CAR T-Cells Treatment for Relapsed/Refractory B-Cell Lymphoma Is Effective and Safe in People Living with HIV (PLWH): A Lysa Study from the Descar-T Registry

Background

Despite antiretroviral therapy (ART), people living with HIV (PLWH) have an increased risk for occurrence of lymphomas, and B-cell lymphomas remain the leading cause of AIDS-related deaths in the Western world. Moreover, given the improved life expectancy due to the use of combined ART, age-related lymphoid neoplasms are expected to be more frequently diagnosed in PLWH in the future. Although anti-CD19 chimeric antigen receptor T-cells (CAR T) represent a major advance in the treatment of relapsed/refractory (R/R) B-cell lymphomas, PLWH have been excluded from clinical trials. Here, we used the nationwide, real-life, DESCAR-T registry to describe clinical features and outcomes of PLWH patients diagnosed with lymphoma and treated with commercial CAR T therapy in France.

Methods

The analysis was conducted using the data export from DESCAR-T registry of 01/Apr/2024. Twenty-four HIV positive patients diagnosed with R/R B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel) were retrospectively identified from 15 Centers. Data on patient features, HIV status, hematologic disease and treatment characteristics, including toxicities and outcomes, were collected. Primary end points were efficacy (Lugano 2014, local assessment) and safety; secondary endpoints included progression free survival (PFS) and overall survival (OS). Due to the low sample size and heterogeneity, no direct statistic comparison between the PLWH cohort and the axi-cel DESCAR-T cohort analysis was made. The distribution of time-to-event endpoints (PFS and OS) is presented using a reverse Kaplan Meier on time to death.

Results

At time of data analysis, 24 patients received axi-cel. Histological subtypes included diffuse large B-cell lymphoma (n=20, 84%), follicular lymphoma (n=2, 8%), transformed follicular lymphoma (n=1, 4%) and grey zone lymphoma (n=1, 4%). Median age was 55 years (range 35-75), with 29% aged >60 years, and 71% were male. At time of CAR T-cell eligibility, 18 (90%, with n=4 missing values) had advanced disease (stage III/IV), the median number of previous treatment lines was 3 (range 1-4), and 4 (17%) had received a prior autologous stem cell transplantation. Median time from HIV diagnosis to CAR T was 136 months (range 11-342) and HIV viral load at lymphodepletion was undetectable in all available cases (11/24 patients). Bridging therapy was administered to 63% of patients (chemotherapy-based for 37% of patients), and 73% (n=11) were non responders. At time of CAR T infusion, 4 patients (17%) had ECOG PS ≥2, 15 (63%) elevated LDH, and 10 (42%) elevated ferritin. After dosing, cytokine release syndrome (CRS) occurred in 21 patients (88%) [1 (4%) of grade ≥3] with a median onset of 3 days (range 1-15) and complete resolution in all cases after a median of 6 days (range 1-10); immune-effector cell neurotoxicity syndrome (ICANS) occurred in 8 patients (33%) [3 (13%) of grade ≥3] with a median onset of 5.5 days (range 1-29) and complete resolution in all cases after a median of 5.5 days (range 2-10). Overall Response Rate (ORR) among PLWH at 90 days (M3) from axi-cel infusion was 50%, with 42% of Complete Response Rate (CRR). With a median follow-up of 10.5 months (95% CI, 6-16), PFS and OS at 12 months were 40% (95% CI, 18-61) and 55% (95% CI, 28-75) respectively. Ten deaths were reported: 8 patients died of disease progression, 1 of Pseudomonas infection, and 1 of progressive multifocal leukoencephalopathy not directly related to CAR T-cells.

Conclusions

To our knowledge, this is the largest series with the longest follow-up of PLWH lymphoma patients treated with axi-cel in real-life, from a single country. Sample size and inhomogeneity of population reflect the difficulties in treating these patients. Our study suggests that CAR T-cells are safe and efficient in PLWH. These results should be considered to avoid treatment disparities and to start including PLWH into clinical trials.