Introduction:

High grade transformation of Waldenstrom's Macroglobulinemia (tWM) is a rare but serious complication and there is limited information on outcomes. The aim of this study was to analyse the outcomes of stem cell and cellular therapies with Autologous (ASCT),Allogeneic haemopoietic stem cell transplantation (AlloSCT) and CAR T Cell therapies for patients with tWM to high grade Non-Hodgkin Lymphoma (HGNHL). Background: This is a LWP EBMT retrospective study, reporting the real-world outcomes in 310 patients with tWM who met the inclusion criteria, reported to the European Group for Blood and Marrow Transplantation (EBMT) registry and treated with ASCT, Allo-SCT or CAR T Cell therapy. Methods and results: Participating EBMT centers submitted data for patients reported with confirmed diagnosis of tWM. 217 were treated with ASCT, 49 with alloSCT between 2010-2023 and 44 with CART Cell therapy between 2023 -2024. Results: Of the 217 patients treated with ASCT 122 were male with a median age of 53.9 (29.2-74.1) years and a median time from diagnosis to ASCT of 8.1 (2.4-202) months. 37% had the ASCT following 1 line, 43% 2nd line and 20% following 3rd treatment line and 64.4% had anthracycline based regimen prior to ASCT. The IPI score was low risk in 19%, low-intermediate in 31%, high-intermediate in 6% and high risk in 27%. Karnofsky performance status (KFS) was ≥90 in 67% of the patients. The Haemopoietic stem cell transplantation Comorbidity index (HSCT CI) was 0 in 57%, 1-2 in 23% and ≥3 in 21%. The disease status was CR in 118 patients (56.7%), Very Good Partial Response (VGPR) /Partial Response (PR) in 57 (27.4%), Primary Refractory (PRD) / Progressive Disease (PD) in 30 (14.4%) and in 12 (1.5%) it was not available (NA). The conditioning was BEAM based in 63%. The estimated Overall Survival (OS) was 68.9%, Progression Free Survival (PFS) was 59.5%, Relapse Incidence (RI) was 36.3% and Non-Relapse Mortality (NRM) was 4.2% at 2 years respectively. Of the 44 patients treated with CAR T Cell therapy, 29 (66%) were male with a median age of 61 (23-71) years, and a median time from diagnosis to the therapy of 12.8 (3.3- 198.2) months. 37% had CART following 1 prior line, 43% after 2 and 20% after ≥3 prior treatment lines and 84% had anthracycline-based chemotherapy prior to CART. The IPI score was low risk in 15%, low-intermediate in 8%, high-intermediate in 38.5% and high risk in 38.5%. KFS was ≥90 in 50% of the patients. The HSCT CI was 0 in 62.5%, 1-2 in 12.5% and ≥3 in 25%. The disease status was CR in 3 patients (7%), VGPR / PR in 6 (13.5%), PRD / PD in 33 (75%) and in 2 (4.5%) it was not available. The median follow up was 3 (0-6) months, OS was 68.5%, PFS was 35.8%, RI was 59.7% and NRM was 4.5% at 1 year respectively. Of the 49 patients treated with Allo-SCT 33 were male with a median age of 47.6 (38.4-57.4) years and a median time from diagnosis to Allo-SCT of 13.6 (3.1-167) months. 43% had the Allo-SCT following 1 line, 33% 2 line and 24% following ≥3 treatment lines and 55% had anthracycline based therapy regimen prior to Allo-SCT. 39% had a previous failed ASCT. KFS was ≥90 in 60% of the patients. The HSCT CI index was 0 in 46%, 1-2 in 25% and ≥3 in 29%. The disease status was CR in 23 patients (47%), VGPR / PR in 14 (29%), PRD / PD in 9 (18%) and in 3 (6%) it was not available. The conditioning was myeloablative (MAC) in 30 patients (61%), and reduced intensity conditioning (RIC) in 19 (39%) and 14 (29%) patients had TBI based regimen. The stem cell donor was sibling in 18 (37%), unrelated in 24 (49%) and haploidentical in 7 (14%). 29 (63%) patients had in vivo T cell depletion (of whom 21 (46%) with ATG, 8 (17%) with Campath) and 5 had post-transplant cyclophosphamide (PTCY). With a median follow up of 7.8 years (3.1-8.2) the estimated OS was 43%, PFS was 29%, RI was 55%, NRM was 17% and graft versus host disease (GVHD)-free/relapse-free survival (GRFS) 21% at 2 years respectively. The incidence of acute GVHD grade III/IV was 12% and chronic extended GVHD was 9%. Conclusion: The limited available data reported poor outcomes of transformed WM to HGNHL. This EBMT retrospective analysis, the largest reported cohort of transformed WM patients to date, showed that these patients could be rescued with cellular therapies.

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2025
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