Leukaemia - tamibarotene

Patients with acute promyelocytic leukaemia experience a deficiency in mature red blood cells and an excess of immature cells within the bone marrow and peripheral blood. It is invariably associated with a translocation between chromosomes 15 and 17; the resulting PML retinoic acid receptor a fusion gene produces a chimeric protein that prevents myeloid cells maturing at the promyelocytic stage.

Current treatment options include arsenic trioxide and all-trans retinoic acid (ATRA), either alone or alongside chemotherapy, but resistance to ATRA often develops rapidly. An alternative RARa agonist, tamibarotene, has been developed by Nippon Shinyaku, which should have a lower propensity to developing resistance.

In a Phase II study in patients who had relapsed after ATRA therapy, 12 were given 6mg/m2 per day of the drug orally, and six achieved a complete response.¹ Minimal toxicity was observed.

A further, multicentre, trial was carried out in patients who had relapsed from the complete response that had been induced by ATRA.² They were given 6mg/m² of the drug per day until they achieved a complete response; 14 of the 24 evaluable patients achieved a complete response again. Side-effects included hypercholesterolaemia and hypertriglyceridaemia, but on the whole these were milder than they had experienced with ATRA.

The long-term clinical outcome of those who achieved that second complete response have also been reported: four relapsed within six months despite chemotherapy, six had a bone marrow transplant, and four of the eight who did not were still alive with no relapse after four years.³ The drug has now been launched in Japan and shows great promise as a treatment for APL.