Tocilizumab in combination with a standard induction chemotherapy in acute myeloid leukaemia patients (TOCILAM study): a single-centre, single-arm, phase 1 trial.

Background: In acute myeloid leukaemia (AML), interleukin-6 (IL-6) promotes chemo-resistance and its levels correlate with poor prognosis. IL-6 blockade may represent a promising therapeutic strategy. We aimed to test, tocilizumab, an anti-IL-6 receptor (R) monoclonal antibody in combination with standard intensive AML induction chemotherapy. Methods: This investigator-initiated single-centre phase 1 trial was conducted at Nantes University Hospital in France. According to a continual reassessment method, three escalating doses were tested of intravenous (IV) tocilizumab (4, 6, and 8 mg/kg) administered at day (d) 8 of a standard AML induction chemotherapy (IV idarubicine 8 mg/m Findings: Between Dec 29, 2020 and Dec 1, 2022, 12 patients were enrolled, of whom 75% had an ELN-2017 high-risk profile, and were treated with tocilizumab- two patients at 4 mg/kg, two at 6 mg/kg and eight at 8 mg/kg of tocilizumab. No dose-limiting toxicity related to tocilizumab was documented. There were nine serious adverse events, none of which were related to tocilizumab, and there was no treatment-related deaths. MTD was thus not reached. Two deaths occurred during induction. In the remaining ten evaluable patients, nine responded to treatment. Interpretation: The combination of tocilizumab with standard AML intensive induction appears to be safe and resulting responses are encouraging. A dose of 8 mg/kg of tocilizumab given at day 8 of induction could be used for further phase 2/3 studies. Funding: The Leucémie Espoir Atlantique Famille (LEAF)-"Tous avec Fabien" association.