Tecartus (brexucabtagene autoleucel)

Brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, is a promising and available salvage option for relapsed/refractory philadelphia-positive B-Cell Acute Lymphoblastic Leukemia patients, potentially effective even after several previous lines of therapy and a previous allogeneic stem cell transplant (HSCT). This reported clinical case allowed us to highlight different relevant factors for the optimal, complex and multidisciplinary management of this subgroup of patients: bridging therapy selection, the need of reevaluating CD19 expression, disease burden as an outcome predictor and the role of HSCT as a further therapeutic consolidation.

P2, N=25, Active, not recruiting, Kite, A Gilead Company | Trial primary completion date: Jul 2027 --> Nov 2025

IEC-HS is a rare but potentially fatal complication. Our disproportionality analysis identifies significant reporting signals for tisa-cel and cilta-cel. The high absolute number of cases observed for products like axi-cel appears to reflect high utilization rather than a disproportionate risk, underscoring the necessity of using statistical signal detection methods when interpreting spontaneous reports.

This paper presents a case of a 56-year-old woman with relapsed mantle cell lymphoma (MCL) treated with the CAR-T cell therapy, brexucabtagene autoleucel, who had subsequently developed CRS and later IEC-HS. Initial management included tocilizumab, corticosteroids, and anakinra, followed by the compassionate use of emapalumab, an interferon-γ blocker...Vigilant monitoring and tailored therapeutic approaches are required to effectively manage toxicities associated with CAR-T cell therapy, to maximize its benefits and minimize adverse effects. In more severe IEC-HS cases, emapalumab may be used as an effective targeted therapy.

P2, N=95, Completed, Kite, A Gilead Company | Trial primary completion date: Nov 2024 --> Jun 2025

Brexucabtagene autoleucel (brexu-cel) is the anti-CD19 CAR-T therapy approved for the treatment of relapse/refractory (RR) mantle cell lymphoma (MCL)...Forty-nine patients received salvage therapy: 16 lenalidomide ± rituximab (Len/R2), 13 immunochemotherapy (ICT), 8 Bruton tyrosine kinase inhibitor ± venetoclax (BTKi/Ven), 7 a bispecific T-cell engager (TCE), 3 another targeted therapy, and 2 radiations...Notably, none of the TCE responders have relapsed to date (DOR of 100%). Our series highlights the poor outcomes of MCL patients following CAR-T failure and suggest a potential benefit of bispecific antibodies in this population.

P1/2, N=95, Active, not recruiting, Kite, A Gilead Company | Trial primary completion date: Sep 2024 --> Feb 2026

P1, N=8, Active, not recruiting, Stanford University | Recruiting --> Active, not recruiting | N=20 --> 8 | Trial completion date: Aug 2025 --> Jun 2027 | Trial primary completion date: Aug 2025 --> Jun 2027

P1, N=22, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Modern immunotherapy in the form of T‑cell-based CD19-targeted approaches, such as the approved bispecific T‑cell engager (BiTE antibody) blinatumomab and chimeric antigen receptor T cells (CAR T cells) with the approved products tisagenlecleucel and brexucabtagene autoleucel has revolutionized the treatment of B‑precursor acute lymphoblastic leukemia (ALL). Furthermore, resistance mechanisms are discussed and an outlook on further development is given. The T‑precursor ALL remains a challenge due to its immunological complexity but new developments in CAR-T cell treatment approaches targeting CD5 and CD7 show that progress is also being made in this area.

P2, N=95, Completed, Kite, A Gilead Company | Active, not recruiting --> Completed

P2, N=25, Active, not recruiting, Kite, A Gilead Company | Recruiting --> Active, not recruiting