A case of treatment‐resistant membranous nephropathy associated with graft versus host disease successfully treated with daratumumab

Benoit, Stefanie; Khandelwal, Pooja; Grimley, Michael

doi:10.1111/petr.14263

Cited by 11 publications

(5 citation statements)

References 19 publications

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“…The relevance of targeting long-lived plasmacells in proteinuric disease, such as lupus nephritis ( 79 , 80 ) and membranous neophropathy ( 81 ), have already been reported in previous clinical reports. Unlike to lupus nephritis and membranous neophropathy, that represent clear examples of autoantibodies mediated disease, the role of long-lived plasmacells in SRNS is not completely explored.…”

Section: New Hypothesis-driven Treatment Combining Rituximab and Dara...mentioning

confidence: 76%

Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment

Angeletti,

Bruschi,

Kajana

et al. 2023

Front. Immunol.

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Nephrotic syndrome affects about 2–7 per 100,000 children yearly and accounts for less than 15% of end stage kidney disease. Steroids still represent the cornerstone of therapy achieving remission in 75–90% of the cases The remaining part result as steroid resistant nephrotic syndrome, characterized by the elevated risk of developing end stage kidney disease and frequently presenting disease recurrence in case of kidney transplant. The pathogenesis of nephrotic syndrome is still far to be elucidated, however, efficacy of immune treatments provided the basis to suggest the involvement of the immune system in the pathogenesis of the disease. Based on these substrates, more immune drugs, further than steroids, were administered in steroid resistant nephrotic syndrome, such as antiproliferative and alkylating agents or calcineurin inhibitors. However, such treatments failed in inducing a sustained remission. In last two decades, the developments of monoclonal antibodies, including the anti-CD20 rituximab and inhibitor of B7-1 abatacept, represented a valid opportunity of treatment. However, also the effectiveness of biologics resulted limited. We here propose a new hypothesis-driven treatment based on the combining administration of rituximab with the anti-CD38 monoclonal antibody daratumumab (NCT05704400), sustained by the hypothesis to target the entire B-cells subtypes pool, including the long-lived plasmacells.

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Section: New Hypothesis-driven Treatment Combining Rituximab and Dara...mentioning

confidence: 76%

Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment

Angeletti,

Bruschi,

Kajana

et al. 2023

Front. Immunol.

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“…This treatment has allowed a 60% relapse‐free survival at 2 years without any oral immunosuppressive drugs 9 . Daratumumab efficiency has also been reported in a case of post‐hematopoietic cell transplantation membranous nephropathy resistant to rituximab 18 …”

Section: Discussionmentioning

confidence: 92%

“…9 Daratumumab efficiency has also been reported in a case of post-hematopoietic cell transplantation membranous nephropathy resistant to rituximab. 18 Thus, the pathophysiological rational, data from daratumumab clinical studies and the fact that all common treatments have already F I G U R E 1 Evolution of urinary protein/creatinine ratio and IgG level after renal transplantation depending on immunosuppressive treatment.…”

Section: Recent Data Have Highlighted the Major Role Of B Cells In Insmentioning

confidence: 99%

Successful global anti‐B‐cell strategy with daratumumab in a patient with post‐transplant nephrotic syndrome recurrence unresponsive to immunoadsorption and obinutuzumab

Delbet

Hogan

Parmentier

et al. 2023

Pediatric Transplantation

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Background Steroid‐resistant nephrotic syndrome recurrence post‐transplant unresponsive to immunoadsorption is a dilemma, and no reliable treatment strategy has been identified to induce remission so far. Case presentation A 2‐year‐old girl presented first with idiopathic nephrotic syndrome. She did not reach remission after 30 days of oral steroids and remained resistant to steroid pulses, oral tacrolimus, IV cyclosporine, and to 30 sessions of plasma exchange. Bilateral nephrectomy was performed because of extrarenal complications. Two years later, she received an allograft from a deceased donor and idiopathic nephrotic syndrome relapsed immediately post‐transplantation. She did not reach remission after immunosuppressive therapy including tacrolimus, mycophenolate mofetil, methylprednisolone pulses, daily immunoadsorption, and B‐cell depletion. She received obinutuzumab 1 g/1.73 m2 injections weekly for 3 weeks and then daratumumab 1 g/1.73 m2 weekly for 4 weeks. One week after the last daratumumab infusion, urine protein/creatinine ratio began to decrease. Proteinuria was negative for the first time at Day 99. Immunoadsorption was stopped 147 days after, and she remained relapse‐free at last follow‐up (18 months post‐transplantation). The treatment was complicated by a pneumocystis jirovecii pneumonia with a favorable outcome and persistent hypogammaglobulinemia. Conclusion A obinutuzumab and daratumumab combination seems to be a promising strategy in post‐transplantation SRNS recurrence without response to standard treatment options.

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“…The successful removal of CD38 suggests that resident plasma cells producing allogeneic antibodies may significantly contribute to the complexity of treating this specific ailment. In conclusion, Daratumumab may offer a promising new treatment option for individuals unresponsive to standard treatments (18).…”

Section: Membranous Nephropathymentioning

confidence: 95%

Application of CD38 monoclonal antibody in kidney disease

Chen,

Xu,

Shou

2024

Front. Immunol.

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CD38 antigen is a glycoprotein that found on the surface of several immune cells, and this property makes its monoclonal antibodies have the effect of targeted elimination of immune cells. Therefore, the CD38 monoclonal antibody (such as daratumumab, Isatuximab) becomes a new treatment option for membranous nephropathy, lupus nephritis, renal transplantation, and other refractory kidney diseases. This review summarizes the application of CD38 monoclonal antibodies in different kidney diseases and highlights future prospects.

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A case of treatment‐resistant membranous nephropathy associated with graft versus host disease successfully treated with daratumumab

Cited by 11 publications

References 19 publications

Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment

Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment

Successful global anti‐B‐cell strategy with daratumumab in a patient with post‐transplant nephrotic syndrome recurrence unresponsive to immunoadsorption and obinutuzumab

Application of CD38 monoclonal antibody in kidney disease

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