ALLOGENEIC STEM CELL TRANSPLANTATION for FOLLICULAR LYMPHOMA, A BENCHMARK STUDY from the EBMT LYMPHOMA WORKING PARTY

Abstract

Background: Follicular lymphoma is characterized by an indolent course. Chemoimmunotherapy induction and maintenance leads to prolonged progression-free survival (PFS) for the vast majority of patients. However, high risk patients experience early and frequent relapses despite available therapies. Allogeneic stem cell transplantation (allo) is a potentially curative option relying on an established graft versus lymphoma effect but associated with high non relapse mortality (NRM). Therapeutic advances in the field including the success of T-cell engaging therapies are challenging the role of allo in FL and numbers are decreasing. In this study we aim to benchmark the outcome of allo in a large contemporary cohort. Method(s): We performed a registry-based retrospective study on adult patients who received a first allo for FL between 2010 and 2022 in the absence of any history of aggressive transformation. Result(s): We identified 1744 patients meeting the inclusion criteria. Their characteristics are listed in Table 1. With a median follow-up of 5.5y (95% CI 5.2-5.9]), 5y overall survival (OS), PFS, relapse incidence (RI) and NRM were 58% (95% CI 55-61]), 51% (95%CI 48-53]), 20% (95% CI 18-22]) and 30% (95% CI 27-32]),respectively. The cumulative incidence of grade II-IV and III-IV acute GVHD at day 100 were 30% (95% CI 28-33]) and 12% (95% CI 10-13]) respectively. The 2y cumulative incidence of extensive chronic GVHD was 17% (95%CI 15-19]). At 5y, the GVHD-free, relapse-free survival (GFRFS) was 36% (95%CI 33-38], as shown in Figure 1. Separating the cohort in two equal periods we did not observe any difference in OS, PFS, RI or NRM over time. While acute GVHD incidence did not change over time, cumulative incidence of chronic GVHD was lower in the most recent period (2016-2022). The use of haploidentical donors and post-transplant cyclophosphamide (PTCy) increased from 7 and 11 to 14% and 24% respectively in the second time period. Focusing on transplant years 2016 to 2022, we performed a multivariate analysis on variables of interest. Older age was associated with inferior OS, PFS and GRFS and with significant higher risk of relapse and NRM, as well as severe acute and chronic GVHD. Patients in partial remission or refractory disease at transplant had inferior PFS and higher RI but similar OS as compared to patients in CR. More than 80% of the patients had received 3 lines or more of therapy and this was associated with a lower RI as compared with patients transplanted after less than 3 lines. The intensity of the conditioning, the use of TBI or ATG were not significantly associated with outcome in this cohort. Interestingly, a previous ASCT was associated with a shorter OS based on higher NRM. (Table present) (Figure present) Conclusion(s): Our study confirms the high efficacy of allogeneic stem cell transplantation in FL, at the cost of high non relapse mortality, even in the most recent years. While being challenged by the emergence of T-cell engaging therapies, allo remains a valid option, especially if T-cell engaging therapies are not available or in case of relapse after CAR T-cells or bispecific antibodies.