Effectiveness of CAR-T Therapy in Double-Hit and Double-Expressor Lymphomas

Relapsed or refractory (R/R) double-hit lymphoma (DHL; high-grade [non-Hodgkin] B-cell lymphoma [HGBCL] with MYC and BCL2 and/or BCL6 rearrangements) and double-expressor lymphoma (DEL; overexpression of MYC and BCL2 on immunohistochemistry) are distinct subtypes of diffuse large B-cell lymphoma (DLBCL) with inferior responses to chemoimmunotherapy and autologous stem-cell transplantation. Chimeric antigen receptor T-cell (CAR-T) therapy leads to similar overall response rates (ORRs) for both DHL and non-DHL, while the duration of response for DHL and DEL remains unknown. A multicenter retrospective analysis evaluating post‒CAR-T progression and survival outcomes in patients with DHL versus non-DHL, as well as DHL versus DEL versus other, was performed. Findings were reported at the 64th American Society of Hematology Annual Meeting and Exposition.

A total of 536 adult patients with R/R HGBCL were treated with anti-CD19 CAR-T therapy from 2015 to 2021 in 13 US centers. Baseline characteristics were compared among cohorts with a Pearson chi-square test, including several patient and disease characteristics, treatment history, and history of adverse events. Median progression-free survival (mPFS) and median overall survival (mOS) were estimated using the Kaplan-Meier method. Variables of clinical significance and those associated with PFS on univariate analysis were incorporated into a Cox multivariable regression analysis (MVA) to determine their impacts on CAR-T PFS.

A total of 408 patients were included in the DHL (n = 80) and non-DHL (n = 328) cohorts; 64% received axicabtagene ciloleucel, 26% received tisagenlecleucel, and 10% received lisocabtagene maraleucel. Clinical characteristics were similar, except DHL versus non-DHL patients were more likely to have germinal center B-cell (GCB) cell-of-origin (P <.001), elevated lactate dehydrogenase (LDH) at diagnosis (P = .02), and history of receiving CAR-T in the second-line setting (P = .02). Median follow-up from time of CAR-T was 17.7 months in surviving patients. CAR-T ORR was similar for DHL versus non-DHL (69% vs 66%), as were complete response (CR) rate (49% vs 48%), mPFS (7.5 vs 6.2 months), and mOS (not reached [NR] vs 21 months); on MVA, there was no difference in CAR-T PFS. In those progressing post‒CAR-T (DHL, n = 35; non-DHL, n = 175), patients with DHL had inferior mOS versus non-DHL patients from the time of CAR-T progression (2.7 vs 6.0 months, P = .02). Patients with DHL received therapy at a similar rate as non-DHL patients following CAR-T progression (54% vs 67%) and had similar median time to relapse post‒CAR-T (2.9 months).

A total of 333 patients were included in the DHL (n = 80), DEL (n = 74), and other (n = 179) cohorts. Clinical characteristics were similar for DHL versus DEL versus other, except for bulky disease at diagnosis (P = .01), elevated baseline LDH (P = .006), bridging therapy (P = .02), and GCB type (P <.001). Median follow-up from CAR-T was 18.7 months. CAR-T ORR was similar for the DHL versus DEL versus other cohorts (69% vs 64% vs 66%), as were CR rate (49% vs 42% vs 48%), mPFS (7.5 vs 6.2 vs 9.0 months), and mOS (NR vs 19.1 vs 25.7 months); on MVA, there was no difference in CAR-T PFS. In patients progressing post‒CAR-T (DHL, n = 35; DEL, n = 46; other, n = 92), mOS was similar among patients with DEL and others (6.0 vs 5.8 months).

In conclusion, mPFS and mOS of patients with R/R DHL and DEL treated with CAR-T mirrored those observed in other patients with DLBCL, supporting early use of CAR-T in these high-risk patients.

Source

Zurko J, Shouse G, Torka P, et al. Double hit/double expressor lymphomas: a multicenter analysis of survival outcomes with CD19-directed CAR T-cell therapy. Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Oral presentation 154.