Kidney Week

Abstract: SA-PO684

Obinutuzumab in Pediatric Idiopathic Nephrotic Syndrome Resistant to Rituximab

Session Information

• Pediatric Glomerular Disease
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1700 Pediatric Nephrology

Authors

• Prim, Benjamin, APHP, Robert-Debre Hospital, Paris, France

Benjamin Prim,

• Dossier, Claire, APHP, Robert-Debre Hospital, Paris, France

Claire Dossier,

• Moreau, Christelle, AP-HP, Robert-Debre Hospital, Paris, France

Christelle Moreau,

• Kwon, Theresa, APHP, Robert-Debre Hospital, Paris, France

Theresa Kwon,

• Couderc, Anne, APHP, Robert-Debre Hospital, Paris, France

Anne Couderc,

• Alexandra, Cambier, APHP, Robert-Debre Hospital, Paris, France

Cambier Alexandra,

• Baudouin, Veronique, APHP, Robert-Debre Hospital, Paris, France

Veronique Baudouin,

• Maisin, Anne Francoise, APHP, Robert-Debre Hospital, Paris, France

Anne Francoise Maisin,

• Deschênes, Georges, APHP, Robert-Debre Hospital, Paris, France

Georges Deschênes,

Background

B-cell depletion with rituximab (RTX) induces sustained remission in children with Steroid Dependant or Frequent Relapsing Nephrotic Syndrome (SD/FRNS). However, most patients relapse after B-cell recovery and some patients do not achieve B-cell depletion. Obinutuzumab (OBZ) is a 2^nd generation glycoengineered anti CD20 monoclonal antibody, with higher in vitro B-cell cytotoxicity, that might be more effective in patients with autoimmune diseases. We report the results of a pilot study of OBZ in pediatric patients with FR/SDNS aiming at assessing both the safety and efficacy of OBZ in patients with prior resistance, intolerance or failure to rituximab.

Methods

Patients received an infusion of 300mg/1,73m² of obinutuzumab, after premedication. All other immunosuppressive therapies were discontinued within two months, and biological monitoring performed monthly until B-cell recovery.

Results

12 patients with SD/FRNS were included and followed for a median duration of 8.0 months [IQ 5.9-12.1]. Median ages at INS onset, first RTX and first OBZ injection were of 3.8, 8.8 and 9.3 years old, respectively. Indication for OBZ were intolerance to RTX (n=1), no B-cell depletion (n=4) or short depletion <3 months (n=4) or early relapse after prolonged B-cell depletion (n=3). B-cell depletion was achieved in all patients. At last follow up, B-cell recovery had occurred in 7 patients after a median depletion of 6 months [IQ 5.2-7.9]. B-cell depletion after OBZ was longer in all patients compared to prior RTX (p = 0,0013). 6/7 patients remained relapse-free with median follow up of 3.6 months after B-cell recovery. Mild infusion reactions were reported in 3/12 patients. Neutropenia within 500-1000/mm³ occurred in 3/12 patients. 2 patients received IV immunoglobulins because of hypo-IgG and 5 patients had hypo-IgM. One patient was hospitalised for pneumonia, with negative bacterial and viral testing and improved with antibiotics.

Conclusion

Obinutuzumab induced peripheral B-cell depletion in SD/FRNS patients resistant to rituximab. A single low dose injection resulted in longer B-cell depletion compared to rituximab. However, short term and long term immunological and infectious side effects have to be closely monitored.