The development of CLL and other hematologic malignancies is often associated with the dysfunction of certain proteins that regulate cell death (apoptosis), known as B-cell lymphoma-2 (BCL-2) proteins, which allow cancerous cells to live longer and replicate in the body.

Using these proteins as a treatment target, researchers have developed a novel compound, ABT-199, that may be able to help trigger cell death in these tumours.

To determine the maximum tolerated dose of ABT-199, researchers have enrolled 56 patients with relapsed or treatment-resistant CLL or small lymphocytic lymphoma in an ongoing Phase I study. Patients are divided into several cohorts to receive different doses of the drug (ranging from 150 to 1200 mg).

The preliminary study results show encouraging drug activity, as evidenced by an 84 percent overall response rate and a 21 percent complete response rate in the study population. Early in the treatment period, some patients experienced tumour lysis syndrome (TLS), a treatment toxicity that occurs when contents of tumour cells that have been rapidly destroyed by effective therapy are released into the blood, potentially causing organ damage.

Investigators therefore reduced the initial dose and instituted a progressive, slow increase in dose over the first several weeks of ABT-199 treatment, which helped to prevent and control TLS during the remainder of the treatment period.

“We are very encouraged by these early results and in particular, by the high rate of complete response among patients with treatment-resistant or relapsed CLL,” said John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia.

“Our ongoing work will seek to improve the efficacy of this drug while carefully monitoring toxicities to deliver the maximum benefit to high-risk patients where conventional chemotherapy has proven inadequate.”

Source: ASH