Observational Cohort Study of People Living with HIV (PWH) Treated with CD19-Directed CAR T Cell Therapy for B-Cell Lymphoid Malignancies - Interim Results of AIDS Malignancy Consortium (AMC) Study AMC-113

Background: While non-Hodgkin lymphoma (NHL) are decreasing among PWH, NHL remains the leading cause of cancer-attributable deaths in PWH (Horner MJ, et al. Clin Infect Dis 2021) and the risk of NHL remains significantly increased in PWH (Engels EA, et al. Clin Infect Dis 2017). Nevertheless, PWH have been excluded based on Human Immunodeficiency Virus (HIV) status from landmark trials leading to FDA approval of all currently available CD19-directed CAR-T cell products for the management of relapsed or refractory B cell lymphomas. Therefore, information on safety and efficacy with this potentially curative treatment in PWH is limited to a few case reports. In this interim report of a collaborative effort between the AMC and the Center for International Blood and Marrow Transplant Research (CIBMTR), we aimed to fill this knowledge gap by describing patient and treatment characteristics and outcomes for PWH treated with CD19-directed CAR T cells.

Methods: This is a prospectively collected registry study using CIBMTR data of up to 30 patients (patients) diagnosed with HIV who received CD19 CAR T cell therapy (CAR-T) after 8/30/2017 for B cell lymphoid malignancies. Data on patient, HIV, and disease characteristics, treatment, as well as treatment-related outcomes and toxicities are being collected. Primary objectives are safety and efficacy of CD19 CAR T cell treatment; secondary outcomes include survival, and impact of CAR T cell therapy on HIV disease. Statistical analysis is exploratory and primarily descriptive. Efficacy is determined using CIBMTR Disease-Specific Manuals for response assessment (https://www.cibmtr.org/manuals/fim/1/en/topic/none). Treatment-related toxicities are described using the ASTCT Consensus Grading for Cytokine Release Syndrome (CRS) and Neurologic Toxicity Associated with Immune Effector Cells (ICANS), and the CTCAE v5.0 version. We summarized patient characteristics as follows: for categorical and ordinal variables, frequencies and percentages are calculated; for continuous variables, the mean, or median is reported. The distribution of time-to-event endpoints (overall survival (OS), progression free survival, duration of response) is presented using a Kaplan-Meier plot.

Results: As of data cut off on 7/11/2022 for the interim analysis, data on 21 patients from 13 centers are available. Median age is 55 years (range 29-70), 81% are male; 43% identified as White, and 38% as Black, 19% as Latinx. 95% (n=20) received axicabtagene ciloleucel and 5% (n=1) brexucabtagene autoleucel. All patients had NHL (n=1 follicular lymphoma, n=1 mantle cell lymphoma, n=19 large B cell lymphoma); 24% (n=5) had a prior auto transplant. Median time from HIV diagnosis to CAR-T was 117 months (range 14-490); median pre-CAR-T CD4 count was 228 cells/mm³ (range 0-252). HIV viral load pre-CAR-T is available for 10 patients and was <100 copies/ml in 8 (median 21 copies/ml, range 0-10x10⁶). CRS occurred in 9 patients (69%): Grade (G) 1 in 6 (46%) and G2 in 3 (23%), with a median CRS onset of 7 (2-10) days, and CRS resolution in 100% after a median of 4 (1-13) days. Neurotoxicity (ICANS) occurred in 3 patients (23%), n=2 G3, and n=1 G4, all of which resolved after a median of 5 (4-8) days. With a median follow up of 6 months (range 1-12), overall survival at 3 and 6 months were 83% (95%CI, 58-98) and 64% (95%CI, 35-89) respectively. Of the 4 patients who died, 3 died of disease progression, and 1 of a bacterial infection 6 months after CAR T cell infusion.

Conclusion: This is the largest series of PWH treated with CAR-T. Furthermore, our cohort includes 45% Black and Latinx patients who are underrepresented in CAR-T trials. In this interim analysis with limited follow up, CD19-CAR T cell therapy appears safe and efficacious in PWH similar to reports in people without HIV. The study is ongoing. AMC-112 is currently enrolling onto a prospective CAR-T study.

Barta:Kyowa Kirin: Consultancy, Honoraria; Daiichi Sankyo: Consultancy; Seagen: Honoraria; Janssen: Other: Independent Data Monitoring Committee member; Affimed: Consultancy; Acrotech: Honoraria. Noy:Janssen: Research Funding. Pasquini:Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Research Funding; Janssen: Research Funding; Kite: Research Funding. Baiocchi:CODIAK Biosciences: Research Funding; Atara Biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Viracta Therapeutics: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; eLife (Journal): Other: Editorial board.