ASH 2014: Oral Inhibitor Shows Clinical Activity in Poor-Prognosis AML


Key Points

  • The overall response rate was 19%; two patients had a complete response, and four had complete responses with incomplete blood count recovery.
  • Six of the 32 patients had at least a 50% reduction in bone marrow blasts.
  • Patients with IDH mutations may be particularly sensitive to ABT-199.

An oral targeted drug has shown encouraging activity and tolerable side effects in patients with treatment-resistant or relapsed acute myelogenous leukemia (AML), a poor-prognosis group with few options, reported investigators from Dana-Farber Cancer Institute and The University of Texas MD Anderson Cancer Center at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 118).

Of 32 patients treated with the oral inhibitor ABT-199, five had eradication of their leukemia and several more had stable disease, according to Anthony Letai, MD, PhD, of Dana-Farber, senior author of the report.

Phase II Trial

The phase II multicenter trial was the first use of ABT-199 in patients with relapsed or resistant AML. These patients often have received many previous treatments with chemotherapy or hypomethylating agents and are too debilitated to undergo aggressive therapies such as more intense chemotherapy or stem cell transplants.

The trial, involving 32 patients, was launched on the basis of preclinical studies from the laboratories of Dr. Letai and Marina Konopleva, MD, PhD, at Dana-Farber Cancer Institute and MD Anderson Cancer Center showing that ABT-199 could kill AML cell lines, patient AML cells, and patient-derived AML cells implanted into mice. ABT-199 targets the cancer “survival” protein BCL-2, which has been linked to resistance and poor prognosis in patients with AML.

Patients in the open-label trial ranged in age from 19 to 84 years, and the median age was 71.

The overall response rate was 19% (six patients), with two patients having a complete response. At the first assessment 4 weeks after treatment, one patient had a complete response (a second complete response was reported in the final results presented at ASH); four patients had complete responses with incomplete blood count recovery; one of the four achieved a complete response by week 20, the investigators reported. Six of the 32 patients had at least a 50% reduction in bone marrow blasts.

IDH mutations were found in three patients who achieved complete response or complete response with incomplete blood count recovery, and two of these patients also achieved minimal residual disease negativity.

No patients died as a result of adverse events from the treatment.

Next Steps

The researchers concluded that ABT-199 as a single agent “has considerable clinical activity in patients with poor-prognosis relapsed or resistant AML, and that patients with mutations in IDH genes may be particularly sensitive” to the drug.

Dr. Letai noted that that dose-limiting toxicity was not reached, leaving open the possibility of higher doses in further trials. The next step, he said, is to carry out trials combining ABT-199 with other agents. These trials are currently opening at several sites, including Dana-Farber.

The study was funded by AbbVie, Inc. For full disclosures of the study authors, view the study abstract.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.