Abstract: SA-PO184
Monoclonal Gammopathy-Associated Thrombotic Microangiopathy
Session Information
- Onco-Nephrology: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Leung, Nelson, Mayo Clinic, Rochester, Minnesota, United States
- Glezerman, Ilya, Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Bijol, Vanesa, Northwell Health Hofstra University, Lake Success, New York, United States
- Garceau, Daniel, IUCPQ, Lac Beauport, Quebec, Canada
- Hassoun, Hani, Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Dispenzieri, Angela, Mayo Clinic, Rochester, Minnesota, United States
- Jhaveri, Kenar D., Northwell Health Sys, Great Neck, New York, United States
Background
Thrombotic microangiopathy (TMA) is characterized by end-organ damage and classic histopathologic findings secondary to endothelial injury. Microangiopathic hemolytic anemia (MAHA) often accompanies the TMA. TMA in the setting of monoclonal gammopathy has been reported after hematopoietic stem cell transplant or with proteasome inhibitors in multiple myeloma (MM) but it is less clear if the monoclonal gammopathy itself may be involved in pathogenesis.
Methods
Cases were obtained from 6 institutions in the United States and Canada. TMA was confirmed histologically (kidney biopsy) or evidence of MAHA with thrombocytopenia (platelet count less than 150 x 109/L) and schistocytes, elevated lactate dehydrogenase (LDH), decreased haptoglobin, and indirect hyperbilirubinemia.
Results
Of the 9 patients, (33.3%) were female. The median age was 66 years. Five patients had MM (4 were treatment naive, 1 previously received melphalan and prednisone), one had Waldenstrom macroglobulinemia (WM), and 3 had monoclonal gammopathy of undetermined significance. The patient with WM had previously been treated with cyclophosphamide, rituximab and dexamethasone. No patient had otherwise received any medication associated with drug-induced TMA.
All patients had renal involvement and a median creatinine of 3.3 mg/dl. Seven patients had a kidney biopsy and all demonstrated TMA. Median hemoglobin and platelet count were 108 g/L and 147 x 109/L, respectively. Six patients had thrombocytopenia but only 4 had evidence of MAHA. No patient had GI symptoms. ADAMTS13 level was only obtained in 1 patient and was non-deficient at 27%. Complement levels (C3, C4, total complement) were normal in 5 patients, and 1 patient had a low C4. Genetic testing for mutations in the alternative complement pathway were performed in 2 patients and were normal.
Three patients were treated with plasma exchange, 1 patient initialy improved but died of multiorgan failure 6 days after presentation. One patient is awaiting treatment plan from hematology. The others have had resolution of TMA without recurrence after treatment of their disease. None of the patients received eculizumab
Conclusion
This study suggests that monoclonal gammopathies are assoicated with TMA. Disease-directed therapy should be considered first-line treatment of TMA, in addition to PLEX if there is ADAMTS13 deficiency.
Funding
- Commercial Support – Takeda, Pfizer, Prothena, Celgene, Janssen, and Alnylam