KITE-222 Shows Manageable Safety but Limited Activity in Relapsed or Refractory Acute Myeloid Leukemia

Clinical Summary:

• Design/Population: In a phase 1 dose-escalation trial, 12 patients with relapsed/refractory acute myeloid leukemia received KITE-222, an autologous CAR T-cell therapy targeting CLL-1.
• Key Outcomes: KITE-222 demonstrated acceptable safety with limited severe cytokine release syndrome or neurotoxicity; however, clinically meaningful remissions were not observed despite evidence of CAR T-cell expansion and depletion of CLL-1–positive blasts in some patients.
• Clinical Relevance: These findings highlight ongoing challenges with CAR T-cell therapy in AML and support further development of strategies to overcome antigen heterogeneity and improve antitumor activity.

Results from a phase 1 dose-escalation trial demonstrated that KITE-222, an autologous CLL-1-directed CAR T-cell therapy, demonstrated limited clinical efficacy but tolerable safety among patients with relapsed or refractory acute myeloid leukemia (AML).

“CAR T-cell therapy has been a breakthrough in many hematologic malignancies, but success in relapsed/refractory AML has been limited due to underwhelming response rates and high on-target/off-tumor toxicity,” stated Naval Daver, MD, MD Anderson Cancer Center, Houston, Texas, and coauthors. This study “evaluated the safety and efficacy of KITE-222… predominantly expressed on myeloid cells but absent on normal hematopoietic stem cells and other tissues.” 

In this open-label trial, 12 adult patients received a single infusion of KITE-222 at escalating dose levels of 3 × 10⁷ (n = 3), 1 × 10⁸ (n = 3), or 3 × 10⁸ (n = 6) CAR-positive T cells. The primary end point was incidence of dose-limiting toxicities. Key secondary end points included remission rate, incidence of adverse events, and pharmacokinetic and pharmacodynamic outcomes.

At analysis, 1 dose-limiting toxicity consisting of prolonged grade 4 neutropenia followed by grade 4 thrombocytopenia was reported in cohort 3 after a second course of lymphodepleting chemotherapy. This patient achieved a morphologic leukemia-free state that was confirmed on day 44 after infusion. All enrolled patients experienced grade ≥3 adverse events. No grade ≥3 cytokine release syndrome was reported, and 1 case of grade ≥3 immune effector cell–associated neurotoxicity syndrome occurred.

Among 5 patients in cohort 3 with evidence of CAR T-cell expansion, 2 experienced near-complete depletion of CLL-1-positive bone marrow blasts; however, CLL-1-negative blasts persisted, and reductions in total blast burden were not observed. Despite detectable CAR T-cell expansion across dose levels, clinically meaningful responses were not observed, and the trial was terminated before initiation of the expansion phase.

These results warrant “future studies that address CLL-1 heterogeneity and focus on improving in vivo expansion and antitumor activity," concluded Dr Daver et al. 

Source: 

Daver N, Blachly JS, Ghobadi A, et al. Phase 1 study of KITE-222, an autologous CLL-1–directed CAR T-cell therapy in patients with relapsed/refractory acute myeloid leukemia. Clin Can Res. Published online: June 4, 2026. doi:10.1158/1078-0432.CCR-25-374