Daratumumab Monotherapy in Severe Patients with AL Amyloidosis and Biopsy-Proven Renal Involvement: A Real Life Experience

Roccatello, Dario; Fenoglio, Roberta; Naretto, Carla; Baldovino, Simone; Sciascia, Savino; Ferro, Michela; Rossi, Daniela

doi:10.3390/jcm9103232

Cited by 7 publications

(6 citation statements)

References 22 publications

(23 reference statements)

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“…Demonstrated to be safe for multiple myeloma patients with renal failure 8–10 and with kidney transplants, 11 its utility in other antibody‐mediated diseases affecting the kidney has been subsequently probed. Examples include membranoproliferative glomerulonephritis with monoclonal immunoglobulin deposits, 12–14 immunoglobulin light‐chain amyloidosis with renal involvement, 15–17 and antibody‐mediated rejection of kidney transplants 18 . In addition, daratumumab has been trialed in combination with obinutuzumab, an antiCD20 monoclonal antibody targeting naïve and memory B cells, as a global anti‐B cell strategy to induce prolonged remission in steroid‐dependent pediatric nephrotic syndrome 19 .…”

Section: Discussionmentioning

confidence: 99%

“…7 Demonstrated to be safe for multiple myeloma patients with renal failure [8][9][10] and with kidney transplants, 11 its utility in other antibody-mediated diseases affecting the kidney has been subsequently probed. Examples include membranoproliferative glomerulonephritis with monoclonal immunoglobulin deposits, [12][13][14] immunoglobulin light-chain amyloidosis with renal involvement, [15][16][17] and antibody-mediated rejection of kidney transplants. 18 In addition, F I G U R E 1 Laboratory biomarkers of MN disease activity after daratumumab.…”

Section: Discussion and Con Clus I On Smentioning

confidence: 99%

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

Benoit

Khandelwal

Grimley

2022

Pediatric Transplantation

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Membranous nephropathy (MN) is the most common cause of glomerulopathy after hematopoietic cell transplantation (HCT). 1 The vast majority of MN occur after allogeneic HCT as a late complication in the setting of graft versus host disease (GVHD). 1 Immune suppression is typically reinitiated in this context, and MN specific therapies often include a combination of steroids, calcineurin inhibitors, mycophenolate mofetil, cyclophosphamide, and/or rituximab. Although remission frequently occurs upon re-initiation of immunosuppression, approximately 20% of patients will fail to respond and may progress to end stage renal disease. 2 Here we report the rapid remission of a treatment-resistant patient with daratumumab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussion and Con Clus I On Smentioning

confidence: 99%

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

Benoit

Khandelwal

Grimley

2022

Pediatric Transplantation

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“…Two phase II clinical trials evaluated daratumumab as a rescue therapy for patients with AL amyloidosis [ 40 , 41 ]. Moreover, once daratumumab became available for multiple myeloma, many relapsed/refractory patients with AL amyloidosis had access to this drug as well, and almost 20 case reports and retrospective series were published in 4 years [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Differently from the frontline trial that evaluated subcutaneous daratumumab, the intravenous drug was employed in these studies.…”

Section: In Vivo Applicationsmentioning

confidence: 99%

Daratumumab in the Treatment of Light-Chain (AL) Amyloidosis

Palladini

Milani

Malavasi

et al. 2021

Cells

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Systemic light-chain (AL) amyloidosis is caused by a small B cell, most commonly a plasma cell (PC), clone that produces toxic light chains (LC) that cause organ dysfunction and deposits in tissues. Due to the production of amyloidogenic, misfolded LC, AL PCs display peculiar biologic features. The small, indolent plasma cell clone is an ideal target for anti-CD38 immunotherapy. A recent phase III randomized study showed that in newly diagnosed patients, the addition of daratumumab to the standard of care increased the rate and depth of the hematologic response and granted more frequent organ responses. In the relapsed/refractory setting, daratumumab alone or as part of combination regimens gave very promising results. It is likely that daratumumab-based regimens will become new standards of care in AL amyloidosis. Another anti-CD38 monoclonal antibody, isatuximab, is at an earlier stage of development as a treatment for AL amyloidosis. The ability to target CD38 on the amyloid PC offers new powerful tools to treat AL amyloidosis. Future studies should define the preferable agents to combine with daratumumab upfront and in the rescue setting and assess the role of maintenance. In this review, we summarize the rationale for using anti-CD38 antibodies in the treatment of AL amyloidosis.

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“…Our group previously reported an initial experience with daratumumab monotherapy in AL amyloidosis in a small series of patients with severe biopsy-proven renal involvement [10]. We hereby report our long-term experience on the effects of a complete course (i.e., 24 administrations) of daratumumab given alone on the deposition of amyloid as evaluated in repeat renal biopsy.…”

Section: Introductionmentioning

confidence: 97%

Histological Kidney Re-Evaluation after Daratumumab Monotherapy for AL Amyloidosis

Fenoglio

Rabajoli

Barreca

et al. 2022

Hemato

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Background: AL amyloidosis is a systemic disorder characterized by extracellular deposition of characteristic fibrils that results in progressive multi-organ failure and premature death. Recently daratumumab has been demonstrating higher hematological and organ response rates when compared to the standard of care. We hereby report our long-term experience on the effects of daratumumab given alone on the deposition of amyloid as evaluated in repeat renal biopsy. Results: Six patients were enrolled. All patients had proteinuria that was associated with renal function impairment in four. After therapy with daratumumab, four patients achieved complete hematological response and two had partial hematological response at the end of treatment. With regard to renal response, four out of six patients achieved an organ response; one patient had fluctuating proteinuria levels and did not meet the needed criteria at the end of the treatment and the last patient, who was already in dialysis at the time of therapy initiation, remained on dialysis despite complete hematological and cardiac responses. A significant decrease in 24-h proteinuria from 7.9 g/24 h to 1.1 (p < 0.005) with stabilization or improvement of sCr (from 1.5 mg/dL to 1.2 mg/dL; p = 0.34) were observed. All patients underwent a repeat biopsy after 24 administrations of daratumumab. In five patients, the repeat biopsy showed unchanged features; while in one it showed an improvement. Conclusions: Our data, based on real life experience, show that daratumumab monotherapy can be an effective therapeutic option. It is capable not only of achieving a substantial rate of renal improvement in pre-treated and naïve patients, but also of limiting renal deposition

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Daratumumab Monotherapy in Severe Patients with AL Amyloidosis and Biopsy-Proven Renal Involvement: A Real Life Experience

Cited by 7 publications

References 22 publications

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

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

Daratumumab in the Treatment of Light-Chain (AL) Amyloidosis

Histological Kidney Re-Evaluation after Daratumumab Monotherapy for AL Amyloidosis

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