Author Of 2 Presentations
P0260 - Obinutuzumab use complicated by progressive multifocal leukoencephalopathy: a case report. (ID 764)
Abstract
Background
Progressive multifocal leukoencephalopathy (PML) is a severe, untreatable, and often fatal brain disease caused by reactivation of the latent John Cunningham virus (JCV). PML is almost exclusively seen in immunosuppressed patients or associated with specific immunotherapies. Obinutuzumab is a humanized anti-CD20 monoclonal antibody approved for use in combination with chlorambucil as treatment of chronic lymphocytic leukemia. As of July 2, 2020, EudraVigilance reports 16 PML cases with obinutuzumab. However, most of these cases represent a carryover effect from previous rituximab therapy.
Objectives
To describe a case of non-carryover obinutuzumab PML occuring in a female patient with chronic lymphocytic leukemia.
Methods
A 76-year-old, HIV-negative female was admitted in our institution in May 2020 for evaluation of progressive cerebellar syndrome. Her husband had noticed progressive neurobehavioral symptoms and insidious onset of ataxia in the beginning of 2020, but neurological symptoms had significantly worsened over the 2 weeks before admission. Her medical history was significant for previously untreated chronic lymphocytic leukemia that was diagnosed in 1996. Due to disease progression, she started obinutuzumab and chlorambucil in April 2020 and received a total of 6 cycles ending in September 2020.
Results
Brain magnetic resonance imaging revealed multiple lesions highly suggestive of PML, as characterized by T2/ FLAIR hyperintensities and T1 hypointensities involving both cerebellar hemispheres as well as the sub-cortical white matter in the right parietal lobe, without gadolinium enhancement and mass effect. PML was confirmed by detection of JCV-DNA in the CSF (81711 copies/ml). Absolute lymphocyte count was 1151/µl. The peripheral CD4+ T-cell count was 651/mm³, CD8+ at 348/mm³. Follow-up MRI at 2 weeks showed progression of the lesion. At the time of writing, neurological deterioration is ongoing and the patient has recently been transferred to a palliative care facility.
Conclusions
This case highlights that PML should be ruled out in any obinutuzumab-treated patient displaying neurological deficits. Although the reported patient had a higher risk to develop PML resulting from the underlying predisposing disease (CLL), it is however conceivable that the introduction of obinutuzumab triggered JCV reactivation and development of PML in the reported case. Further investigations are needed to determine whether PML could be a class effect of anti-CD20 antibodies.
P0264 - Simultaneous bilateral optic neuropathy and myelitis revealing paraneoplastic neurological syndrome associated with multiple onconeuronal antibodies (ID 772)
Abstract
Background
Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer associated with a broad spectrum of clinical manifestations. Optic neuropathy (ON) and myelitis are frequent manifestations of multiple sclerosis (MS) and neuromyelitis optic spectrum disorders (NMOSD) but are considered as non-classical in PNS. Here, we report a case of PNS revealed by simultaneous bilateral ON and myelitis related to multiple co-existing paraneoplastic antibodies (Abs), in the setting of small cell lung cancer (SCLC).
Objectives
To describe a patient with concomitant bilateral ON and myelitis as revealing neurological manifestations of paraneoplastic autoimmunity.
Methods
A 70-year-old man with a 50-pack-year smoking history was admitted because of subacute bilateral and painless vision loss and left lower limb weakness. Visual acuity was 7/10 in the right eye and 3/10 in the left eye. Fundoscopy showed bilateral disc swelling and peripapillary hemorrhages. Brain MRI did not reveal any optic nerve lesion nor lesions suggestive of MS. Spinal cord MRI showed a T2-weighted hyperintensity at the C2 level, with gadolinium enhancement. The visual evoked potentials showed significant bilateral increase of P100 latencies. CSF analysis showed lymphocytic pleocytosis (149 cells/μl), elevated protein concentration (99 mg/dl), and positive CSF-restricted IgG oligoclonal bands. No malignant cells were found in the CSF. Immunologic and infectious workup was unremarkable. Testing for anti-AQP4 and -MOG Abs was negative. Lung cancer was highly suspected on whole body FDG-PET. Transbronchial needle aspiration of hilar lymph nodes revealed SCLC.
Results
The paraneoplastic antibody panel showed a significant signal for anti-Hu Abs in the serum (EUROLINE Neuronal Antigen Profile blots, EUROIMMUN), confirming the diagnosis of PNS. Anti-CV2/CRMP5 and -amphiphysin Abs were also detected, albeit at lower levels. Treatment with intravenous methylprednisolone and plasma exchange resulted in poor clinical improvement. A second malignancy (prostate cancer) was highly suspected but the patient elected to withdraw from further evaluation or treatment and received palliative care at home.
Conclusions
Simultaneous involvement of optic nerves and spinal cord is a rare manifestation of PNS. This presentation should prompt screening for a panel of onconeuronal Abs and for an underlying malignancy, particularly in older adult smokers who are unlikely to have MS or NMOSD.
Presenter Of 2 Presentations
P0260 - Obinutuzumab use complicated by progressive multifocal leukoencephalopathy: a case report. (ID 764)
Abstract
Background
Progressive multifocal leukoencephalopathy (PML) is a severe, untreatable, and often fatal brain disease caused by reactivation of the latent John Cunningham virus (JCV). PML is almost exclusively seen in immunosuppressed patients or associated with specific immunotherapies. Obinutuzumab is a humanized anti-CD20 monoclonal antibody approved for use in combination with chlorambucil as treatment of chronic lymphocytic leukemia. As of July 2, 2020, EudraVigilance reports 16 PML cases with obinutuzumab. However, most of these cases represent a carryover effect from previous rituximab therapy.
Objectives
To describe a case of non-carryover obinutuzumab PML occuring in a female patient with chronic lymphocytic leukemia.
Methods
A 76-year-old, HIV-negative female was admitted in our institution in May 2020 for evaluation of progressive cerebellar syndrome. Her husband had noticed progressive neurobehavioral symptoms and insidious onset of ataxia in the beginning of 2020, but neurological symptoms had significantly worsened over the 2 weeks before admission. Her medical history was significant for previously untreated chronic lymphocytic leukemia that was diagnosed in 1996. Due to disease progression, she started obinutuzumab and chlorambucil in April 2020 and received a total of 6 cycles ending in September 2020.
Results
Brain magnetic resonance imaging revealed multiple lesions highly suggestive of PML, as characterized by T2/ FLAIR hyperintensities and T1 hypointensities involving both cerebellar hemispheres as well as the sub-cortical white matter in the right parietal lobe, without gadolinium enhancement and mass effect. PML was confirmed by detection of JCV-DNA in the CSF (81711 copies/ml). Absolute lymphocyte count was 1151/µl. The peripheral CD4+ T-cell count was 651/mm³, CD8+ at 348/mm³. Follow-up MRI at 2 weeks showed progression of the lesion. At the time of writing, neurological deterioration is ongoing and the patient has recently been transferred to a palliative care facility.
Conclusions
This case highlights that PML should be ruled out in any obinutuzumab-treated patient displaying neurological deficits. Although the reported patient had a higher risk to develop PML resulting from the underlying predisposing disease (CLL), it is however conceivable that the introduction of obinutuzumab triggered JCV reactivation and development of PML in the reported case. Further investigations are needed to determine whether PML could be a class effect of anti-CD20 antibodies.
P0264 - Simultaneous bilateral optic neuropathy and myelitis revealing paraneoplastic neurological syndrome associated with multiple onconeuronal antibodies (ID 772)
Abstract
Background
Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer associated with a broad spectrum of clinical manifestations. Optic neuropathy (ON) and myelitis are frequent manifestations of multiple sclerosis (MS) and neuromyelitis optic spectrum disorders (NMOSD) but are considered as non-classical in PNS. Here, we report a case of PNS revealed by simultaneous bilateral ON and myelitis related to multiple co-existing paraneoplastic antibodies (Abs), in the setting of small cell lung cancer (SCLC).
Objectives
To describe a patient with concomitant bilateral ON and myelitis as revealing neurological manifestations of paraneoplastic autoimmunity.
Methods
A 70-year-old man with a 50-pack-year smoking history was admitted because of subacute bilateral and painless vision loss and left lower limb weakness. Visual acuity was 7/10 in the right eye and 3/10 in the left eye. Fundoscopy showed bilateral disc swelling and peripapillary hemorrhages. Brain MRI did not reveal any optic nerve lesion nor lesions suggestive of MS. Spinal cord MRI showed a T2-weighted hyperintensity at the C2 level, with gadolinium enhancement. The visual evoked potentials showed significant bilateral increase of P100 latencies. CSF analysis showed lymphocytic pleocytosis (149 cells/μl), elevated protein concentration (99 mg/dl), and positive CSF-restricted IgG oligoclonal bands. No malignant cells were found in the CSF. Immunologic and infectious workup was unremarkable. Testing for anti-AQP4 and -MOG Abs was negative. Lung cancer was highly suspected on whole body FDG-PET. Transbronchial needle aspiration of hilar lymph nodes revealed SCLC.
Results
The paraneoplastic antibody panel showed a significant signal for anti-Hu Abs in the serum (EUROLINE Neuronal Antigen Profile blots, EUROIMMUN), confirming the diagnosis of PNS. Anti-CV2/CRMP5 and -amphiphysin Abs were also detected, albeit at lower levels. Treatment with intravenous methylprednisolone and plasma exchange resulted in poor clinical improvement. A second malignancy (prostate cancer) was highly suspected but the patient elected to withdraw from further evaluation or treatment and received palliative care at home.
Conclusions
Simultaneous involvement of optic nerves and spinal cord is a rare manifestation of PNS. This presentation should prompt screening for a panel of onconeuronal Abs and for an underlying malignancy, particularly in older adult smokers who are unlikely to have MS or NMOSD.