Outcome of Hematopoietic Stem Cell Transplantation for Follicular Lymphoma, a Benchmark Study from the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation

Follicular lymphoma (FL) is characterized by repeated relapses. Chemo-immunotherapy leads to durable response in most patients in need for treatment. However, a subset of patients presenting a more aggressive disease course or early relapses can be offered hematopoietic stem cell transplantation (HSCT) as a potentially curative option. The role of HSCT is currently challenged by the rise of T-cell engaging therapies such as bispecific antibodies and CAR-T cells. Despite promising results, the curative potential of these new modalities is not demonstrated yet. Here, we report the outcome of autologous (ASCT) and allogeneic (allo) HSCT for FL reported to the EBMT.

We selected adult patients who received a first HSCT for FL between 2010 and 2022. Patients with aggressive transformation were not included. Data were collected in the EBMT registry in conformity with the Declaration of Helsinki and local regulations. Race and ethnicity data were not available. Statistical analyses were performed as recently described (Devillier, Am J Hem 2024).

We report 7330 ASCT patients meeting the inclusion criteria. Median age was 57y (IQR [50-63]) with 58% male patients. Most of the patients had been exposed to rituximab (86%). Disease status at transplant by Lugano criteria was complete response (CR), partial response (PR) or refractory disease (stable disease SD, progressive disease PD) in 53%, 37% and 10% of patients respectively. The conditioning regimen was BEAM in 66% of the cases and 99% of patients received peripheral blood stem cells (PBSC). With a median follow-up (FU) of 3.2y (95% CI [3-3.3]), 3y overall survival (OS), progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM) were 81% (95% CI [80-82]), 55% (95% CI [53-56]), 41% (95% CI [39-42]) and 5% (95% CI [4-5.1]), respectively. At 10 years, OS was 58% (95% CI [56-61]) and PFS 37% (95% CI [35-38]).

We then analyzed 1901 allo-HSCT for FL in the inclusion period. The median age was 54y (IQR [47-60]) with 62% male patients. At transplant, 48% were in CR, 32% in PR and 20 % SD-PD and 53% had relapsed after a previous ASCT. A reduced intensity conditioning (RIC) was used for 72% of patients.

Total body irradiation (TBI) was part of the conditioning in 23 % of the cases. GVHD prophylaxis included campath in 23%, post-transplant cyclophosphamide (PTCy) in 12% and ATG in 33% of the patients. PBSC was the cell source in 93% of the cases, from matched unrelated donor (MUD, 57%), sibling (34%), or haploidentical (haplo 8%). With a median FU of 5.2y (95% CI [5-5.6]), 5y OS, PFS, RI and NRM were 59% (95% CI [56-61]), 51% (95% CI [48-54]), 20% (95% CI [18-22]) and 30% (95% CI [27-32]), respectively. The cumulative incidence (CI) of grade 2-4 and 3-4 acute graft versus host disease (aGVHD) at day 100 were 30% (95% CI [28-32]) and 12% (95% CI [10-13]), respectively. The CI of extensive chronic GVHD was 17% (95% CI [15-19]) at 2y. At 10y, OS, PFS and GVHD-free, relapse-free survival (GFRFS) were 51% (95% CI [48-54]), 44% (95% CI [41-47]) and 29% (95% CI [26-32]), respectively.

In multivariate analysis of allo-HSCT patients, OS was worse with increased age in RIC (5y intervals, HR=1.25, 95% CI [1.18-1.32],p <0.001) and myeloablative (MAC) recipients (HR=1.12, 95% CI [1.02-1.22], p=0.012). As compared with patients in CR, RIC patients in PR and SD-PD had worse OS (HR=1.23, 95%CI [1.00-1.51], p=0.045 and HR=1.31, 95%CI [1.03-1.67], p=0.027 respectively). In the MAC group, OS was worse when transplanted in PR (HR=1.45, 95%CI [1.02-2.06], p=0.036) or SD-PD (HR=1.52, 95%CI [1.04-2.21], p=0.029) than in CR. Among RIC but not MAC recipients, OS was better in patients who received a TBI-based conditioning (HR=0.68, 95% CI [0.53–0.88], p = 0.003) and worse for patients transplanted with a haplo (HR=2.29, 95% CI [1.58–3.31], p <0.001) or MUD (HR=1.42, 95% CI [1.16-1.75], p <0.001), as compared to matched sibling donors.

Our analysis confirms that ASCT and allo-HSCT lead to durable disease control in a selected subset of FL patients. These results may serve as a benchmark against which to compare the outcome of new therapies in this population.