Carfilzomib-induced thrombotic microangiopathy (TMA): an under-recognised spectrum of disease from microangiopathic haemolysis to subclinical TMA - Report - MDSpire
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Carfilzomib-induced thrombotic microangiopathy (TMA): an under-recognised spectrum of disease from microangiopathic haemolysis to subclinical TMA
Thrombotic Microangiopathy Spectrum in Carfilzomib-Treated Multiple Myeloma Patients
Overview
Carfilzomib treatment in multiple myeloma patients is associated with a spectrum of thrombotic microangiopathy (TMA) manifestations, ranging from low-grade microangiopathic hemolytic anemia (MAHA) to severe TMA with organ damage. In a retrospective study of 31 patients, 35.5% developed MAHA, with 6.5% progressing to severe TMA, often accompanied by acute kidney injury (AKI).
Background
Carfilzomib, an irreversible proteasome inhibitor, is effective for relapsed multiple myeloma but can induce TMA, characterized by microangiopathic hemolytic anemia and end organ damage, particularly renal injury. The pathogenesis involves complement dysregulation and VEGF reduction leading to endothelial injury and microvascular thrombosis. Patient factors such as complement gene variants may increase susceptibility. Recognition of a spectrum from asymptomatic MAHA to overt TMA is critical for management.
Data Highlights
Parameter
MAHA Affected (n=11)
Unaffected (n=20)
p-value
Mean Age (years)
72
64
0.02
Median Overall Survival (months)
21
21.5
NS
Patients with AKI (%)
45%
0%
Not stated
Severe TMA Cases
2 (6.5%)
0
Not stated
Key Findings
35.5% of carfilzomib-treated patients developed MAHA, with 6.5% progressing to severe TMA.
MAHA episodes were often low-grade, brief, and sometimes asymptomatic, with occasional schistocytes and no elevated bilirubin.
AKI occurred in 45% of patients with low-grade MAHA, indicating subclinical TMA.
Older age was significantly associated with MAHA development (mean 72 vs 64 years, p=0.02).
Severe TMA cases presented with marked hemolysis, severe AKI, and cardiac dysfunction; one responded well to eculizumab treatment.
Carfilzomib continuation during low-grade MAHA episodes was generally tolerated without immediate complications.
Clinical Implications
Clinicians should monitor for a spectrum of TMA manifestations in patients receiving carfilzomib, including subtle signs of MAHA and AKI. Early recognition and differentiation from myeloma progression or infection are essential. In severe cases, complement inhibition with eculizumab may be beneficial, while low-grade MAHA may not necessitate immediate treatment modification.
Conclusion
Carfilzomib-associated TMA encompasses a range from asymptomatic MAHA to severe organ-threatening disease. Awareness and timely diagnosis can guide appropriate management to mitigate morbidity and optimize outcomes in multiple myeloma patients.
References
Author/Source/Year -- Thrombotic Microangiopathy Associated with Carfilzomib
