Prevalence, Intensity and Consequences of Bortezomib-induced Neuropathic Disorders.

Cancer-induced peripheral neuropathies (CIPN) remain a real problem in oncology (Balayssac et al., 2011). These CIPN are induced by certain classes of anticancer drugs such as taxanes (paclitaxel and docetaxel), platinum salts (cisplatin and oxaliplatin), alkaloids of Madagascar periwinkle (vincristine), bortezomib, thalidomide and eribulin (Balayssac et al., 2011; Vahdat et al., 2013). These CIPN essentially translate into sensory disorders such as paresthesia, dysesthetics or numbness. More rarely, these CIPN may be associated with motor or vegetative disorders (Balayssac et al., 2011). According to the recent meta-analysis by Hershman et al., no treatment can be proposed as a "gold standard" for preventing or treating CIPN (Hershman et al., 2014). As a result, oncologists reduce or stop doses of neurotoxic anticancer drugs because patients with CIPN have a marked deterioration in quality of life and co-morbidities such as anxiety, depression and sleep disorders (Hong et al., 2014; Mols et al., 2014). Therefore, understanding the pathophysiology of CIPN is essential to propose new therapeutic strategies. Among neurotoxic anticancer drugs, bortezomib remains relatively little studied in terms of pathophysiology compared to platinum salts or taxanes, while the neurotoxicity of bortezomib remains a limiting factor in treatment. Since 2012, the FDA and EMA have validated the administration of bortezomib subcutaneously instead of intravenously in order to limit the neurotoxicity of bortezomib (Minarik et al., 2015). Indeed, a large study (N=222) reported that subcutaneous administration of bortezomib allowed the same therapeutic efficacy to be maintained while improving the safety profile and in particular limiting peripheral neuropathies (CIPN all grades: 38% vs. 53%, p=0.044, grade\> 2: 24% vs. 41%, p=0.012 and grade\> 3: 6% vs. 16%, p=0.026) However, a recent retrospective study (N=446) reports that the prevalence of bortezomib-induced peripheral neuropathies after subcutaneous administration remains relatively high: all grade: 41%, grade\> 2: 18%, grade\> 3: 4%, and above all that this prevalence is not different between subcutaneous and intravenous routes (Minarik et al., 2015).

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* \- Patients previously treated with bortezomib for multiple myeloma between 2008 and 2016 at Clermont-Ferrand University Hospital.
* Oral non-opposition of participation in the study

Exclusion Criteria:

* Patient unable to understand or answer questionnaires.
* Age \< 18 years.
* Neurological pathologies (e. g. Parkinson's syndrome, stroke, fibromyalgia, etc.).
* Legal incapacity (person deprived of liberty or under guardianship).

• DERIVEDGiraudet F, Selvy M, Kerckhove N, Pereira B, Barreau F, Nguyen D, Busserolles J, Cabrespine A, Chaleteix C, Soubrier M, Bay JO, Lemal R, Balayssac D. Relation between auditory difficulties and bortezomib-induced peripheral neuropathy in multiple myeloma: a single-center cross-sectional study. Eur Arch Otorhinolaryngol. 2022 Apr;279(4):2197-2201. doi: 10.1007/s00405-021-07234-1. Epub 2022 Jan 31. PMID 35098333
• DERIVEDEngelhardt M, Ihorst G, Singh M, Rieth A, Saba G, Pellan M, Lebioda A. Real-World Evaluation of Health-Related Quality of Life in Patients With Multiple Myeloma From Germany. Clin Lymphoma Myeloma Leuk. 2021 Feb;21(2):e160-e175. doi: 10.1016/j.clml.2020.10.002. Epub 2020 Oct 24. PMID 33218965