Bortezomib‐induced peripheral neuropathy is related to altered levels of brain‐derived neurotrophic factor in the peripheral blood of patients with multiple myeloma

Azoulay, David; Lavie, David; Horowitz, Netanel A.; Suriu, Celia; Gatt, Moshe E.; Akria, Luiza; Perlman, Riki; Braester, Andrei; Ben‐Yehuda, Dina

doi:10.1111/bjh.12624

Cited by 31 publications

(21 citation statements)

References 10 publications

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“…Vincristine is a chemotherapeutic agent that is associated with chemotherapy‐induced peripheral neuropathy (CIPN) (Legha, ), although the reason why some patients are more vulnerable to CIPN than others remains unclear. Our preliminary studies, showing a possible link between CIPN and blood levels of brain‐derived neurotrophic factor (BDNF) (Azoulay et al , ), point to BDNF as a potential biomarker for CIPN. The current study explored the effects of serum BDNF and the BDNF ‐Val66Met, a single nucleotide polymorphism (SNP) causing deficit in cellular distribution and secretion of BDNF in the neuronal cells (Egan et al , ) of patients with non‐Hodgkin lymphoma (NHL) who develop CIPN.…”

Section: Patient Characteristicsmentioning

confidence: 97%

Brain derived neurotropic factor single nucleotide polymorphism Val66Met and serum protein levels are associated with development of vincristine‐induced peripheral neuropathy in patients with lymphoma

et al. 2018

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Section: Patient Characteristicsmentioning

confidence: 97%

Brain derived neurotropic factor single nucleotide polymorphism Val66Met and serum protein levels are associated with development of vincristine‐induced peripheral neuropathy in patients with lymphoma

et al. 2018

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“…Another pathway possibly involved in BIPN is NF‐kB; this pathway is relevant in MM pathogenesis and there is evidence of its inhibition as a consequence of BTZ administration . NF‐kB inhibition could be responsible for a reduction in nerve growth factor and brain‐derived growth factor (BDNF), thus leading to altered neuronal survival . Other authors offered observations of another possible intracellular target for BIPN: tubulin, affected in consequence of proteasome inhibition.…”

Section: Pathogenesismentioning

confidence: 99%

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Velasco

Alberti

Bruna

et al. 2019

J Peripheral Nervous Sys

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Proteasome inhibitors (PIs), especially bortezomib (BTZ), have come to the forefront over the last years because of their unprecedented efficacy mainly against multiple myeloma (MM). Unfortunately, peripheral neuropathy (PN) secondary to treatment of MM with PIs has emerged as a clinically relevant complication, which negatively impacts the quality of life of MM survivors. Bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, which develops in 30% to 60% of patients during treatment. Typically, BIPN is a length-dependent sensory axonopathy characterized by numbness, tingling, and severe neuropathic pain in stocking and glove distribution. BIPN mechanisms have not yet been fully elucidated. Experimental studies suggest that aggresome formation, endoplasmic reticulum stress, myotoxicity, microtubule stabilization, inflammatory response, and DNA damage could contribute to this neurotoxicity. A new generation of structurally distinct PIs has been developed, being increasingly used in clinical settings. Carfilzomib exhibits a much lower neurotoxicity profile, with a significantly lower incidence of PN compared to BTZ. Pre-existing PN increases the risk of developing BIPN. Besides, BIPN is related to dose, schedule and mode of administration and modifications of these factors have lowered the incidence of PN. However, to date there is no cure for PIs-induced PN (PIIPN), and a careful neurological monitoring and dose adjustment is a key strategy for preserving quality of life. This review critically looks at the pathogenesis, incidence, risk factors, both clinical and pharmacogenetics, clinical phenotype and management of PIIPN. We also make recommendations for further elucidating the whole clinical spectrum of PIIPN. K E Y W O R D S bortezomib, carfilzomib, peripheral neuropathy, peripheral neurotoxicity, proteasome inhibitor-induced neuropathy 1 | INTRODUCTION Inhibition of proteasome function has emerged as an efficacious strategy with a robust rationale in anticancer therapy. Proteasome inhibitor (PI)-based regimens have become an integral component of the treatment of multiple myeloma (MM), a malignancy of plasma cells accounting for approximately 1% of cancers and 12% of hematological malignancies. Bortezomib (BTZ) was the first approved PI and to date has become the standard of anti-myeloma 1 and mantle cell lymphoma therapies. 2 Postmarketing trials of BTZ quickly pointed to PN as its main nonhematological, dose-limiting toxicity of BTZ. Similar to clinical trial results, the use of BTZ in real-world oncology practice documented that BTZ-induced peripheral neuropathy (BIPN) develops in up to 50% of BTZ-treated MM patients. 3,4 PN due to MM treatment

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“…However, concomitant or prior treatment with other neurotoxic drugs, such as vincristine and thalidomide, are risk factors favoring higher percentages and more serious clinical grades of toxicity. Direct damage to the dorsal root ganglion is likely to be the key target in BiPN, although mitochondrial and endoplasmic reticulum damage, deregulation of Ca 2 + homeostasis, inhibition of transcription of nerve growth factor, microtubule stabilization, and autoimmune or inflammatory factors may contribute to this problem …”

Section: Introductionmentioning

confidence: 99%

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array

García‐Sanz

Corchete

Alcoceba

et al. 2016

Hematological Oncology

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Bortezomib‐ and thalidomide‐based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment‐induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome‐wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest‐ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment.

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Bortezomib‐induced peripheral neuropathy is related to altered levels of brain‐derived neurotrophic factor in the peripheral blood of patients with multiple myeloma

Cited by 31 publications

References 10 publications

Brain derived neurotropic factor single nucleotide polymorphism Val66Met and serum protein levels are associated with development of vincristine‐induced peripheral neuropathy in patients with lymphoma

Brain derived neurotropic factor single nucleotide polymorphism Val66Met and serum protein levels are associated with development of vincristine‐induced peripheral neuropathy in patients with lymphoma

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array

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