S225: allogeneic stem cell transplantation for nk/t-cell lymphoma in the era of asparaginase-based chemotherapy: a retrospective analysis of the ebmt lymphoma working party

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Natural killer/T-cell lymphomas (NKTCL) represent rare and aggressive lymphoid malignancies. For patients (pts) with advanced stages III/IV and/or relapsed/refractory (r/r) disease guidelines recommend Asparaginase (ASPA)-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). These recommendations, however, are mostly based on small series of patients partly reported decades ago. Aims: To better define the role of allo-HSCT for patients with r/r NKTCL in the era of ASPA-based regimens. Methods: We conducted a retrospective analysis of EBMT registry and data from registries of cooperating centers in China and South Korea. The following inclusion criteria were applied: confirmed NKTCL, age ≥18 years, first allo-HSCT between 2010 and 2020, previous autologous HSCT allowed, peripheral blood or bone marrow as stem cell source. Outcome data were calculated from the day of allo-HSCT until the respective event. Results: We identified 135 pts who received allo-HSCT between 2010-2020. Median age was 43.4 years at the time of HSCT, 68.1% were male. Ninety-seven pts (71.9 %) were European, 38 pts (28.1%) were of Asian origin. High Prognostic Index for NKTCL (PINK) scores were reported for 44.4%; 76.3% had >1 treatment, 20.7% had a previous auto-HSCT, and 74.1% received ASPA-containing regimens prior to allo-HSCT. PD-1/PD-L1 inhibitor treatment was applied in 13 pts (9.6%) before and in 5 pts (3.7%) after allo-HSCT. Most (79.3%) pts were transplanted in CR/PR. Reduced-intensity conditioning (RIC) and myeloablative conditioning (MAC) were applied in 46.7% and 53.3% of cases, respectively. Most pts (91.1%) received peripheral blood stem cells. Main donor types were unrelated (43.7%), matched-related (35.6%) and haplo-identical (20%). With a median follow-up of 4.8 years, 3-year progression-free (PFS) and overall survival (OS) were 48.6% (95% CI:39.5-57%) and 55.6% (95% CI:46.5-63.8%), respectively. Non-relapse mortality (NRM) at 1 year reached 14.8% (95% CI:9.3-21.5%) and 1-year relapse incidence (RI) 29.6% (95% CI:21.9- 37.6%). RI at 3 years was 34.1% (95% CI:25.8- 42.4%), while no relapse was noted beyond 3 years after HSCT. In univariate analyses, there were no significant differences in outcomes regarding geographical region, conditioning intensity, donor type (including haplo-identical donors), prior PD-1/PD-L1 treatment and PINK score. In multivariate analyses, shorter time interval (<12 months) between diagnosis and allo-HSCT [HR=2.12 (95% CI:1.03-4.34); P=0.04] and transplantation not in CR/PR [HR=2.20 (95% CI:0.98-4.95); P=0.056] reduced PFS. Programmed cell death protein 1(PD-1/PD-L1) treatment before HSCT neither increased acute or chronic GVHD nor impacted on survival. Summary/Conclusion: We demonstrate that HSCT is an effective treatment approach for r/r NKTCL with almost half of the pts achieving long-term survival. These results were obtained with the majority of pts having been treated with state-of-the-art ASP-containing therapy prior to transplant compare favorably to previous analyses and show that HSCT is the preferred option for younger pts with ENKTL. PD-1 antibodies given prior to HSCT may help to bring more pts to HSCT without negatively influencing treatment outcomes or GvHD. Keywords: Allogeneic stem cell transplant, Allogeneic hematopoietic stem cell transplant, NK-T cells, Non-Hodgkin’s lymphoma