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Fumou Sun, Ph.D..; Yan Cheng, Ph.D..; Carolina Schinke, M.D.
Publications
| Bispecific BCMA/CD24 CAR T cells control multiple myeloma growth
Nature Communications
January 2024
Primary authors: Fumou Sun, Ph.D.; Yan Cheng, Ph.D.
Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR T-cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse. Residual myeloma cells following BCMA-CAR-T-mediated treatment show less-differentiated features and express stem-like genes, including CD24. CD24-positive myeloma cells represent a large fraction of residual myeloma cells after BCMA-CAR-T therapy. In this work, we develop CD24-CAR-T cells and test their ability to eliminate myeloma cells. We find that CD24-CAR-T cells block the CD24-Siglec-10 pathway, thereby enhancing macrophage phagocytic clearance of myeloma cells. Additionally, CD24-CAR-T cells polarize macrophages to a M1-like phenotype. A dual-targeted BCMA-CD24-CAR-T exhibits improved efficacy compared to monospecific BCMA-CAR-T-cell therapy. This work presents an immunotherapeutic approach that targets myeloma cells and promotes tumor cell clearance by macrophages.
Teclistamab in relapsed refractory multiple myeloma: multi-institutional real-world study
Blood Cancer Journal
March 2024
Primary authors: Meera Mohan, M.D. (Medical College of Wisconsin); Jorge Monge, M.D. (Weill Cornell Medicine); Nishi Shah, M.D. (Montefiore-Einstein).
Supervisory author: Carolina Schinke, M.D. (UAMS College of Medicine)
The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of teclistamab up until August 2023. One hundred and ten patients were included, of whom, 86% had triple-class refractory disease, 76% penta-refractory disease, and 35% had prior exposure to B-cell maturation antigen (BCMA)-targeting therapies. The overall response rate (ORR) in our cohort was 62%, with a ≥ very good partial remission (VGPR) rate of 51%. The ORR in patients with and without prior BCMA-targeted therapies was 54% versus 67%, respectively (p = 0.23). At a median follow-up of 3.5 months (range, 0.39–10.92), the estimated 3-month and 6-month progression free survival (PFS) was 57% (95% CI, 48%, 68%) and 52% (95% CI, 42%, 64%) respectively. The incidence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) was 56% and 11% respectively, with grade ≥3 CRS and ICANS noted in 3.5% and 4.6% of patients respectively. Seventy-eight unique infections were diagnosed in 44 patients, with the incidence of all-grade and grade ≥3 infections being 40% versus 26% respectively. Primary prophylaxis with intravenous immunoglobulin (IVIG) was associated with a significantly lower infection risk on multivariate analysis (Hazard ratio [HR] 0.33; 95% CI 0.17, 0.64; p = 0.001). The main message is that all patients who receive teclistamab should receive prophylactic IvIG to mitigate the risk of infection.