Akt Inhibition With MK-2206 in Relapsed/Refractory Chronic Lymphocytic Leukemia

Akt inhibition combined with chemotherapy may be an effective strategy for patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to a study published in the American Journal of Hematology.¹

The activation of Akt — a downstream target of the B cell receptor — is associated with malignant cell survival and resistance to chemotherapy. For this phase 1/2 study (ClinicalTrials.gov Identifier: NCT01369849), researchers evaluated whether Akt inhibition via an investigational drug, MK-2206, would improve patient responses when used with chemotherapy.

The phase 1 part of the study, which included 6 patients, determined a maximum MK-2206 dose of 90 mg orally once per week when combined with bendamustine and rituximab (BR).

In phase 2, which included 13 patients with relapsed or refractory disease, patients received the maximum tolerated dose plus BR. The overall response rate was 92%; median progression-free survival was 16 months.

Common grade 3/4 adverse events included neutropenia, febrile neutropenia, rash, diarrhea, and thrombocytopenia.

The authors concluded that Akt inhibition with BR is a promising strategy for patients in the relapsed/refractory setting. The results “at least compare similarly to” previous efficacy data of BR in relapsed CLL.

Reference

1. Larsen JT, Shanafelt TD, Leis JF, et al. Akt inhibitor MK-2206 in combination with bendamustine and rituximab in relapsed or refractory chronic lymphocytic leukemia: results from the N1087 Alliance Study. Am J Hematol. In press.