Waldenström's Macroglobulinemia (WM) is a rare low-grade B- cell non -Hodgkin lymphoma. Novel therapies have achieved prolonged progression-free (PFS) and overall (OS) survivals. The future role of haemopoietic stem cell transplantation (HSCT), autologous (AHSCT) and allogeneic (allo-HSCT) in the era of the new therapeutic advances needs a critical discussion.

The aim of this retrospective analysis was to assess the trends in HSCT for patients with WM and the longer-term survival outcomes.

In the EBMT registry, 772 patients underwent AHSCT between 2000 and 2021 (218 patients were transplanted between 2000-2010, 290 between 2010-2015 and 264 between 2015-2021). The median age was 57 years (IQR: 50-62), 72% were male and the median time from diagnosis to AHSCT was 24 months (IQR: 11-58). The number of prior therapy lines was, 1 in 24%, 2 in 39% and ≥3 in 37% of the patients. Disease status at AHSCT was ≥VGPR in 36%, PR in 52%, primary or relapse refractory disease (PRRD) in 12%. Karnofsky performance status (KPS) was <90 in 24%. Conditioning regimen included BEAM in 54%, Melphalan in 17%, EAM in 7%, FEAM in 4%, BuCy in 4%, BeEAM in 3%, ThioBCNU in 3%, TBI based in 4% and other in 4%. Peripheral hematopoietic stem cells (HSC) source was used in 99% of the cases. The median follow-up was 4.6 years (95%CI: 3.9-5.3). At 2, 5 and 10 years the estimated OS rates were 89.4%, 70.4% and 55.3% and PFS 68.2%, 46.9% and 31.2%. The relapse rates (RR) were 28.8%, 48.6% and 61.8% and the Non-Relapse Mortality (NRM) 3%, 4.5%, 7.1% at 2, 5 and 10 years respectively. From the multivariate analysis, the time from diagnosis to AHSCT was the only significant factor impacting PFS (HR: 1.39, 95% CI:1.03 - 1.87, p= 0.031) and RR (HR: 1.39, 95% CI:1.02-1.90, p= 0.039). Of the 772 patients, 555 (71.89%) were alive. The cause of death was, progressive disease in 143/772 (18.5%) patients, infection in 21 (2.7%), transplant related in 1.16% and secondary malignancy in 1.81%.

In the EBMT registry, 330 patients transplanted with Allo-HSCT between 2000-2021 were identified (117 patients transplanted between 2000-2010, 125 between 2010-2015 and 88 between 2015-2021). The median age was 55years (IQR: 45 -60), 73% were male and the median time from diagnosis to allo-HSCT was 44 months (IQR: 19-95). 11% received 1, 20% had 2 and 68% ≥3 therapy lines prior to allo-HSCT, whilst 21% failed previous AHSCT. Disease status at the allo-HSCT was ≥VGPR in 30%, PR in 45% and PRRD in 26%. KPS was <90 in 25%. Conditioning regimen was TBI based in 61%. Reduced Intensity conditioning (RIC) was administered in 63% and myeloablative conditioning (MAC) in 37%. Stem cell source was peripheral blood in 89% and the donor was matched related in 43%, matched unrelated in 46%, and haploidentical in 9%. With a median follow-up of 8.3years (95% CI: 6.7-9.1) the 2, 5, 10 years estimated OS rates were 62.9%, 54.0%, 47.3% and the PFS 58.7%, 44.6%, 34.7%. The RR were 21.0%, 31.1%, 37.3% and the NRM 20.2%, 24.3% and 27.98% at 2, 5 and 10 years respectively. The incidence of acute graft versus host disease (aGVHD) grade II-IV was 26.7% (grade III-IV, 12,6%) and the cumulative incidence of chronic GVHD (cGVHD) at 1, 2 and 5 years was 33.4%, 42.4%, 45.5%, and that of extensive cGVHD 11.4%, 18.2% and 22.8% respectively. Good KPS >90 (HR:0.59, 95% CI: 0.39-0.87, p= 0.009), was associated with significantly better OS, whilst having PRRD status at allo-HSCT with worse OS (HR: 1.85, 95% CI: 1.12-3.08, p=0.017), PFS ( HR: 1.95, 95%CI: 1.20-3.16, p=0.007) and RR rates (HR: 2.04, 95% CI: 1.11-3.76, p= 0.023). HLA mismatched HSC donor type was associated with significantly higher incidence of cGVHD (HR: 0.26, 95% CI: 0.08-0.87, p=0.029).

In the era of BTK and BCL2 inhibitors, chemo-immunotherapies and forthcoming T cell engagers with bispecific antibodies and CART cell therapies in lymphomas, it is challenging to define the role or timing for-HSCT in WM treatment pathway. This EBMT real world retrospective study showed that, a small group of HSCT eligible patients, transplanted based on local center treatment criteria, have achieved prolong OS and PFS survival with acceptable toxicities.

Disclosures

Moukalled:Amgen: Honoraria; Janssen: Honoraria. Nur:Vertex: Speakers Bureau; Novartis: Research Funding. Vucinic:Gilead/Kite, Janssen, BMS Celgene, Novartis: Consultancy, Honoraria; Amgen: Honoraria, Other: Travel grant. Einsele:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria; Sanofi: Honoraria; Celgene/Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Glass:Roche, Kite Gilead, BMS: Other: travel support ; Riemser, Roche: Other: grants ; Kite Gilead, Novartis, BMS, Roche, Miltenyi, Incyte: Honoraria. Bazarbachi:Pfizer: Research Funding; Biologix: Research Funding; Amgen: Honoraria; Takeda: Honoraria; Jansen: Honoraria, Research Funding; Caribou: Honoraria; Roche: Honoraria, Research Funding.

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2024
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