Obinutuzumab Rescue in Rituximab Resistant Mixed Cryoglobulinemia
Notice bibliographique
Résumé
We previously reported a persistent mixed cryoglobulinemic membranoproliferative glomerulonephritis secondary to a monoclonal gammopathy of renal significance despite hepatitis C eradication.1Pelletier K. et al.Persistent mixed cryoglobulinemia despite successful treatment of hepatitis C, aggressive B-cell-directed therapies, and long-term plasma exchanges.Kidney Int Rep. 2019; 4: 1194-1198Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar While initially responsive to rituximab, the patient became refractory to it, and subsequently failed cyclophosphamide, bortezomib and bendamustine. Azathioprine proved partially efficacious as demonstrated by a relapse within a month of its cessation in order to administer bendamustine. He remained dependent on weekly plasmapheresis. To improve disease control, obinutuzumab was added to azathioprine. Four doses of 1 g were given every 3 weeks, followed by 3 additional doses every 8 weeks. This translated into lasting reductions in proteinuria, rheumatoid factor and serum free light chain ratio (Figure 1). Plasmapheresis requirements decreased, and azathioprine and prednisone doses were tapered. At 1-year post obinutuzumab therapy, CD19+/CD20+ lymphocytes remain undetectable. No opportunistic infection occurred. Obinutuzumab is a novel humanized type II anti-CD20 monoclonal antibody with superior B-cell depleting capabilities, mediated by enhanced direct cell death via complement activation and antibody-dependent phagocytosis.2Freeman C.L. Sehn L.H. A tale of two antibodies: obinutuzumab versus rituximab.Br J Haematol. 2018; 182: 29-45Crossref PubMed Scopus (37) Google Scholar Although only approved for the treatment of hematological malignancies, it is being investigated in lupus nephritis and membranous nephropathy. A case of chronic lymphoid leukemia related immune-complex mediated membranoproliferative glomerulonephritis was successfully treated with it.3Jain P. et al.Membranoproliferative glomerulonephritis and acute renal failure in a patient with chronic lymphocytic leukemia: Response to obinutuzumab.Hematol Oncol Stem Cell Ther. 2017; 10: 151-154Crossref PubMed Scopus (3) Google Scholar To our knowledge, this is the first report of a response to obinutuzumab in refractory monoclonal gammopathy of renal significance. It reduced the production of pathogenic monoclonal RF permitting the weaning of concomitant therapies. Rescue therapy with obinutuzumab, or other new B-cell depleting therapies, should be considered in glomerular diseases where rituximab is indicated but has failed. Persistent Mixed Cryoglobulinemia Despite Successful Treatment of Hepatitis C, Aggressive B-Cell–Directed Therapies, and Long-term Plasma ExchangesKidney International ReportsVol. 4Issue 8PreviewCryoglobulins are Igs that precipitate in cold temperature. Three subsets have been described: type I consists of only monoclonal Ig, usually due to monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia.1 Type II cryoglobulins contain polyclonal IgG and a monoclonal IgM with rheumatoid factor (RF) activity directed against the IgG, whereas type III contains both polyclonal IgG and IgM RF.2 Types II and III, also called mixed cryoglobulinemia, result in most cases from a B-cell proliferative process in the setting of persistent immune activation triggered by chronic hepatitis C virus (HCV) infection. Full-Text PDF Open Access
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,008 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».