Flotetuzumab as a salvage immunotherapy in advanced CD123-positive hematological malignancies, a phase 1 pilot study

Abstract

CD123 “expression” is common in hematological malignancies, including acute lymphoblastic leukemia (ALL). Flotetuzumab is a novel, investigational CD3/CD123 DART®. We conducted a phase 1 study evaluating safety and efficacy of flotetuzumab in relapsed/refractory ALL (Cohort A) and other advanced CD123-positive hematological malignancies (excluding myeloid malignancies) (cohort B). Thirteen patients (9 in Cohort A and 4 in Cohort B) were treated at dose level 1 (500 ng/kg/day) before early closure due to discontinuation of drug development by sponsor. Two dose limiting toxicities (Grade 4 thrombocytopenia and neutropenia) occurred in one patient in Cohort B. Cytokine release syndrome occurred in most patients (85%), all being grade ≤2. Responses only occurred in Cohort B, with a partial response in one patient with Hodgkin’s lymphoma and morphological complete remission in the bone marrow in one patient with blastic plasmacytoid dendritic cell neoplasm. In conclusion, flotetuzumab had a manageable safety profile in advanced CD123-positive hematological malignancies.

Keywords:

• Flotetuzumab
• immunotherapy
• CD123
• lymphoma
• ALL

Acknowledgments

We would like to acknowledge the dedication and support of the medical, nursing, and administrative staff of City of Hope. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Macrogenics. We thank our patients and volunteers for supporting research through their participation in our Hematological Tissue Biorepository protocols. This work was financially supported by Macrogenics. Research reported in this publication included work performed by the Research Pathology and the Biostatistics and Mathematical Oncology shared resources supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure statement

I.A. received research support from MacroGenics and Abbvie, and served on Advisory Board for Amgen, Pfizer, KiTE, JAZZ, Takeda, Syndax, and Wugen. The remaining authors report there are no competing interests to declare.

Data availability statement

Data availability can be provided upon request the corresponding author.