Management of treatment-emergent peripheral neuropathy in multiple myeloma

Abstract

Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions.

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

“…20 The incidence of peripheral neuropathy was 27% in the ixazomib group (15% had grade 1 events and 10%, grade 2 events) and 22% in the placebo group (14% had grade 1 events and 6%, grade 2 events); 2% of patients in each study group had grade 3 events, and no grade 4 or 5 events or serious adverse events of peripheral neuropathy were reported. The incidence of peripheral neuropathy with pain was 4% in the ixazomib group and 3% in the placebo group.…”

Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma

“…24,25 The introduction of subcutaneous administration has improved convenience compared with the intravenous approach and substantially reduced the risk of peripheral neuropathy (PN), 26 a major limiting factor for long-term administration. 27 Other studies have shown that once-weekly administration of bortezomib can significantly reduce the risk of PN while preserving efficacy. 28,29 Given this context, the development of an orally bioavailable PI with an improved toxicity profile would represent a major advance for MM therapy.…”

Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network

“…53 There are clear guidelines for the treatment of BiPNP (Table 3). 54 In case of BiPNP grade 1 with pain or grade 2, the bortezomib dose should be reduced to 1.0 mg/m 2 twice weekly or the treatment interval should be extended to 1.3 mg/m 2 once per week. In case of grade 2 with pain or grade 3 BiPNP treatment should be withheld until symptoms have resolved, then treatment can be re-initiated at a dose of 0.7 mg/m 2 once per week.…”

“…53 (Table 3). 10,13,54 Recommendations include patient monitoring at a monthly interval for the first 3 months of treatment to detect early signs of TiPNP and to continue regular monitoring during the entire treatment duration.…”

“…3,4,8 Other agents, such as acetyl-L-carnitine and alphalipoic acid have shown activity in treatment of chemotherapy-emergent PNP of other cancers. 54 In case of neuropathic pain the three-step ladder of pain management in cancer patients issued by the World…”