TREATMENT WITH A NEW SYNTHETIC RETINOID, AM80, OF ACUTE PROMYELOCYTICLEUKEMIA RELAPSED FROM COMPLETE REMISSION INDUCED BY ALL-TRANS-RETINOIC ACID

Differentiation therapy with all-trans retinoic acid (ATRA) has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). However, patients who relapse from ATRA-induced complete remission (CR) have difficulty in obtaining a s econd CR with a second course of ATRA therapy alone. We tested the eff icacy of a new synthetic retinoid, Am80, in APL that had relapsed from CR induced by ATRA in a prospective multicenter study. Am80 is approx imately 10 times more potent than ATRA as an in vitro differentiation inducer, is more stable to light, heat, and oxidation than ATRA, has a low affinity for cellular retinoic acid binding protein, and does not bind to retinoic acid receptor-gamma, Patients received Am80, 6 mg/m( 2), orally alone daily until CR. Of 24 evaluable patients, 14 (58%) ac hieved CR. The interval from the last ATRA therapy was not different b etween CR and failure cases. The clinical response was well correlated with the in vitro response to Am80 in patients examined. Adverse even ts included 1 retinoic acid syndrome, 1 hyperleukocytosis, 9 xerosis, 8 cheilitis, 16 hypertriglyceridemia, and 15 hypercholesterolemia, but generally milder than those of ATRA, which all patients had received previously. Am80 is effective in APL relapsed from ATRA-induced CR and deserves further trials, especially in combination with chemotherapy. (C) 1997 by The American Society of Hematology.