Clinical Trial: Isatuximab in Monoclonal Gammopathy of Renal Significance (MGRS)

A clinical trial aims to prevent kidney damage using isatuximab in a condition called Monoclonal Gammopathy of Renal Signifcance. 

Monoclonal Gammopathies (MG) are disorders characterized by the production of abnormal immunoglobulins, also known as monoclonal proteins, that do not meet the criteria for multiple myeloma. Recently a new entity has been identified in this group, the Monoclonal Gammopathy of Renal Significance (MGRS), in which the monoclonal proteins accumulate on the kidney and cause kidney damage without meeting the diagnostic criteria for multiple myeloma. Currently, the reason for this protein accumulation is unknown. 

Even if a Monoclonal Gammopathy does not initially require therapy from the standpoint of the tumor, the current guidelines agree that treatment should be considered obligatory and should begin as soon as possible when there is kidney damage. 

Currently, the treatment options for MGRS are limited, but during the last ten years, we have seen a revolution in the treatment of multiple myeloma and the use of anti-CD38 treatments. Understanding the effect of isatuximab, an anti-CD38 monoclonal antibody, in MGRS can help us significantly improve the treatment opportunities of patients with this disease.

About the Study

This study is evaluating the effect of isatuximab (Sarclisa), an anti-CD38 monoclonal antibody, on kidney outcomes in patients with monoclonal gammopathy of renal significance (MGRS) and determine any abnormalities that could cause the production of abnormal proteins that collect in the kidney (renal parenchyma), and cause kidney damage. 

• There is only one group in this study, which will receive isatuximab for six months and will be followed for an additional (one) year post-therapy to evaluate the renal outcome
• The patients in this study will also have immunoglobulin gene mutations tested by next generation sequencing up to four weeks prior to treatment

The study will determine: 

• Overall Renal Response Rate, defined as a decrease in 24-hour proteinuria (measurement of protein in the urine) by >50% at any point post-therapy
• The number of adverse events (side effects) related to the therapy
• The percentage of participants with immunoglobulin gene mutations determined by next generation sequencing

Patients who can join the study include patients with: 

• Renal biopsy-proven diagnosis of an MGRS disorder
• Measurable proteinuria ≥ 1 gram over 24 hours
• Newly diagnosed as well as patients with previous therapy but persistent renal dysfunction and persistent proteinuria ≥ 1 gram over 24 hours 
• Patients who received a prior CD38 antibody therapy are not eligible for this study.
• A kidney function equal to or greater than an Estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m2
• Participants must have normal organ and marrow function

For more information about the inclusion/exclusion criteria, click here.

The study is open at Massachusetts General Hospital (Renal Associates Clinic), and Columbia University Irving Medical Center.