Autologous Hematopoietic Stem Cell Transplantation in Natural Killer/T-Cell Lymphoma: A Retrospective Analysis of the EBMT Lymphoma Working Party

Introduction NKTCL is a rare entity belonging to the peripheral T-cell lymphomas. For patients (pts) failing first-line therapy, current NCCN- and ESMO/EHA guidelines recommend transplantation as one option; however, both guidelines state that no clear data favoring allogeneic (alloHCT) or autologous transplantation (autoHCT) do exist. After reporting the largest series of pts undergoing alloHCT (Berning et al., Leukemia. 2023;37(7):1511-1520) this EBMT-registry-based study aims to investigate outcomes of NKTCL patients treated with autoHCT in the current treatment landscape. Methods We conducted a retrospective analysis of EBMT registry data and data from registries of cooperating Asian centers in China and South Korea. The following inclusion criteria were applied: patients with confirmed NKTCL, age ≥18 years, first autoHCT between 2011 and 2022, subsequent alloHCT allowed. Outcome data were calculated from the day of HCT until the respective event. Results The study included 130 patients (66.9% male) with a median age of 51.3 years (range 23-72.8) at HCT. Forty-three (33.1%) pts were reported from Asian centers, 87 (66.9%) pts from European centers. Median follow-up was 4.6 years. Advanced disease stage and high Prognostic Index for NKTCL (PINK) scores were reported in 65.3% and 23.9% of cases, respectively. EBV serology was positive in 65.7%, and EBV DNA was detectable in 82.9% of tested patients. Consolidative autoHCT after one treatment line was performed in 53.1% of cases, while 31.2% and 15.6% of pts had 2 or more prior treatment lines, respectively. Among the cohort, 16 patients (12.4%) were refractory at the time of HCT, including 4 who had one prior treatment line and 12 who had 2 or more. Asparaginase (ASP)-containing regimens were used in 79.5% of pts prior to HCT (66.2% in first line). PD-(L)1 inhibitors were applied in 17 pts (13.1%) prior to HCT. At HCT, 59.7% were in CR, 27.9% in PR, and 12.4% were chemorefractory/progressing. EBV copies were detectable at HCT in 37.3% of tested patients. The 1-year and 3-year PFS rates were 56.5% and 47.6%, while OS rates were 74.7% and 63.8%, respectively. The 1-year and 3-year relapse incidences (RI) were 37.7% and 46.7%, with a 1-year NRM of 5.7%. No significant difference was observed in outcomes between patients who underwent autoHCT after 1 treatment line and those who had 2 or more treatment lines prior to autoHCT. For patients with upfront autoHCT, the 1-year and 3-year PFS rates were 59.6% and 47.9%, respectively, while OS rates were 77.5% and 66.7%. In comparison, for patients with 2 or more lines, the 3-year PFS and OS were 45.5% and 59.4%, respectively. AlloHCT was performed in 13 patients (10.0%) following relapse after autoHCT. Univariate analyses showed no significant differences in PFS, OS, and RI regarding NKTCL manifestations (nasal vs. extranasal), ASP-based first-line treatment (ASP-based vs. non-ASP-based), or prior PD-(L)1-directed treatment. CR compared to non-CR at HCT was associated with improved OS (p=0.007), whereas advanced disease stage (III/IV) vs. limited (I/II) at diagnosis with reduced OS and PFS (both p<0.05). In multivariate analysis, accounting for year of HCT, age, disease status, and number of pretreatments, stage III/IV vs. I/II at diagnosis remained associated with reduced OS (HR=2.99, 95% CI: 1.37-6.50, p=0.006), while non-detectable EBV viral load at HCT significantly improved OS (HR=0.32, 95% CI: 0.16-0.62, p=0.001) and PFS (HR=0.43, 95% CI: 0.24-0.79, p=0.007). Conclusions In a large cohort of pts with state-of-the-art ASP-containing therapy our results show survival rates of approximately 50% after autoHCT. Results were comparable after one or more than one treatment line. Advanced disease stage at diagnosis and in particular detectable EBV viral load at autoHCT were identified as risk factors for poor outcomes. These data demonstrate that autoHCT is a valuable treatment option for pts with NKTCL, while alloHCT may remain an option for relapse after autoHCT.