microRNAs as the biomarkers of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma

Łuczkowska, Karolina; Rogińska, Dorota; Ulańczyk, Zofia; Safranow, Krzysztof; Paczkowska, Edyta; Baumert, Bartłomiej; Milczarek, Sławomir; Osękowska, Bogumiła; Górska, Martyna; Borowiecka, Ewa; Sommerfeld, Krzysztof; Zawodny, Piotr; Szudy‐Szczyrek, Aneta; Hus, Marek; Machaliński, Bogusław

doi:10.1080/10428194.2021.1933478

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…This result was consistent with previous studies using sequential treatment [7,8]. Subcutaneous injection (SC) and the once-weekly schedule of bortezomib in our study may be the reason for the significantly lower rates of peripheral neuropathy, which was also reported in several studies [8,[14][15][16], and most importantly, the efficacy of SC is not compromised compared with IV administration [17]. Additionally, Toor et al [18] reported that grade III/ IV peripheral neuropathy (PN) was more associated with the Vd and IMiD combination group (15.7%) than the VCd group, in which no grade III/IV PN was noted.…”

Section: Discussionsupporting

confidence: 93%

Efficacy and safety analysis of bortezomib-based triplet regimens sequential lenalidomide in newly diagnosed multiple myeloma patients

Zhou

Wen

et al. 2022

Clin Exp Med

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The aim of this study is to analyze the efficacy and safety of sequential therapy with bortezomib-based triplet regimens without lenalidomide (PXD, including VTD, PAD, and VCD) followed by continuous lenalidomide and dexamethasone (Rd) or bortezomib and dexamethasone (Vd) treatment. The main objective is to evaluate the advantages of PXD followed by Rd compared to the combinations of bortezomib–lenalidomide–dexamethasone (VRd) in newly diagnosed multiple myeloma (NDMM). Fifty-eight nontransplant NDMM patients who were admitted to our department from 2017 to 2019 were included in this study. Bortezomib-based triplet regimens were initially selected and followed by Rd or Vd as continuous treatment once the patients achieved partial remission (PR) or better response. The efficacy and safety of the patients were observed. The Rd continuous treatment cohort was compared with historical data from the EVOLUTION trial on continuous VRd treatment. In our cohort, the overall survival rate was 100%, and progression-free survival (PFS) was 38.5% after a median of 19 (4–36) cycles of Rd continuous therapy was applied. During the follow-up period, the best outcome assessments achieved were 53.8% complete response (CR) and 84.6% excellent partial response (VGPR). A total of 23.1% had grade 3–4 or higher drug-related adverse reactions, mainly hematological toxicity, and no patients died of adverse reactions. Compared with the Vd group, the Rd group had a better PFS and VGPR rate (2-year PFS: 92.3% vs. 56.3%, P = 0.002; 3-year PFS: 69.2% vs. 8.0%, P < 0.001; VGPR: 84.6% vs. 69.2%, P = 0.02). No significant differences were found in ORR (100% vs. 92.3%) or CR (53.8% vs. 35.7%, P = 0.082). Compared with the EVOLUTION study, patients in the Rd group had a more advanced disease stage (stage III rate of 40% vs. 19%, P = 0.039) and worse physical status (KPS 50–60 rate of 25.0% vs. 2.0%, P = 0.000). However, a higher proportion of ORR (100% vs. 73.0%, P < 0.001), VGPR or better (75.0% vs. 32.0%, P < 0.001), and PFS at 12 months (90.0% vs. 68%, P = 0.011) were achieved. Sequential administration of bortezomib-based triplet regimens without lenalidomide as an initial therapy followed by Rd as a continuous treatment may not be inferior to VRd for first-line treatment in NDMM patients.

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Section: Discussionsupporting

confidence: 93%

Efficacy and safety analysis of bortezomib-based triplet regimens sequential lenalidomide in newly diagnosed multiple myeloma patients

Zhou

Wen

et al. 2022

Clin Exp Med

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“…Blocking miR-155 expression reduced mechanical allodynia and thermal hyperalgesia in rats [ 39 ]. In our previous study [ 40 ], we showed the relationship between changes in plasma miRNA expression (miR-22-3p; miR-23a-3p; miR-24-3p) in patients with MM with the development of drug-induced peripheral neuropathy. These studies confirmed that the treatment affects epigenetic modification and may be related to the development of neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib-Induced Epigenetic Alterations in Nerve Cells: Focus on the Mechanisms Contributing to the Peripheral Neuropathy Development

Łuczkowska

Rogińska

Kulig

et al. 2022

IJMS

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Bortezomib-induced peripheral neuropathy (BiPN) occurs in approximately 40% of patients with multiple myeloma. The induction of severe neuropathy entails the dose reduction or complete elimination of bortezomib (BTZ). Interestingly, discontinuation of BTZ mostly results in a reduction or complete resolution of peripheral neuropathy (PN) symptoms. Therefore, it is likely that the BiPN mechanisms are based on temporary/reversible changes such as epigenetic alterations. In this study, we examined the effect of treating nerve cells, differentiated from the Lund human mesencephalic (dLUHMES) cell line, with several low-dose BTZ (0.15 nM) applications. We showed a significant decrease in global histone H3 acetylation as well as histone H3 lysine 9 acetylation. Moreover, analysis of the genetic microarray showed changes mainly in epigenetic processes related to chromatin rearrangement, chromatin silencing, and gene silencing. GSEA analysis revealed three interesting signaling pathways (SIRT1, B-WICH and, b-Catenin) that may play a pivotal role in PN development. We also performed an analysis of the miRNA microarray which showed the interactions of miR-6810-5p with the genes MSN, FOXM1, TSPAN9, and SLC1A5, which are directly involved in neuroprotective processes, neuronal differentiation, and signal transduction. The study confirmed the existence of BTZ-induced complex epigenetic alterations in nerve cells. However, further studies are necessary to assess the reversibility of epigenetic changes and their potential impact on the induction/resolution of PN.

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“…9 Pregabalin and gabapentin are also used to prevent peripheral neuropathy in MM patients. 10 However, there are no evidence-based therapies to prevent chemotherapy-induced peripheral neuropathy. Varicella zoster virus vaccine has been documented to reduce the incidence of HZ and PHN in MM patients.…”

Section: Discussionmentioning

confidence: 99%

Refractory postherpetic neuralgia in a multiple myeloma patient with lenalidomide maintenance therapy: a case report

Cao

Jiao

et al. 2022

J Int Med Res

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Herpes zoster is not common in multiple myeloma (MM) patients treated with lenalidomide-based regimens. We report an MM patient in his late 60s who received lenalidomide as maintenance treatment and whose condition was complicated with refractory postherpetic neuralgia. The patient received antiviral treatment and analgesia immediately after the diagnosis of herpes zoster. Two months later, the patient received acupuncture, radiofrequency treatment, and even spinal cord stimulation, which failed to relieve the pain. Consequently, we performed high-resolution magnetic resonance imaging of the cervical and thoracic nerves. Then, stellate ganglion block, left C5/C6/C7/C8 nerve root block, and left thoracic 1, 2 paravertebral nerve block were performed with the assistance of real-time ultrasound. The pain was immediately relieved after treatment; however, the symptoms reappeared 2 days later. At 5 months after treatment, the patient still experienced severe pain. We suggest that MM patients complicated with postherpetic neuralgia are refractory to treatment. Starting nerve block therapy, pulsed radiofrequency, and other interventional therapies as early as possible could be a more optimal treatment plan for these patients.

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microRNAs as the biomarkers of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma

Cited by 10 publications

References 42 publications

Efficacy and safety analysis of bortezomib-based triplet regimens sequential lenalidomide in newly diagnosed multiple myeloma patients

Efficacy and safety analysis of bortezomib-based triplet regimens sequential lenalidomide in newly diagnosed multiple myeloma patients

Bortezomib-Induced Epigenetic Alterations in Nerve Cells: Focus on the Mechanisms Contributing to the Peripheral Neuropathy Development

Refractory postherpetic neuralgia in a multiple myeloma patient with lenalidomide maintenance therapy: a case report

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