Associate Professor Rush University Medical Center Chicago, Illinois, United States
Introduction: Soluble Urokinase Plasminogen Activator Receptor (SuPAR) is an inflammatory mediator of kidney injury in various clinical settings. SuPar levels have been found to be higher in patients with multiple myeloma (MM) when compared to healthy controls, and have been correlated with worse kidney function in MM pts. However, data is limited to its role in mediating kidney injury and ultimately renal recovery. In this pilot study we compared baseline suPAR values between patients with MM requiring treatment and those with smoldering state or MGUS. We also determined whether suPAR levels correlate with the level of renal impairment, response to myeloma treatment and kidney recovery.
Methods: SuPAR levels were measured in patients at the time of diagnosis, including seven patients with smoldering myeloma or MGUS and 11 patients with newly diagnosed MM requiring treatment. Among patients undergoing treatment for MM suPAR levels were repeated after induction therapy and after autologous stem cell transplant (ASCT). Renal function and MM response to treatment were assessed at the same time points.
Results: Patients with smoldering myeloma and MGUS had lower average suPAR level 3.35 ng/ml (SD +/- 1.78) than patients with MM requiring treatment 4.5 ng/ml (SD +/- 1.97) at baseline, but it was not statistically significant (p 0.22). Average suPAR level was higher in patients with glomerular filtration rate (GFR) of less than 40 ml/min/1.73 m2 compared to the rest of study subjects 3.85 (SD +/- 1.8) vs 4.74 (SD +/- 2.44), but also not statistically significant (0.49). Four patients in the study underwent treatment for MM and had serial measurements of SuPAR levels. All patients achieved VGPR or better to the induction regimen. Two of the three patients with available data had a decline in suPAR level after induction regimen and kidney function remained stable. One patient had stable suPAR level around 3 ng/ml and showed improvement of kidney function.
Conclusions: This pilot study shows that suPAR levels are elevated both in patients with multiple myeloma requiring treatment and patients with MGUS and smoldering multiple myeloma. We found no difference in suPAR levels in patients with MM and GFR of less than 40 ml/min/1.73 m2 vs more than 40 ml/min/1.73 m2. A suPAR level around 3 ng/ml before or after treatment appears to be beneficial for stable or improving kidney function. This finding supports further study of suPAR as a prognostic factor in multiple myeloma. SuPAR effect on myeloma prognosis and GFR in patients with renal impairment, will be evaluated in a large phase 2 trial Bortezomib, Isatuximab, Cyclophosphamide and Dexamethasone Induction in Transplant-Eligible Multiple Myeloma Patients (NCT04240054).
