Upfront allo-HSCT after intensive chemotherapy for untreated aggressive ATL: A single arm, phase 3 trial, JCOG0907

This single-arm, phase 3 trial by the Japan Clinical Oncology Group evaluated the strategy of upfront allogeneic hematopoietic stem cell transplantation (allo-HSCT) after intensive chemotherapy for untreated aggressive adult T-cell leukemia-lymphoma (ATL). Patients ≤ 65 years old with aggressive ATL were eligible. The protocol-treatment was VCAP-AMP-VECP as induction-chemotherapy followed by allo-HSCT in first remission. Between 2010 and 2020, 110 patients were enrolled. Among all 92 transplantations, 41 under per-protocol (study transplantation) and 51 under off-protocol received allo-HSCT. The primary endpoint was met with 3-year OS of 44.0% (90% CI, 36.0–51.6 > 25.0). The median survival time of the study transplantation and all transplantation was 3.0 (95% CI, 1.5–5.8) and 2.5 years (95% CI, 1.4–4.8), respectively. Multivariable analysis with a time-dependent covariate for transplantation revealed that the hazard ratio for OS of study transplantation was 0.915 (95% CI, 0.554–1.512). In study transplantation, the rate of treatment-related death (TRD) in related and unrelated transplantation was 16.7% and 20.7%, respectively. Thirty-four deaths due to disease progression (PD) were observed. Upfront allo-HSCT can be recommended for aggressive ATL despite a relatively high rate of PD and TRD. However, the survival benefit of study transplantation remains unclear considering the immortal bias.