Outcome of high-grade B-cell lymphoma compared with other large B-cell lymphoma after CAR-T rescue: a DESCAR-T LYSA study.

High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (double hit [HGBL-DH] or triple hit [HGBL-TH]) or not otherwise specified (HGBL-NOS) are considered to be more aggressive diseases among large B-cell lymphomas (LBCLs). CD19-targeting chimeric antigen receptor (CAR) T cells have changed the prognosis of chemoresistant LBCL. Clinical and pathological data of patients treated for relapsed/refractory LBCL or HGBL in third line or more, all characterized by fluorescence in situ hybridization, were collected from the French DESCAR-T registry. Between January 2018 and November 2022, a total of 228 patients were included across 14 centers, 73 with HGBL (28 HGBL-DH MYC-BCL2, 14 HGBL-TH, 8 HGBL-DH MYC-BCL6, and 23 HGBL-NOS) and 155 with non-HGBL. The median follow-up was 18.5 months (95% confidence interval [CI], 14.3-23.4) from the date of infusion. Progression-free survival and overall survival (OS) were not significantly different between HGBL and non-HGBL, at 3.2 months (95% CI, 2.8-6.0) vs 4.5 months (95% CI, 3.1-8.7; P = .103) and 15.4 months (95% CI, 5.6-32.4) vs 18.3 months (95% CI, 8.5 to not reached), respectively. From the date of eligibility, the median OS was inferior for patients with HGBL-TH/DH MYC-BCL2 at 6.6 months vs 18.5 months for HGBL-NOS vs 13.6 months for HGBL-DH MYC-BCL6 vs 11.8 months for LBCL (P = .037). However, patients who received infusion presented the same outcome. CAR T-cell therapy used in third line or more seems to overcome the poor prognosis of HGBL subtypes, especially in HGBL-TH/DH MYC-BCL2. This observation supports considering the potential benefit of using CAR T cells earlier in disease course.