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).

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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.

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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.


  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.