Baseline peripheral neuropathy was associated with age and a prognostic factor in newly diagnosed multiple myeloma patients

Dong, Mengmeng; Zhang, Jinna; Han, Xiaoyan; He, Jingsong; Zheng, Gaofeng; Zhang, Cai

doi:10.1038/s41598-022-13935-2

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…However, we and others have previously reported that spinal microglial reaction in cancer-induced bone pain models is a highly variable occurrence that may not reflect the clinical reality (43,44). Instead, the neuropathic component of MIBP is in line with clinical reports describing baseline peripheral neuropathy in a proportion of MM patients (45,46), which is also used as a prognostic factor of chemotherapy induced peripheral neuropathy and treatment outcome in this patient population (47). These results, in combination with our observation of periosteal nerve sprouting, suggest that medications targeted to neuropathic pain patients may be useful to treat a fraction of myeloma bone pain patients.…”

Section: Discussionsupporting

confidence: 71%

Metastatic infiltration of nervous tissue and periosteal nerve sprouting in multiple myeloma induced bone pain

Diaz‐delCastillo

Palasca

Nemler

et al. 2022

Preprint

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Multiple myeloma (MM) is a neoplasia of B plasma cells that often induces bone pain. However, the mechanisms underlying myeloma-induced bone pain (MIBP) are mostly unknown. Using a syngeneic MM mouse model, we show that periosteal nerve sprouting of calcitonin-gene related protein (CGRP+) and growth associated protein 43 (GAP43+) fibres occurs concurrent to the onset of nociception and its blockade provides transient pain relief. MM patient samples also showed increased periosteal innervation. Mechanistically, we investigated MM induced gene expression changes in the dorsal root ganglia (DRG) innervating the MM-bearing bone and found alterations in pathways associated with cell cycle, immune response and neuronal signalling. The MM transcriptional signature was consistent with metastatic MM infiltration to the DRG, a never-before described feature of the disease that we further demonstrated histologically. In the DRG, MM cells caused loss of vascularization and neuronal injury, which may contribute to late-stage MIBP. Interestingly, the transcriptional signature of a MM patient was consistent with MM cell infiltration to the DRG. Overall, our results suggest that MM induces a plethora of peripheral nervous system alterations that may contribute to the failure of current analgesics and suggest neuroprotective drugs as appropriate strategies to treat early onset MIBP.

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Section: Discussionsupporting

confidence: 71%

Metastatic infiltration of nervous tissue and periosteal nerve sprouting in multiple myeloma induced bone pain

Diaz‐delCastillo

Palasca

Nemler

et al. 2022

Preprint

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“…In MM, many prognostic and predictive biomarkers are of high value in predicting therapeutic efficacy, as well as indicating PFS and OS. Translocations, copy number abnormalities and mutations at the gene level, minimal residual disease (MRD) measured by flow cytometry and next-generation sequencing (NGS) detection, blood biopsy detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and baseline clinical characters have gradually become advanced biomarkers ( 31 – 33 ). However, these indicators are still not perfect, and certain examinations are invasive or costly.…”

Section: Discussionmentioning

confidence: 99%

High serum IL-17A is associated with bone destruction in newly diagnosed multiple myeloma patients

et al. 2022

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BackgroundMultiple myeloma (MM) is a malignant proliferative disease of the blood system, characterized by the abnormal growth of clonal plasma cells in the bone marrow. The bone marrow microenvironment (BMM) is highly critical in the pathological process of MM. Many studies have shown that serum interleukin-17A (IL-17A) plays a key role in various infectious diseases, autoimmune diseases, and cancers. However, more clinical studies need to be performed to further prove the influence of serum IL-17A levels on multiple myeloma patients.MethodsAmong a total of 357 participants in our institution’s MM cohort, 175 were eligible for the retrospective study. Multivariate regression models adjusted by potential confounding factors, the violin plots, the generalized additive model and smooth curve fittings, receiver operating characteristic (ROC) curve, and Kaplan–Meier (K-M) curve analysis were applied to the research.ResultsA total of 175 patients with newly diagnosed MM were enrolled in this study. The multivariate linear regression analysis showed that serum IL-17A level in MM patients correlated with the degree of bone lesions and fracture incidence (fully adjusted model, pbone lesion < 0.0001, pfracture < 0.0001). The violin plot showed that MM patients with higher serum IL-17A levels had more severe bone lesions and higher fracture incidence than those with lower serum IL-17A levels. A total of 171 patients were included in the study of the relationship between serum IL-17A and best overall effect (BOE). We found that serum IL-17A levels were independently related to the best inductive therapeutic efficacy (fully adjusted model, p = 0.037), and the relationship was especially obvious in the light chain group (fully adjusted model, p = 0.009) and IgA group (fully adjusted model, p = 0.0456). It could be deduced from the smooth curve that the higher the serum IL-17A level, the worse the BOE (p = 0.0163). The ROC prediction curve suggested that serum IL-17A could predict the BOE to a certain extent (area under the curve (AUC) = 0.717, p = 0.0327). A total of 148 MM patients were observed in the longitudinal study of the relationship between serum IL-17A and progression-free survival/overall survival (PFS/OS). The K-M curve analysis indicated that serum IL-17A levels in MM patients were not significantly correlated with PFS and OS. However, in the light chain subgroup, MM patients with high serum IL-17A had worse PFS (p = 0.015) and OS (p = 0.0076) compared to those with low serum IL-17A. In the IgA type subgroup, the higher IL-17A level was related to worse OS (p = 0.0061).ConclusionThis retrospective study found that higher levels of serum IL-17A were independently correlated with higher severity of bone disease and fracture incidence in newly diagnosed MM patients. High serum IL-17A level was related to poor best overall efficacy in the light chain type. High serum IL-17A was also associated with poor PFS and OS in the light chain type and OS in the IgA type subgroup.

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“… 1 Peripheral neuropathy (PN) is a common complication of MM that mainly manifests as sensory neuropathies and motor neuropathies in severe cases. 2 Multiple myeloma peripheral neuropathy (MMPN) can be divided into disease-related PN and drug-related PN. In disease-related PN, sensory modalities may be affected, resulting in axonal sensorimotor neuropathy with a length-dependent pattern of axonal regrowth.…”

Section: Introductionmentioning

confidence: 99%

Acupuncture in Multiple Myeloma Peripheral Neuropathy: A Systematic Review

Lyu,

Xiao,

Yin

et al. 2024

JPR

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Background Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN. Methods The PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched from inception to November 1, 2023 to identify relevant studies pertaining to the use of acupuncture to treat MMPN. Results A total of five studies, encompassing 97 patients diagnosed with drug-related PN, were ultimately included in this analysis. The literature lacks any reports pertaining to the utilization of acupuncture for disease-related PN. ST36, LI4, SP6, and EX-LE-10 were found to be the most frequently chosen acupoints. Following acupuncture treatment, there was a consistent reduction in scores on the Visual Analogue Scale (VAS), Neuropathic Pain Scale (NPS), Brief Pain Inventory-Short Form (BPI-SF), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) among MMPN patients. The results of Nerve Conduction Velocity (NCV) tests yielded conflicting results. No severe adverse effects were reported. Conclusion The use of acupuncture for disease-related PN has not been studied to date. Acupuncture is safe for drug-related PN and is helpful for relieving pain. But uncertainty exists regarding the efficacy of this approach because there is substantial heterogeneity with respect to acupuncture treatment regimens, and more high-quality studies on this topic are warranted.

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Baseline peripheral neuropathy was associated with age and a prognostic factor in newly diagnosed multiple myeloma patients

Cited by 4 publications

References 32 publications

Metastatic infiltration of nervous tissue and periosteal nerve sprouting in multiple myeloma induced bone pain

Metastatic infiltration of nervous tissue and periosteal nerve sprouting in multiple myeloma induced bone pain

High serum IL-17A is associated with bone destruction in newly diagnosed multiple myeloma patients

Acupuncture in Multiple Myeloma Peripheral Neuropathy: A Systematic Review

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