Tapotoclax Is Safe after HMA Failure in MDS

By Patrick Daly - Last Updated: December 5, 2024

The myeloid cell leukemia 1 (MCL1) inhibitor tapotoclax was safe in patients with myelodysplastic syndromes (MDS) after hypomethylating agent (HMA) failure, according to findings presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

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“This phase I study demonstrated that tapotoclax was safe and tolerated in a high-risk cohort of patients with HMA failure MDS,” said the study’s lead author, Kelly Chien, MD, of the University of Texas MD Anderson Cancer Center. “No dose-limiting toxicities were observed, and cardiac adverse events self-resolved without dose reductions.”

Phase I Trial on Tapotoclax Safety, Tolerability

The trial included four patients who received tapotoclax 120 mg/m2 and three who received tapotoclax 240 mg/m2. The most common treatment-related adverse events (AEs) were nausea (85%), fatigue (57%), diarrhea (29%), and palpitations (14%). One patient experienced arrhythmias potentially related to tapotoclax, but they self-resolved, according to the authors. No clinically significant elevations in troponin were reported.

No patients experienced a response. Four discontinued due to lack of response, one underwent allogeneic stem cell transplantation, one discontinued due to recurrent peritoneal cancer, and one discontinued by request with subsequent, unrelated death.

However, two of three patients with bone marrow blasts of 5% or more at initiation had unsustained blast reduction after cycle three. Additionally, five patients reduced their red blood cell transfusion burden by two or more units from cycle one to cycle two, and one patient achieved transfusion independence for seven weeks.

“Given its manageable toxicity profile and transient antileukemic and transfusion-independent effect, the use of tapotoclax in combination with HMA or other therapies may warrant further consideration,” Dr. Chien and colleagues concluded.

Reference

Chien K, Rodriguez-Sevilla JJ, Alvarado Y, et al. A phase I study of the myeloid cell leukemia 1 (MCL1) inhibitor tapotoclax (AMG 176) in patients with myelodysplastic syndromes after hypomethylating agent (HMA) failure. Abstract #MDS-537. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.

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