Brentuximab Associated Guillain-Barré Syndrome (BV-GBS): Case Series and a Review of Pharmacovigilance FDA Adverse Reporting System (FAERS)
Authors: Pradeep Roshini , Benekli Zeynep Nazli , Nair Ranjit , Malpica Luis , Lee Hun Ju , Maples Eguono , Carlson Samantha , Fayad Luis E. , Ahmed Sairah , Iyer Swami P. 
Published: December 2024

Introduction:
Guillain-Barré Syndrome (GBS) is a rare neurological disorder characterized by the rapid onset of muscle weakness, altered sensation, and diminished reflexes. Early medical intervention is crucial to prevent severe complications such as respiratory failure. Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin E. While BV is primarily used in the treatment of certain types of lymphomas, it has notable neurological side effects, most commonly distal sensory-predominant axonal neuropathy (BV-N). However, the association between BV and the development of GBS has not yet been clearly defined. This gap in the literature prompted our investigation to understand the potential link between BV treatment and who may be at risk for GBS (BV-GBS).
Methods:
Out of 500 patients (pts) who received Brentuximab at MD Anderson Cancer Center, we identified 3 pts diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) following treatment with BV. We reviewed medical records, supporting studies, and treatment protocols. The FDA Adverse Event Reporting System (FAERS) was queried to retrospectively identify all instances where BV was used, specifically seeking cases with GBS (BV-GBS) and non-GBS neuropathy (BV-N). Detailed individual case reviews were performed to classify the neuropathic presentations into sensory, motor, or other neurological categories. Comparisons were made between the identified cases and the broader dataset from the FAERS database to assess potential patterns and correlations. Descriptive statistics were used to summarize and compare the clinical characteristics and outcomes of the patients.
Results:
The first patient was an 87-year-old male with peripheral T-cell lymphoma on Brentuximab maintenance therapy experienced progressive weakness in his right hand and calf, leading to difficulty walking. Diagnosed with CIDP via EMG and lumbar puncture, he improved after 2 cycles of IVIG. The second was a 50-year-old male with angioimmunoblastic T-cell lymphoma treated with CHEP-BV achieved complete resolution but developed worsening leg and fingertip numbness five months later. EMG confirmed CIDP, and symptoms improved after 5 cycles of IVIG. Finally, a 72-year-old female with multiple sclerosis and peripheral neuropathy on Brentuximab for newly diagnosed T-cell lymphoma experienced worsening sensory symptoms and leg weakness. EMG confirmed CIDP, and her symptoms improved after discontinuing Brentuximab and 5 cycles of IVIG.
The FAERS data showed that 1,582 patients developed polyneuropathy after using BV. Among these patients, 48 (3.03%) were diagnosed with BV-GBS. The study population included 30 males and 11 females, with diagnoses of 35 Hodgkin and 13 non-Hodgkin lymphomas, distributed as follows: 1 ≤20 years, 24 between 21-40, 2 between 41-60, 5 &gt;60 years (16 unspecified). All of them were deemed serious. The remaining 96.9% experienced BV-N, indicating a broad spectrum of nerve damage associated with BV. Motor symptoms, including muscle weakness, cramps, and loss of muscle control (hypotonia, areflexia), were noted in 832 patients (52.5%). Fifty-four percent experienced sensory symptoms such as tingling, numbness (hypoesthesia), and pain, often described as a burning or prickling sensation. The relative odds ratio (ROR) for BV-GBS is approximately 28.13 (p&lt;0.00001), indicating a significantly higher risk compared to those not exposed to BV.
Conclusion:
We present our experience with BV-associated GBS as well as other reported patients based on the largest dataset available, FAERS. Although rare, GBS is a very severe and generally overlooked side effect of BV therapy. It is generally characterized by a higher incidence of muscle weakness, gait disorders, and an acute or subacute onset of symptoms compared to BV-GBS. Additionally, BV-GBS can exhibit more severe neuropathy, with grade ≥3, while none of the BV-N cases reach this level of severity. Data from the FDA Adverse Event Reporting System (FAERS) highlights the need for early detection and tailored management of BV-GBS and BV-N. Early recognition of symptoms like muscle weakness and gait disorders, along with prompt clinical evaluations and interventions such as IVIG, is crucial for reducing morbidity and improving outcomes in patients receiving BV therapy for CD30+ lymphoma.