Guillain Barré Syndrome in a multiple myeloma patient after the first course of bortezomib therapy: A case report

Abstract

Abstract. Bortezomib is approved for treating relapsed multiple myeloma (MM) and mantle cell lymphoma, and clinical evidence has shown complete clinical responses in MM patients. Peripheral neuropathy is one of the most common adverse effects of bortezomib. However, rare evidence has shown that bortezomib is associated with Guillain-Barré syndrome (GBS). In the present study, a case of GBS is reported in an MM patient finishing the first course of bortezomib therapy. Based on a bone marrow cell examination revealing 34% plasma cell infiltration and according to the International Staging System, the patient was diagnosed with stage III MM (λ type). Thus, a chemotherapy protocol was performed, which consisted of bortezomib and dexamethasone. However, 5 days after the first cycle, paresthesias of the upper and lower limbs developed. Standard nerve conduction studies revealed marked reduction of the motor conduction velocity of the median nerve bilaterally and of the right ulnar nerve, while sensory conduction was significantly slowed in the majority of the nerves of the upper and lower limbs. However, there was no evidence of demyelination. With this clinical evidence, a diagnosis of GBS was considered. The patient was subsequently treated with high-dose intravenous immunoglobulins (IVIGs; 400 mg/kg/day for 5 days). Following IVIG treatment, the symptoms were largely relieved. This study suggested that GBS may occur when administering bortezomib, and that high-dose IVIGs could treat the symptoms of GBS. IntroductionMultiple myeloma (MM) is a hematological malignancy characterized by the accumulation of monoclonal plasma cells (>10% by definition) in the bone marrow (1). Chemotherapy and autologous transplantation is the major therapeutic tool for MM. It is a slowly progressing disease with a median survival of 5 years (2).Guillain-Barré syndrome (GBS) is an autoimmune disease affecting the peripheral nervous system and is generally triggered by an acute infection. Plasma exchange or intravenous immunoglobulin, together with general supportive care has improved the outcome of GBS dramatically; the mortality in the most severe patients has fallen from 30% to 5% (3).Bortezomib, a selective, reversible proteasome inhibitor is extensively used in patients with multiple myeloma (MM), and peripheral neuropathy (PN) is one of the most common and severe side-effects. Bortezomib-induced peripheral neuropathy (BIPN) is a small-fiber sensory neuropathy that is characterized by distal symmetric loss of all modalities in the lower limbs (4).The current study presents the case of a patient with MM who developed Guillain-Barré syndrome (GBS) after the first course of bortezomib therapy. Written informed consent was obtained from the patient. Case reportA 67-year-old male with an unremarkable medical history was transferred to Jiangsu Province Hospital Affiliated to Nanjing University of Traditional Chinese Medicine (Nanjing, Jiangsu, China) in November 2013 with fatigue and unintended weight loss. The laboratory examinations at ad...

Dose-dependent immunomodulatory effects of bortezomib in experimental autoimmune neuritis

“…33 , 39 , 40 However, the appearance of neurotoxic side effects like BiPNP has restrained research on further modes of action of proteasome inhibitors. 15–17 As reported above, this toxic polyneuropathy occurs mainly when BTZ is administered frequently (1.3 mg/m² given s.c. on Days 1, 4, 8 and 11, and every 21 days thereafter for three or four cycles) in multiple myeloma patients. Our experimental setup shows for the first time that one cycle of low dose BTZ application can ameliorate clinical, electrophysiological and histological signs of neuritis.…”

“…This effect is of main clinical importance as immediate withdrawal of the drug after development of a toxic sensory neuropathy can reverse neuropathic symptoms in multiple myeloma patients with BiPNP. 15–17 Interestingly, the high concentration of BTZ did not exert any immunomodulatory effects in the flow cytometry analyses or qPCR on immune cell populations. NFKB pathway was not modulated.…”

“…BTZ is known to deplete plasma cells in patients with multiple myeloma. 12–14 Its use is, however, restricted mainly due to a bortezomib-induced polyneuropathy (BiPNP) 15–17 in the usual oncological schema [1.3 mg/m 2 given subcutaneously (s.c.)] on Days 1, 4, 8 and 11, and every 21 days thereafter for an average of four cycles in multiple myeloma. The CIDP patients in our study received one or two cycles of BTZ with 1.3 mg/m 2 given s.c. on Days 1, 4, 8 and 11, every 6–12 months, which did not lead to neurotoxic effects.…”

Blocking TRPA1 and TNF-α Signal Improves Bortezomib-Induced Neuropathic Pain

“…The difference may be due to species and/ or dosages of BTZ used in patients and animals [27,28]. Nonetheless, this prior animal study further showed that anti-TNF-α alleviated a decrease of density of myelinated fibers.…”

“…A prior human study showed no evidence of demyelination in patient treated with BTZ [27]; whereas a study using mice demonstrated a loss of myelinated fibers of peripheral sensory nerves after BTZ administration [28]. The difference may be due to species and/ or dosages of BTZ used in patients and animals [27,28].…”