Carfilzomib

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 74-year-old man developed posterior reversible leucoencephalopathy syndrome (PRES) during treatment with carfilzomib.

The man, who had an 18 years history of IgG κ-multiple myeloma, had ben receiving treatment with carfilzomib [dosage and route not stated] and concomitant dexamethasone every 3 weeks for 8 months. On 01 April 2020, he presented with dry cough, fever and asthenia. Therefore, carfilzomib and dexamethasone dose was not administered. Subsequently, he was diagnosed with severe bilateral pneumonia due to SARS-CoV-2 infection. Blood test showed ferritin 4 242 ng/mL, IL-6 85.97 pg/mL and lymphocytes 130 cells/μL. Following his admission, he received off-label treatment with ceftriaxone, dexamethasone, enoxaparin-sodium [enoxaparin], hydroxychloroquine and lopinavir/ritonavir. He remained stable during the initial treatment; however, his condition worsened despite the treatment. He developed severe lymphopenia (30–40 cells/μL) and severe anaemia (haemoglobin 7.5 g/dL). On hospital day 15, following improvement in the SARS-CoV-2 infection, he experienced two focal aware motor seizures, which were resolved spontaneously. At that time, his systolic BP was 140−150mm Hg (normal level: 110−120mm Hg). After this episode, he presented with a new focal motor onset seizure and impaired awareness. As his condition persisted, he received anti-epileptic treatment including diazepam, levetiracetam, lacosamide and valproate. However, his condition still persisted. Subsequent cranial CT showed cortical and subcortical hypodensities, with predominance on the parietooccipital regions, which was also affecting the frontal lobe, left basal ganglia, brain stem and cerebellum. He was diagnosed with PRES [duration of treatment to reaction onset not stated]. After 2.5 hours of the onset of the symptoms, his condition was persisting despite the anti-epileptic treatment.

In a view of refractory status epilepticus secondary to PRES, the man received treatment with verapamil. Soon, his impaired awareness resolved. However, he developed upper left limb palsy and cortical blindness, which resolved subsequently. He started receiving maintenance treatment with valproate, levetiracetam and lacosamide, following which he did not experience any further seizure. After 24 hours of the onset of status epilepticus, a lumbar puncture ruled out infection by bacteria or neurotropic viruses, including SARS-Cov2. A brain MRI showed hyperintensities on T2-weighted image and FLAIR sequences, predominantly on frontoparietal and occipital subcortical areas bilaterally, confirming diagnosis of PRES.