North American Intergroup: all-trans retinoic acid in acute promyelocytic leukaemia
This randomised trial showed that the vitamin A derivative retinoic acid, used in induction and as maintenance, sharply improved survival in acute promyelocytic leukaemia compared with chemotherapy alone.
Overview
Phase 3 trial of 346 patients with newly diagnosed APL randomised to induction with all-trans retinoic acid or with daunorubicin plus cytarabine, and then to maintenance retinoic acid or observation.
Three-year disease-free survival was 67 percent after retinoic acid induction against 32 percent after chemotherapy, and maintenance retinoic acid further reduced relapse. The trial established retinoic acid as essential to APL therapy.
- Three-year disease-free survival 67 percent with retinoic acid induction vs 32 percent with chemotherapy induction.
- Maintenance retinoic acid improved disease-free survival compared with observation.
Differentiation therapy, making leukaemic cells mature rather than killing them, became the first targeted treatment in leukaemia. Every modern APL regimen starts with retinoic acid on suspicion of the diagnosis.
- Retinoic acid syndrome caused deaths before steroid prophylaxis became routine.
- Modern regimens combine retinoic acid with arsenic trioxide, which was not available at the time.