Updated Phase 1 Results of Zuma-3: Kte-X19, an Anti-CD19 Chimeric Antigen Receptor T Cell Therapy, in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia

• Published in: Biology of blood and marrow transplantation 2019-03, Vol.25 (3), p.S185-S185
• Main Authors: Wierda, William G, Bishop, Michael R., Oluwole, Olalekan, Logan, Aaron C., Baer, Maria R., Donnellan, William B., O'Dwyer, Kristen M., Castro, Januario E., Schiller, Gary J., Holmes, Houston, Abedi, Mehrdad, Ghobadi, Armin, Arellano, Martha L., Malone, Adriana K., Pagel, John M., Mardiros, Armen, Shen, Tong, Vezan, Remus, Jain, Rajul K., Shah, Bijal D.
• Format: Article
• Language: English
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2018.12.331

Although ∼1/2 of adult patients (pts) with acute lymphoblastic leukemia (ALL) achieve long-term survival, those who relapse have poor long-term outcomes. The initial report of Phase (P) 1 of ZUMA-3, the P1/2 trial of KTE-X19 for treatment of relapsed/refractory (R/R) ALL (NCT02614066), demonstrated a 71% complete remission (CR) rate (CR or CR with incomplete hematologic recovery [CRi]), 88% undetectable minimal residual disease (MRD), and manageable toxicity (Shah et al. ASH 2017. #888). Here, we present updated ZUMA-3 P1 safety and efficacy data. Adult pts (≥ 18 y) with R/R ALL (Ph+ allowed), > 5% bone marrow (BM) blasts, and ECOG 0-1 received 2, 1, or 0.5 × 106 CAR T cells/kg after low-dose conditioning chemotherapy. The primary endpoint for P1 was incidence of dose-limiting toxicities (DLTs). Key secondary endpoints included incidence and time to onset and resolution of adverse events (AEs), rate of undetectable MRD remission in the BM, and duration of remission. Safety analyses included all pts who received KTE-X19; pts with ≥ 2 months of follow-up were evaluated for efficacy. As of April 12, 2018, 35 pts have received KTE-X19 (median follow-up of 11 months [range, 2 −25 months]). Median age was 40 years (range, 18 – 69 years), 51% male, 66% ECOG 1, 37% prior blinatumomab, and 60% ≥ 3 prior lines of treatment. Median BM blast burden at Screening was 70% (range, 5 −100). Six, 14, and 15 pts received 2, 1, and 0.5 × 106 cells/kg doses, respectively. No DLTs were observed in the DLT period. The most common Grade ≥ 3 AEs were hypotension (40%) pyrexia (34%), decreased platelet counts (34%), and anemia (31%). Grade ≥ 3 cytokine release syndrome (CRS) occurred in 9 pts (26%, median time to onset 5 days [range, 1 −15 days]); events resolved in all pts (excluding 2 with a Grade 5 event), and the median time to resolution was 11 days (range, 7 −42 days). There were 2 KTE-X19-related Grade 5 events: 1 cerebral infarction at the 0.5 × 106 cells/kg dose and 1 previously reported multiorgan failure secondary to CRS at the 2 × 106 cells/kg dose. Grade ≥ 3 neurologic events occurred in 16 pts (46%, median time to onset 7 days [range, 4 −24 days]); neurologic events resolved in all pts (excluding 2 patients with unresolved events at death), with a median time to resolution of 17 days (range, 6 −53 days). Among the 32 pts evaluable for response, the overall rate of undetectable MRD was 78% (95% CI, 60%–91%).CR or CRi was achieved by 23 pts (72%), and 1 pt (3%) had blas