Exploration of Efficacy and Safety of Adjunctive Methylene Blue in the Treatment of Immunotherapy-related CRS and ICANS: A Prospective, Single-arm, Phase I Clinical Study
This Phase I, prospective, single-arm clinical study aims to evaluate the efficacy and safety of adjunctive methylene blue (MB) in patients experiencing cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) following CAR-T cell therapy or bispecific antibody treatment. Preclinical studies demonstrated that MB alleviates CRS/ICANS-related symptoms, preserves the antitumor function of T cells, and modulates neuroinflammation without compromising immune efficacy. The study will employ a 3+3 dose-escalation design with three MB dosing cohorts, with treatment administered intravenously for 3-5 consecutive days. Vital signs, laboratory markers, and neurological status will be closely monitored, and concomitant standard supportive therapies will be permitted.
• Diagnosed with hematologic malignancies based on cytomorphology and immunophenotyping; age ≥18 years.
• Received immunotherapy (e.g., CAR-T cells, bispecific antibodies) and developed CRS or ICANS of ASTCT Grade ≥1.
• Estimated life expectancy ≥3 months.
• Male and female participants of childbearing potential agree to use effective contraception.
• Left ventricular ejection fraction (LVEF) \>45% by echocardiography.
• Ability to understand and sign informed consent and willingness to comply with study requirements.