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.
To describe a case of non-carryover obinutuzumab PML occuring in a female patient with chronic lymphocytic leukemia.
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.
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.
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.