Improved survival after post-transplant relapse of adult t-cell leukemia-lymphoma and trends of salvage therapy Free

Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potentially curative outcomes for adult T-cell leukemia-lymphoma (ATL), but post-transplant relapse still occurs in approximately 30-40% of patients. Recent advances in novel agents have expanded therapeutic options, and improvements in supportive care may have contributed to better post-transplant management. However, it remains unclear whether outcomes after post-transplant relapse or refractory (R/R) ATL have improved in recent years. We here investigated survival trends following post-transplant relapse or refractory in unselected patients.

Methods This study included patients who (i) received their first allo-HSCT between 1999 and 2022 and (ii) developed R/R ATL after allo-HSCT. In a total, 549 patients did not achieve complete remission after allo-HSCT (the Refractory group), and 597 patients achieved remission but subsequently experienced relapse (the Relapse group). Clinical data were collected from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation. To evaluate the impact of time period on outcomes, overall survival (OS) after refractory or relapse was analyzed using Cox proportional hazards regression models.

Results Among a total of 1146 patients with post-transplant R/R ATL, 406 (Refractory: n=192, Relapse: n=214), 426 (Refractory: n=213, Relapse: n=213), and 314 (Refractory: n=144, Relapse: n=170) patients received their first allo-HSCT in 1999-2010 (early period), 2011-2016 (middle period), and 2017-2022 (late period), respectively. Over these periods, significant increases were observed in the proportion of patients aged 60 years or older (P<0.001), better performance status (PS)(P<0.001), lower hematopoietic cell transplantation-comorbidity index (HCT-CI)(P<0.001), and the greater use of reduced-intensity conditioning (RIC) regimen (P=0.006). The use of unrelated cord blood grafts increased from 25.1% in the early period to 36.2% in the middle period and 38.5% in the late period. The use of grafts from HLA-haploidentical related donors remained low in the early (6.4%) and middle periods (5.4%), respectively, but increased markedly to 20.1% in the late period.

Regarding salvage therapy for post-transplant R/R ATL, while mogamulizumab (Mog) or lenalidomide (Len) was used in less than 3% of patients during the early and middle periods, the utilization of these agents increased in the late period: Mog (20.8%) and Len (11.8%) in the Refractory group; and Mog (27.6%) and Len (21.2%) in the Relapse group. The use of donor lymphocyte infusion-based therapy significantly decreased over the three periods: the early (8.3%), middle (3.8%), and late periods (3.5%) in the Refractory group; and the early (15.0%), middle (8.5%), and late periods (4.1%) in the Relapse group.

In the Refractory group, the 1-year unadjusted overall survival (OS) rates were 8.8%, 9.6%, and 17.1% in the early, middle, and late periods, respectively (P<0.001). Multivariate analysis showed no significant difference in OS between the early and middle periods (hazard ratio [HR], 1.01 [95% confidence interval, 0.80-1.28]; P=0.923), but demonstrated better OS in the late period than the early period (HR 0.72 [0.55-0.95]; P=0.018). The 1-year adjusted OS rates were 8.6%, 7.5%, and 14.1% in the early, middle, and late periods, respectively.

In the Relapse group, the 1-year unadjusted OS rates were 25.9%, 37.2%, and 36.7% in the early, middle, and late periods, respectively (P=0.002). Multivariate analysis showed improved OS in the middle (HR 0.62 [0.48-0.80]; P<0.001) and late periods (HR 0.68 [0.52-0.90]; P=0.007) compared to the early period. No significant difference in OS was seen between the middle and late periods. The 1-year adjusted OS rates were 25.4%, 37.7%, and 38.7% in the early, middle, and late periods, respectively.

Conclusion This study demonstrated a trend toward improvement in the late period for the Refractory group, and in both the middle and late periods for the Relapse group. We observed significant increases in (i) the use of RIC regimen and (ii) patients with better HCT-CI and PS at allo-HSCT, which may have expanded the population eligible for salvage therapy due to improved tolerability. Furthermore, it is important to note that the introduction of Mog and Len would contribute to improved survival of patients with the post-transplant R/R ATL in the late period.