Outcome of high-grade B-cell lymphoma compared to 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 (LBCL). 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 FISH, were collected from the French DESCAR-T registry. Between January 2018 and November 2022, 228 patients were included across 14 centers, 73 with HGBL (28 HGBL-DH MYC-BCL2, 14 HGBL-TH, 8 HGBL-DH MYC-BCL6, 23 HGBL-NOS) and 155 with non-HGBL. Median follow-up was 18.5 months [95% CI, 14.3-23.4] from the date of infusion. Progression-free survival (PFS) and overall survival (OS) were not significantly different between HGBL and non-HGBL, at respectively 3.2 months [95% CI, 2.8-6.0] vs 4.5 months [95% CI, 3.1-8.7] (p = 0.103) and 15.4 months [95% CI, 5.6-32.4] vs 18.3 months [95% CI, 8.5-NR]. 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 = 0.037). However, infused patients 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 earlier in the course of the disease.