Salvage-free, transplantation-free survival: a proposal for a new clinical endpoint in acute myeloid leukemia.

Abstract

Results from pivotal clinical trials evaluating the combination of intensive chemotherapy with targeted therapies in acute myeloid leukemia (AML) are expected soon. While overall survival (OS) or event-free survival (EFS) are the recommended endpoints, new criteria are needed for assessing the intrinsic effectiveness of new drugs. In this study, the salvage-free, transplantation-free survival (STFS) was measured from day 1 of induction chemotherapy to the date of induction failure or salvage therapy, allogeneic transplantation (allo-HSCT), relapse, or death from any cause, whichever occurs first and assessed in a cohort of 1966 AML patients from the DATAML registry treated with intensive chemotherapy and 100 acute promyelocytic leukemia (APL) patients treated with arsenic trioxide and all-trans retinoic acid. Validation cohorts from the ALFA group were used. At five years, STFS was estimated at 14.6% (95% confidence interval [CI], 13.0-16.2; median, 5.5 months) whereas OS, EFS and relapse-free survival estimations were 40.4% (95% CI, 38.2-42.6; median, 30.6 months), 31.4% (95% CI, 29.4-33.5; median, 15.3 months) and 37.6% (95% CI, 35.2-40.0; median, 21.9 months), respectively. Relapse was the most common first STFS event, followed by allo-HSCT. STFS varied depending on molecular subgroups and gene-gene mutation interactions. In the APL cohort, STFS (83.6% at five years) was similar to OS (85.6%) illustrating the impact of an effective and low-toxicity first-line treatment curing patients without salvage therapy or allo-HSCT. In the prospective randomized ALFA-0701 trial, gemtuzumab ozogamycin significantly improved STFS. STFS should complement other survival endpoints to accurately analyze the impact of new drugs in AML.