Outcomes of CAR-T therapy in HIV-positive multiple myeloma patients: A retrospective database analysis

Abstract Background: Chimeric antigen receptor T-cell (CAR-T) therapy has redefined treatment for patients with relapsed/refractory multiple myeloma (MM) and is now considered standard of care in relapsed/refractory setting. However, patients with Human Immunodeficiency Virus (HIV) were excluded in the clinical trials leading to the regulatory approval, which shows a critical gap of knowledge and leaves a major question unanswered regarding their outcomes with this revolutionary treatment. Studies have shown that patients with HIV who undergo transplant therapies, such as autologous or allogenic stem cell transplant, tolerate it without increased complications and with comparable survival benefits. Despite this, outcomes for HIV patients are frequently extrapolated from non-HIV populations, leading to uncertainty in real-world clinical decision-making and limiting treatment options. To our knowledge, this is the first study that aims to evaluate the influence of HIV infection in the outcomes of patients treated with CAR-T with a diagnosis of MM. Methods: A retrospective database review was performed using the TriNetX Research Network, a federated network of HIPPA compliant de-identified data from multiple Health Care Organizations (HCO) from the Global Collaborative Network. Adult patients (≥18 years) with MM and HIV were included, provided their MM diagnosis occurred after HIV diagnosis. The time constraint limitation to include only cases occurring after January 1st 2021 was unable to be carried out due to the limitation on the filters. Outcomes for patients with and without HIV were compared after cohort balancing. Kaplan-Meier survival curves were used to assess overall survival. Incidence of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), sepsis and opportunistic infections were evaluated using odds ratios with 95% confidence intervals. Results: A total of 2,185 who had MM and underwent a CAR-T were identified from 45 HCO, of these, 26 patients had a diagnosis of HIV. It was not possible to differentiate between which patients received Lisocabtagene maraleucel and ciltacabtagene autoleucel. Patients with HIV tend to have a younger age at index event, with 61.6 years vs 64.0 years compared to those with non-HIV. No difference in sex, race or ethnicity was noted between cohorts. No statistical difference was evidenced on baseline laboratory values including blood counts, hepatic and renal function, and inflammatory markers including lactate dehydrogenase, ferritin, c-reactive protein and erythrocyte sedimentation rate. Patients with HIV had a higher risk for ICANS of 44% vs 14% [OR of 4.811, 95% CI: 2.088,11.081] but were not at an increased risk for CRS, as these represented 44% for HIV vs 47% for non-HIV. A higher incidence of sepsis and opportunistic infections was noted in HIV patients, with 44% vs 15% [OR 4.534 95% CI: 1.969, 10.439] and 21.5% vs 18.1% [OR of 1.235 95% CI: 0.902,1.689], respectively. The later was defined as pneumocystis pneumonia, toxoplasmosis, cytomegalovirus, tuberculosis, candidiasis, cryptococcosis, histoplasmosis, herpes simplex virus, progressive multifocal leukoencephalopathy and mycobacterium avium complex. Patients with HIV were more likely to receive GCSF [OR 2.309, 95% CI: 0.946,5.638]. The usage of intravenous immunoglobulin was unable to be determined. Overall survival was significantly inferior among patients with HIV [p<0.0001], with a median survival time in days of 906 vs 2,072 in those patients without HIV. Conclusion: This study highlights an urgent, unmet need: although patients with HIV represent a small subset of those undergoing CAR-T for MM, they may be at elevated risk for therapy-related toxicities and infections, which in turn could contribute to poorer survival outcomes. While limited by small sample size, these findings emphasize the importance of including HIV patients in clinical trials for novel cancer therapies. Doing so would enable development of tailored approaches, such as enhanced monitoring for CRS/ICAN-related inflammation and broader infectious prophylaxis strategies, which could mitigate risk and improve outcomes.