Expanding the therapeutic arsenal

From San Diego, at a meeting of the American Society of Hematology

Two experimental pills can send chronic myeloid leukemia into remission in some patients who don’t benefit from the best available medicine, early results from three studies show.

In many patients with this blood cancer, the genes encoding proteins called Bcr and Abl become fused. This genetic mutation results in a defective protein, Bcr-Abl, that causes runaway proliferation of white blood cells.

Researchers reported 5 years ago that the drug imatinib, also called Gleevec, disables the rogue Bcr-Abl protein and stops cell replication (SN: 12/11/99, p. 372). Imatinib halts the cancer in more than 80 percent of patients, says Moshe Talpaz of the M.D. Anderson Cancer Center in Houston. However, some patients acquire additional changes in Bcr-Abl, become resistant to imatinib’s effects, and relapse.

Previous research found that a new drug dubbed BMS-254825 stops such imatinib-resistant cancer in mice (SN: 7/17/04, p. 38: Available to subscribers at Leukemia Fighter: Drug could combat resistant cases). The drug is made by Bristol-Myers Squibb of New York.

Talpaz teamed with Charles L. Sawyers of the Howard Hughes Medical Institute at the University of California, Los Angeles in two trials to assess BMS-254825’s effects in people with leukemia that was either resistant to imatinib or had already progressed to late stages, in which imatinib is generally not effective.

In one trial, Sawyers reports, 31 of 36 imatinib-resistant patients in an early phase of leukemia saw their white blood counts return to normal after treatment with BMS-254825. In a second trial, the researchers gave BMS-254825 to 29 patients with more-advanced leukemia. Most made progress against the disease, Talpaz says, but he cautions that it is too early to know whether the drug will remain effective in such patients.

In a separate trial, another experimental drug called AMN107 reduced the number of cancerous cells in the blood and marrow of roughly half of 65 people with chronic myeloid leukemia, reports Francis E. Giles, also of M.D. Anderson. AMN107 and imatinib are made by Novartis Pharmaceuticals of East Hanover, N.J.