End of phase I results of ZUMA-3, a phase 1/2 study of KTE-X19, anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in adult patients (pts) with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL).
2019; Lippincott Williams & Wilkins; Volume: 37; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2019.37.15_suppl.7006
ISSN1527-7755
AutoresBijal Shah, Michael Bishop, Olalekan O. Oluwole, Aaron C. Logan, Maria R. Baer, William B. Donnellan, Kristen Marie Carr-O'Dwyer, Houston Holmes, Martha Arellano, Armin Ghobadi, John M. Pagel, Yi Lin, Ryan D. Cassaday, Jae Hong Park, Armen Mardiros, Tong Shen, Lovely Goyal, Remus Vezan, Rajul K. Jain, William G. Wierda,
Tópico(s)CAR-T cell therapy research
Resumo7006 Background: KTE-X19 is an autologous anti-CD19 CAR T cell therapy under investigation for adult R/R ALL. In an interim analysis of Phase 1 of ZUMA-3, we reported manageable safety and encouraging efficacy of KTE-X19; 72% of pts achieved a complete remission (CR) or CR with incomplete bone marrow (BM) recovery (CRi; Wierda et al, ASH 2018. #897). Here, we present end of Phase 1 results. Methods: Adults with R/R B cell ALL, > 5% BM blasts, and ECOG 0-1 received 2, 1, or 0.5 × 10 6 KTE-X19 cells/kg after conditioning chemotherapy. Revised adverse event management (rAE mgmt) was implemented for additional pts in a 1 × 10 6 dose cohort: corticosteroids were given earlier at onset of Grade ≥ 2 neurologic events (NEs) and tocilizumab was used only for active toxicity. The primary endpoint was the dose-limiting toxicity (DLT) rate. Key additional endpoints were KTE-X19 levels, incidence of AEs, minimal residual disease (MRD), and CR/CRi rate. Results: As of 9/27/18, 45 pts had received KTE-X19 (median follow-up [f/u], 16 mo). The median age was 46 y (range, 18–77); 30 pts (66%) had ≥ 3 prior therapies and the median pre-conditioning BM blasts was 70% (range, 0–97). Six, 23, and 16 pts received 2, 1, and 0.5 × 10 6 cells/kg, respectively. There were no DLTs in the DLT-evaluable pts. The most common Grade ≥ 3 AEs were hypotension (38%), pyrexia (38%) and thrombocytopenia (31%). There were 2 previously reported KTE-X19–related Grade 5 AEs of cerebral infarction and multiorgan failure, both in the context of CRS. Grade ≥ 3 CRS and NEs occurred in 13 (29%) and 17 (38%) pts, respectively. Of 41 pts with ≥ 2 mo of f/u, 68% had CR/CRi, and 73% had undetectable MRD. Of 19 pts with ≥ 2 mo of f/u treated with 1 × 10 6 cells/kg, 16 (84%) had a CR/CRi and the median event-free survival was 15 mo. In 9 pts treated with 1 × 10 6 cells/kg and rAE mgmt, 2 (22%) had Grade 3 CRS and 1 (11%) had Grade 3 NE with no Grade 4/5 events. Conclusions: KTE-X19 dosing and safety mgmt have been successfully refined by testing 3 cell doses and evaluating a new AE mgmt guideline with altered corticosteroids/tocilizumab use for NE/CRS. Pivotal Phase 2 is ongoing at the 1 × 10 6 dose with rAE mgmt. Clinical trial information: NCT02614066.
Referência(s)