The bispecific antibody flotetuzumab demonstrated promising activity and safety in patients with acute myeloid leukemia (AML) and primary induction failure (PIF) or early relapse (ER), according to recent findings from a clinical trial published in the journal Blood.

In this ongoing, open-label phase 1/2 trial ( Identifier: NCT02152956), patients with relapsed/refractory AML or intermediate-2/high-risk myelodysplastic syndrome were separated into 2 groups for treatment with flotetuzumab. One group was a dose-escalation group (42 patients), and the other group was assigned to the recommended phase 2 dose (RP2D) expansion phase (46 patients). Primary objectives of the study included determination of the maximum tolerated dose and treatment schedule, in addition to evaluation of dose-limiting toxicities.

The RP2D was 500 ng/kg/day, and 50 patients across treatment groups received this dose. Overall response rates (ORRs) were 13.6% for all patients in the study and 24% for patients receiving the RP2D. The median study follow-up for RP2D patients was 0.8 months (range, 0-25), with a median time-to-first-response of 0.84 months (range, 0.8-2.1).

Continue Reading

A total of 30 patients receiving the RP2D had AML with either PIF or ER (relapsing before 6 months), and these patients had an ORR of 30%. This included a rate of 26.7% for complete response (CR) or CR with partial hematological recovery, and this level of response was often seen with immune infiltration in the tumor microenvironment.

The researchers additionally estimated predictors of response. Using a classifier that was based on 10 genes that showed expression associated with CR, an analysis of a receiver operating characteristic curve gave an area under the curve of 0.854. This level of accuracy compared favorably to a score of 0.672 obtained when using the 2017 European LeukemiaNet (ELN) classifier. In an analysis that combined the 10-gene classifier with the ELN risk category, the area under the curve was 0.904.

Infusion-related reactions (IRRs)/cytokine release syndrome (CRS) of grades 1 or 2 constituted the most frequent adverse events, reported in 81.0% of the dose-escalation group and 96.0% of the RP2D group. Grade 3 or higher IRRs/CRS occurred in 7.1% of and 8.0% of each group, respectively. Techniques to limit severe IRRs/CRS included step-up lead-in dosing, temporary dose modifications, pretreatment dexamethasone, and treatment with tocilizumab.

“Flotetuzumab represents an innovative experimental approach that has demonstrated acceptable safety and encouraging evidence of activity,” the researchers concluded.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of authors’ disclosures.


Uy GL, Aldoss I, Foster MC, et al. Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia. Blood. 2021;137(6):751-762. doi: 10.1182/blood.2020007732