxicity. Academic CAR T-cell products were linked to significantly higher rates of toxicities compared to commercial products – 60% experiencing CRS, ICANS, or infections within 30 days versus 40% for commercial products (P* = .04). Infections occurred in 41% of the entire cohort, with bacterial pathogens responsible for 68% of documented cases.
the role of allogeneic stem cell transplantation (alloSCT) following CAR T-cell therapy was also investigated. Only 7 of 54 patients (13%) underwent alloSCT – 4 as consolidation during remission and 3 for relapse or progression. Median progression-free survival (PFS) was 6.5 months for those receiving alloSCT compared to 8 months for those who did not (P* = .46). Among those who received alloSCT, 57% (4 of 7) died, with 3 deaths attributed to transplant-related toxicities and 1 to progressive disease.
The authors emphasize the importance of early response,stating that “depth and timing of response,particularly at 1 month,were the strongest predictor of durable benefit,suggesting this may be a key decision point in aiding further therapeutic planning.”
“This study adds valuable insights into the efficacy and safety of anti-CD19 CAR T-cells in patients with RT,” the authors conclude. While outcomes remain less favorable than those seen in de novo diffuse large B-cell lymphoma, CAR T-cell therapy “represents a meaningful and effective treatment option for this challenging disease.”
Reference:
Beyar-Katz O, Benjamini O, Delgado J, et al. CD19 CAR T-cell therapy in Richter transformation: A multicentre retrospective analysis by the European Research Initiative on chronic Lymphocytic Leukaemia. J Cell Mol Med. 2025;29(20):e70841. doi:10.1111/jcmm.70841
Thompson PA, Siddiqi T. Treatment of Richter’s syndrome. Hematology Am Soc hematol Educ Program. 2022;2022(1):329-336. doi:10.1182/hematology.2022000345
