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

Marginal zone lymphomas (MZL) are a heterogenous group of indolent B-cell non-Hodgkin lymphoma, usually characterized by a non-aggressive course with a long survival for the majority of the patients. When they are symptomatic, patients usually respond to immuno-chemotherapy. However, a small group of patients relapse early or are refractory to standard treatment. Autologous (ASCT) or allogeneic (allo) hematopoietic stem cell transplantation (HSCT) may then be indicated, but because of the rarity of the disease, data on the outcome of ASCT and HSCT are scarce and recent large prospective series are lacking. As new options such as small molecules and T-cell engaging therapies emerge, it is relevant to analyze the results of established therapies. Here we present the outcome of MZL patients after ASCT and allo-HSCT who were reported to the EBMT.

We selected adult patients who received a first ASCT or allo-HSCT for MZL 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 et al, Am J Hem 2024).

Between 2010 and 2022, 874 patients received ASCT for MZL. Median age was 58y (IQR [51-64]) with 55% male patients. Median time from diagnosis to ASCT was 34 months (IQR [16-64]). Disease status at transplant was complete response (CR), partial response (PR) or refractory disease (stable disease SD, progressive disease PD) in 53%, 36% and 11% of patients respectively. The conditioning regimen used was BEAM in 60% of the cases and virtually all patients received peripheral blood stem cells (PBSC). With a median follow-up of 3y (CI 95% [2.5-3.3], the 3y overall survival (OS), progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM) were 75% (CI 95% [71-78]), 54% (CI 95% [50-58]), 38% (CI 95% [33-42]), and 8% (CI 95% [6-11]), respectively. At 10 years, OS was 45% (CI 95% [37-54]) and PFS 28% (CI 95% [22-35]). In multivariate analysis, older age (5y-interval) was significantly associated with worse OS (HR 1.26, CI 95% [1.15-1.39], p<0.001), PFS (HR=1.1, CI 95% [1.02-1.18], p=0.01), and higher NRM (HR=1.28, CI 95% [1.08-1.52], p=0.004). As compared with patients in CR, patients with refractory disease had a worse OS (HR=1.67, CI 95% [1.1-2.54], p=0.017) and PFS (HR=2.05, CI 95% [1.45-2.91], p<0.001) and a higher relapse incidence (HR=2.18, CI 95% [1.47-3.22], p<0.001). For patients in PR, relapse incidence was significantly higher than for patients in CR (HR=1.35, CI 95% [1.02-1.80], p=0.039) at transplant whereas OS and PFS were not significantly different with respect to remission status at transplant.

We identified 169 adult patients who received an allo-HSCT for MZL in the inclusion period. Median age was 57y (IQR [50-63]) with 63% male patients. At the time of transplant, 48% of patients were in CR, 34% in PR and 18% had a SD or PD. Median time from diagnosis to allo-HSCT was 48 months (IQR [27-83]) and 46% of patients had relapsed after a previous ASCT. A reduced intensity conditioning (RIC) was used for 65% of patients. Total body irradiation was part of the conditioning in 23 % of the cases. Graft versus host disease (GVHD) prophylaxis included ATG in 40% and post-transplant cyclophosphamide in 16% of the patients. Almost all patients (95%) were transplanted with PBSC. Donor types were matched unrelated donor (MUD, 59%), sibling (32%), or haploidentical (haplo 8%). With a median follow-up of 4.3 years (CI 95% [3.2-5.2]), the 4y OS, PFS, RI and NRM were 54% (CI 95% [46-62]), 46% (CI 95% [37-54]), 23% (CI 95% [16-31]) and 32% (CI 95% [24-40]), respectively. The acute GVHD grade 2-4 and 3-4 rate were 31% (CI 95% [23-38]) and 17% (CI 95% [11-23]), respectively. Extensive chronic GVHD was reported in 40% (CI 95% [32-48]) of the patients at 2 years. At 10y, OS, PFS and GVHD-free, relapse-free survival (GFRFS) were 51% (CI 95% [42-60]), 39% (CI 95% [29-49]) and 30% (CI 95% [21-39]), respectively.

Our work confirms in a large cohort that ASCT and allo-HSCT lead to durable disease control in selected patients with MZL, at the cost of significant toxicity. These results provide the benchmark against which to compare the outcome of new therapies.