CD19-directed CAR T-cell therapy for B-cell lymphoid malignancies is safe and effective in people living with HIV (PWH) – a matched cohort analysis by the center for international blood and marrow transplant research (CIBMTR) and the AIDS malignancy

Abstract Background: Despite a decreasing incidence, NHL remains the leading cause of cancer-attributable deaths in PWH (Horner MJ, et al. Clin Infect Dis 2021). Nevertheless, PWH were excluded based on their HIV status alone from trials leading to the FDA approval of the currently available CD19-directed CAR-T cell (CART19) products for relapsed or refractory B-cell lymphomas. Thus, information on safety and effectiveness of this potentially curative treatment has been largely limited to few published case reports. In this collaborative effort between the AMC and the CIBMTR, we determined outcomes of PWH who received CART19 therapy and compared them with a matched cohort of people without HIV. Methods: We prospectively collected data on 35 patients (pts) diagnosed with HIV who received CART19 therapy between 8/30/2017 and 11/05/2024 for B-cell lymphoid malignancies. Data on patient, HIV, and disease characteristics, treatment, treatment-related outcomes and toxicities were collected. We next created a matched cohort of 135 pts without HIV (HIV-) who underwent CART19 therapy during the same period matched on key clinical factors (age, performance score, NHL subtype, CART19 product, and disease status pre-CART). Outcomes compared included Cytokine Release Syndrome (CRS), Neurologic Toxicity Associated with Immune Effector Cells (ICANS), disease response, hematologic recovery, progression-free survival (PFS), and overall survival (OS). To account for matching, a marginal univariable Cox model (OS, PFS) and a marginal univariable Fine-Gray model (CRS, ICANS, hematological recovery, complete and overall response) were used for calculating and comparing survival probabilities and cumulative incidences, respectively, between both cohorts. Results: A total of 170 pts were included in this analysis (35 HIV+, 135 HIV-). The cohorts were matched for age (median age: HIV+ 56 years (y) (range 29-69); HIV- 57y (24-73)); disease subtype (DLBCL: 91%; FL: 6%; and MCL: 3%, each); CART19 product (axi-cel 97%; brexu-cel 3%, each); and response prior to CART19 (CR 3% each; PR 14% each; relapse/resistant 62.9% vs 60.7%; relapse untreated 2.9% vs 4.4%; relapse chemosensitive 8.6% vs 13.3%; relapse sensitivity unknown 8.6% vs 4.4%). The HIV+ cohort included more men (88.6% vs. 55.6%, p<0.01), more Blacks (25.7% vs 8.1%, p<0.01), and more people seropositive for HepB (17.1% vs 0%, p<0.01) or HepC (8.6% vs 0%, p<0.01). In addition, there were differences that did not achieve statistical significance: bendamustine lymphodepletion (17.1% vs 8.9%, p=0.22) and bridging therapy (62.9% vs 48.1%, p=0.15) were more common in the HIV+ cohort. For PWH, the median time from HIV diagnosis to CART19 was 132 months (1.6-490.0). Median pre-CART19 CD4 count was 191 cells/mm3 (0-252) and median pre-CART HIV viral load (VL) 20 copies/ml (0-10x106); only 11.4% had a HIV VL >400 copies/ml. CRS occurred less commonly in the HIV+ cohort (any grade 68.6% vs 82.2%, p=0.04). ICANS was comparable (any grade 22.9% vs 44.4%, p=0.17). Bacterial infections at 100 days were more common in PWH (28.6% vs. 10.4%, p<0.01). Median follow-up for survivors was 14.5 mo for the entire cohort. At 100 days, neutrophil recovery was similar (91.7% vs 94.8%; p=0.33) with delayed platelet recovery in PWH (71.1% vs 80.4% p=0.06). Cumulative incidence at 6 months of overall response (42.6% vs. 65.8%, p=0.013) and complete response (34.6% vs. 57.4%, p=0.021) was lower in PWH. PFS was not significantly different between cohorts (1-and 2-year PFS: 36.1%/28.3% (HIV+) vs 51.1%/43.6% (HIV-); p=0.103), but OS was lower in PWH (1- and 2-year OS 45.7%/37.3% (HIV+) vs 65.9%/59.7% (HIV-); p=0.016). There was no difference in treatment-related mortality (TRM; p=0.197). The primary cause of death was PD (94.7% (HIV+) vs 73.9% (HIV-) followed by infections (5.3% vs 6.5%) in both cohorts.Conclusion: CART19therapywas safely administered in this large prospective cohort of PWH with 28.3% alive and in remission at 2 years from therapy. Compared to a matched HIV- cohort, toxicities were mostly similar except for more infections in PWH. The lower OS and responses for PWH was driven by lymphoma-related features rather than TRM. Notably, the HIV+ cohort contained a larger proportion of Black patients who are commonly underrepresented in clinical trials and may represent a clinically distinct entity with worse outcomes (Lee MJ, et al. Cancer 2020). AMC-112 is currently enrolling onto a prospective CART19 study.