Acute leukoencephalopathy associated with daratumumab treatment in POEMS syndrome: a case report

Abstract

Objectives: Daratumumab, a monoclonal antibody against CD38, is increasingly used in the treatment of multiple myeloma, other hematological malignancies and autoimmune diseases. Little is known about its CNS toxicity. We present a case of a patient with POEMS syndrome (syndrome of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) who developed an acute leukoencephalopathy shortly after initiation of therapy with daratumumab.

Methods: Case report following the CARE case report guidelines.

Results: The patient presented with symptoms of headache and diffuse worsening of a pre-existing tetraparesis. MRI showed a rapidly progressive leukoencephalopathy. Extensive diagnostic evaluation revealed no specific cause, suggesting the leukoencephalopathy to be caused by daratumumab.

Discussion: Our report highlights a probably rare, but clinically significant adverse effect of daratumumab and underlines the necessity of raised vigilance for neurological side effects in patients treated with daratumumab.

Keywords: CD38-antibody; POEMS; daratumumab; rapidly progressive leukoencephalopathy; toxic leukoencephalopathy.

Figure 1

Acute progressive leukoencephalopathy shortly after initiation of therapy with daratumumab. DWI, ADC and FLAIR sequences of the initial brain MRI examination on day 0 and follow up imaging on day 3, 8 and 45. Orange arrowheads indicate new or progressive lesions. (A1-A3) Bilateral, diffuse diffusion restriction in the deep white matter of the parietal centrum semiovale with discrete FLAIR hyperintense correlate on left parietal side. (B1-C3) Progression of the bilateral and diffuse diffusion restriction with T2w and FLAIR hyperintense correlate on the left parietal side. New correlating FLAIR hyperintensities on the right parietal side. Start of pseudo-normalization of ADC in the more parietal areas (C2). (D1-D3) Further progression of the bilateral confluent FLAIR hyperintensities to the frontal white matter of centrum semiovale. Almost complete pseudonormalization of ADC with residual diffusion restriction. FLAIR, Fluid attenuated inversion recovery; DWI, Diffusion weighted imaging; ADC, Apparent diffusion coefficient.