A biological agent used without chemotherapy appears to offer a disease-free future to patients with rare leukemia

A biological agent — a drug that wraps vitamin A inside bubbles of fat — used without chemotherapy appears to offer as many as one-third of patients with a rare form of leukemia an opportunity for a long-term, disease-free future, say researchers at The University of Texas M. D. Anderson Cancer Center.

Researchers say the findings, presented at the annual meeting of the American Society of Clinical Oncology, provide the proof that biologic drugs can work in patients with acute promyelocytic leukemia (APL), and opens the door to development of such agents for more common forms of leukemia. 

“This is the first time we have seen patients with an acute leukemia potentially cured without use of chemotherapy,” says the study principal investigator, Elihu Estey, M.D., a professor in the Department of Leukemia. “That’s an important development in the field of leukemia, because traditional treatment with chemotherapy often produces side effects, even death, in patients with different kinds of leukemia than the one studied here.”

The researcher presenting the results at ASCO is Apostolia Maria Tsimberidou, M.D., Ph.D., an instructor in the Department of Leukemia.

In the small trial, approximately one-third of patients were found to be disease free for more than five years using the drug, Lipo-ATRA.

Lipo-ATRA is a lipidized form of the drug ATRA (all-trans retinoic acid), which was originally studied in China in patients with APL. ATRA is a form of vitamin A that was found to help patients diagnosed with APL, a malignancy of the bone marrow in which a genetic translocation leads to production of an excess of immature cells. The vitamin A derivative helps push the cells to mature.

Traditional treatment of APL combines ATRA, taken by mouth, with the chemotherapy drug, idarubicin. But realizing that little of the vitamin A is absorbed when swallowed, M. D. Anderson researchers worked to encase ATRA inside bubbles of fat.

“When you put ATRA in a lipid carrier and inject it, it is not metabolized and stays longer in tissues,” says a researcher who helped develop the treatment, Gabriel Lopez-Berestein, M.D., a professor in the Department of Experimental Therapeutics.

In the Phase II clinical trial being reported, patients received Lipo-ATRA for three months and then continued to receive the drug without chemotherapy as long as their bone marrow showed no evidence of the characteristic molecular signature of APL. If this marker was found, chemotherapy was added.

Of the 34 patients who received Lipo-ATRA, ten remain in remission for an average of five years, despite never receiving chemotherapy. Many of the patients who needed to receive chemotherapy also remain in remission “such that the overall proportion of patients cured approximates that seen with oral ATRA plus chemotherapy, with, however, fewer patients receiving chemotherapy,” says Estey.