Dealing with Neuropathy in Plasma-Cell Dyscrasias

Abstract

Peripheral neuropathy (PN) is a frequent complication of plasma-cell dyscrasias such as monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenströ m's disease, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, Castleman's disease, and light-chain amyloidosis. PN can be associated with the underlying disease or it can related to the treatment. The novel immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib have changed the standard treatment of multiple myeloma. Treatment-related PN induced by thalidomide (TiPN) or bortezomib (BiPN) has become the most frequent cause of symptomatic polyneuropathy in multiple myeloma and related diseases. Dealing with PN has become a major challenge in current clinical practice for multiple myeloma patients. This review deals with practical issues such as etiology, incidence, symptoms, and clinical management of treatment-emergent PN. The major focus of the hematologist should be on the prevention of PN, primarily by frequent monitoring of the patient and by timely and adequate dose reduction of thalidomide and bortezomib. Thalidomide should not be given for periods longer than 18 months, and if it is, then patients should be carefully monitored with a low threshold for discontinuation in the face of any emergent neuropathy. In the case of BiPN, the dose of bortezomib should be reduced and/or the administration interval should be prolonged from biweekly to weekly. Adequate pain management and supportive care require a multidisciplinary approach involving the treating physician, expert nursing staff, and a neurologist as clinically indicated.

European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma

“…65 Peripheral neuropathy (PNP) is an important toxicity of both thalidomide and bortezomib occurring in approximately 50% of patients. 74 PNP from thalidomide is cumulative, dose dependent and usually permanent. Bortezomib neuropathy is related to dose, schedule and mode of administration and is mostly reversible.…”

Study of Neurological Manifestations in Hematolymphoid Neoplasms in A Tertiary Care Hospital In Eastern India

“…53.8% patients with myeloma had length dependant axonal neuropathy during/after therapy. Sonneveld P et al described that up to 50% of patients with plasma-cell dyscrasia having peripheral neuropathy [6] . This study result is similar to our findings.…”

Multiple Myeloma: Supportive Care Requirements and Coordination of Patient-Centered Care

“…31 Peripheral neuropathy, defined as damage to or degeneration of peripheral nerves, affects both sensory and motor pathways and can occur as a disease-and treatment-related complication in multiple myeloma; it usually presents as numbness, weakness, or burning pain. 32 The reported incidence is 1%-20% in untreated patients and 35%-83% in patients treated for multiple myeloma. 33 The severity of the neuropathy ranges from mild to debilitating and has a substantial impact on patient quality of life.…”

“…33 Few data exist to guide pharmacologic pain management in patients with multiple myeloma who have peripheral neuropathy, and most recommendations are based on case reports, personal experience, or application of clinical experience from other disease states (e.g., diabetic neuropathy). 32 Recommended first-line agents include anticonvulsants (e.g., gabapentin, pregabalin) and antidepressants (e.g., nortriptyline, amitriptyline). 32 Opioid analgesics and tramadol are recommended as second-line agents and antiepileptics and ketamine as third-line therapies.…”

“…33 Disease-related neuropathy occurs secondary to the multiple myeloma disease process or can be the result of compression of nerve roots. 32 Risk factors for treatmentrelated peripheral neuropathy include duration of therapy, dose intensity, cumulative dose, and the presence of pre-existing neuropathy. 33 Comorbid conditions such as diabetes can also predispose patients with multiple myeloma to peripheral carinii pneumonia, herpes, and fungal infections.…”