Persistent Immunoparesis Reduces OS Post Allo-SCT in Patients With MM

Prolonged immunoparesis was associated with reduced overall survival (OS) in patients with multiple myeloma who undergo allogeneic stem cell transplantation (allo-SCT), according to a new study.

The research, published in the Annals of Hematology,¹ could provide an important predictor of patient prognosis following allo-SCT.

Treatment of MM has improved substantially in recent years, but patients with a stage III disease or higher, and those with high-risk cytogenetic abnormalities tend to have limited periods of remission following standard therapy, even with subsequent therapy with new agents, according to corresponding author Matthias Stelljes, MD, of the University of Münster, in Germany. Allogeneic SCT has been shown to overcome high-risk cytogenetics in many patients, though relapse still occurs in a sizable number of patients, and non-relapse mortality has also been reported in what Stelljes said are concerning numbers.

Timely cellular immune reconstitution has been shown to improve outcomes in patients who undergo allo-SCT, in part because it may enhance graft-versus-myeloma effect, Stelljes and colleagues wrote. However, persistent immunoparesis, which they define as suppression of polyclonal immunoglobulin uninvolved in clonal disease, has been linked with adverse outcomes.

Stelljes and colleagues sought to evaluate outcomes of patients with allo-SCT, and specifically to assess the association of impaired humoral immune constitution (immunoparesis) on post-transplant survival.

To answer the question, the investigators retrospectively analyzed the cases of 90 patients with MM who underwent allo-SCT at the investigators’ medical center between 1999 and 2017.

After 2 years, OS was 52.6% and progression-free survival (PFS) was 36.4%. At 5 years, OS was 38.6% and 25.3%. The median follow-up was 76 months.

Patients who had received more than 2 lines of therapy prior to transplantation had inferior OS and PFS.

“Recent data could demonstrate how varying selective pressure of therapies gives rise to clonal evolution and chemoresistance,” the authors said. “This could be one explanation for the failure of graft-versus-myeloma effect and early relapse in intensively pre-treated patients.”

When it came to immunoparesis, Stelljes and colleagues found that at day 200, prolonged immunoparesis was linked with reduced OS, though not with PFS.

“In our analysis, the worse outcome for patients with immunoparesis at 200 days might be partly explained by the prolonged use of immunosuppressive therapy in this subgroup and, consequently, a higher risk of [non-relapse mortality] due to infection or GvHD,” they said.

The authors added that their observation might also be due to “sub-clinical relapse with expansion of bone marrow myeloma cells and subsequent suppression of normal plasma cells via bone marrow microenvironment factors that are not yet comprehensively understood.”

Stelljes and colleagues concluded that allo-SCT may offer a survival benefit in earlier phases on MM. They said monitoring polyclonal immunoglobulins in the first year post-transplantation might help clinicians better identify patients at higher risk of death and those who need to be more closely monitored.

Reference

Eisfeld C, Eßeling E, Wullenkord R, et al. Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma. Ann Hematol. 2020;99(8):1907-1915. doi:10.1007/s00277-020-04068-5