Exploring the Role of Hematopoietic Stem Cell Transplantation in WM

Waldenström macroglobulinemia (WM) is a rare, low-grade B-cell non-Hodgkin lymphoma, for which novel therapies have significantly improved progression-free survival (PFS) and overall survival (OS). However, the evolving role of hematopoietic stem cell transplantation (HSCT)—both autologous (AHSCT) and allogeneic (allo-HSCT)—requires further clarification amid advancements in targeted and cellular therapies, according to an analysis presented at the 2024 American Society of Hematology Annual Meeting. The retrospective analysis of the EBMT (European Group for Blood and Marrow Transplantation) registry provided valuable insights into the trends and outcomes of HSCT for patients with WM.

Between 2000 and 2021, 772 patients underwent AHSCT. The median age at transplantation was 57 years, with 72% of patients being male. Most patients (76%) received two or more prior therapy lines, and 36% achieved at least very good partial response before transplantation. The estimated OS rates at 2, 5, and 10 years were 89.4%, 70.4%, and 55.3%, respectively, and PFS rates were 68.2%, 46.9%, and 31.2%. Relapse rates increased over time, reaching 61.8% at 10 years; however, nonrelapse mortality (NRM) remained low at 7.1%. The time from diagnosis to AHSCT emerged as a key factor influencing PFS and relapse rates. Despite these challenges, 71.9% of patients were alive at the study’s conclusion, with disease progression being the most common cause of death.

In the same registry, 330 patients underwent allo-HSCT during the study period. These patients were slightly younger, with a median age of 55 years, and had a median of 44 months from diagnosis to transplantation. Unlike patients who underwent AHSCT, 68% of those who underwent allo-HSCT received three or more prior therapy lines, and 21% had previously experienced AHSCT failure. The OS rates at 2, 5, and 10 years were 62.9%, 54.0%, and 47.3%, respectively; PFS rates were 58.7%, 44.6%, and 34.7%. Notably, patients who had undergone allo-HSCT experienced higher rates of NRM (20.2% at 2 years) and chronic graft-versus-host disease (cGVHD), with significant implications for long-term quality of life.

Both AHSCT and allo-HSCT demonstrated prolonged survival for selected patients, despite the advent of targeted therapies, Bruton tyrosine kinase (BTK) and BCL2 inhibitors, and T-cell–based approaches. Factors such as good performance status (Karnofsky Performance Status score  >90) and disease control before transplantation were associated with better outcomes, whereas primary or relapse-refractory disease correlated with worse survival and higher relapse rates. The choice of human leukocyte antigen–mismatched donors increased the risk of chronic GVHD.

“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,” the authors noted.

“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 [sic] OS and PFS survival with acceptable toxicities.”

Reference

Kyriakou C, Fekom M, Khevdelidze M, et al. Long term outcomes of hematopoietic stem cell transplantation in patients with Waldenström’s macroglobulinemia. Abstract #3010. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.