Prevention of Bortezomib-Induced Polyneuropathy in Multiple Myeloma Patients
DOI:
https://doi.org/10.12974/2312-5411.2020.07.3Keywords:
Bortezomib, Multiple myeloma, Peripheral neuropathy.Abstract
Bortezomib (Velcade®) is a proteasome pathway inhibitor that has improved multiple myeloma (MM) overall survival. Bortezomib-induced peripheral neuropathy (BIPN) is a frequent adverse event, requiring delay, dose reduction or cessation of therapy. Although most of the symptoms resolve after discontinuation or dose-reduction, almost 25% develop chronic symptoms, affecting quality of life and limiting the therapeutic choices.
There is limited evidence regarding the strategies to prevent bortezomib-induced polyneuropathy (BIPN). We conducted a review of the published data to summarize the available information regarding BIPN prevention strategies.
Our search included literature published in the Cochrane Library databases, Medline/PubMed, SciELO, Google Scholar, and Trip Database in the last ten years, including observational analytic studies, experimental studies, systematic reviews, and metanalysis, which reported the efficacy of interventions to prevent BIPN.
Eight studies have been included. The subcutaneous administration of bortezomib has shown a protective effect of all grades of BIPN (OR=0.40, 95% CI 0.27 to 0.59, p<0.001) and grade 3 to 4 (OR = 0.45, 95% CI 0.25 to 0.82, P<0.05), as evidenced in a metanalysis. Cumulative dose of bortezomib > 30 mg/m2 is significantly associated with a higher risk of BIPN.
Other therapies as Acetyl-l-carnitine (ALC), dexamethasone in partnered dosing (day of/after bortezomib), high-dose intravenous mecobalamin (HDIME), and the combination of docosahexaenoic acid, α-lipoic acid, vitamin C 60 mg, and vitamin E have been assessed but their efficacy for BIPN prevention has not been confirmed.
We conclude that the subcutaneous route of administration of bortezomib effectively prevents BIPN while other strategies lack robust evidence to be recommended.
References
Robak P, Robak T. Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later. Drugs R D. 2019; 19(2): 73-92. https://doi.org/10.1007/s40268-019-0269-9
Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification, and management. Am J Hematol. 2020 May; 95(5): 548-567. https://doi.org/10.1002/ajh.25791
Meregalli C. An Overview of Bortezomib-Induced Neurotoxicity. Toxics. 2015; 3(3): 294-303. Published 2015 Jul 27. https://doi.org/10.3390/toxics3030294
Boyette-Davis JA, Cata JP, Zhang H, et al. Follow-up psychophysical studies in bortezomib-related chemoneuropathy patients. J Pain. 2011; 12(9): 1017-1024. https://doi.org/10.1016/j.jpain.2011.04.008
Kumar SK, Laubach JP, Giove TJ, Quick M, Neuwirth R, Yung G, et al. Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. Br J Haematol. 2017; 178(5): 756-763 (PubMED). https://doi.org/10.1111/bjh.14754
Sidana S, Narkhede M, Elson P, Hastings D, Faiman B, Valent J, et al. neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis. PLoS One. 2017; 12(3): e0172996. (Trip) https://doi.org/10.1371/journal.pone.0172996
Liu H, Xu R, Huang H. Peripheral neuropathy outcomes and efficacy of subcutaneous bortezomib when combined with thalidomide and dexamethasone in the treatment of multiple myeloma. Exp Ther Med. 2016 Nov; 12(5): 3041-3046 (Trip). https://doi.org/10.3892/etm.2016.3738
Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study, The Lancet Oncology 2011; 12(5): 431-440. (Trip) https://doi.org/10.1016/S1470-2045(11)70081-X
Wang L, Wang KF, Chang BY, Chen XQ, Xia ZJ. Onceweekly Subcutaneous Administration of Bortezomib in Patients with Multiple Myeloma. Asian Pacific Journal of Cancer Prevention
[Internet]. 2015 Mar 18; 16(5): 2093-8. https://doi.org/10.7314/APJCP.2015.16.5.2093
Cavaletti G, Jakubowiak AJ. Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies. Leuk Lymphoma. 2010; 51(7): 1178-87. https://doi.org/10.3109/10428194.2010.483303
Callander N, Markovina S, Eickhoff J, Hutson P, Campbell T, Hematti P, et al. Acetyl-L-carnitine (ALCAR) for the prevention of chemotherapy-induced peripheral neuropathy in patients with relapsed or refractory multiple myeloma treated with bortezomib, doxorubicin and low-dose dexamethasone: a study from the Wisconsin Oncology Network. Cancer Chemother Pharmacol. 2014; 74(4): 875- 882. (PubMED). https://doi.org/10.1007/s00280-014-2550-5
Zhang LL, Wang YH, Shao ZH, Ma J.
[Prophylaxis of Bortezomib-Induced Peripheral Neuropathy in Patients with Multiple Myeloma by High-Dose Intravenous Mecobalamin]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017; 25(2): 480- 484. (PubMED)
Maschio M, Zarabla A, Maialetti A, Marchesi F, Giannarelli, Gumenyuk S, et al. Prevention of Bortezomib-Related Peripheral Neuropathy With Docosahexaenoic Acid and α - Lipoic Acid in Patients With Multiple Myeloma: Preliminary Data. Integr Cancer Ther. 2018; 17(4): 1115-1124. (Trip). https://doi.org/10.1177/1534735418803758
Chaves-Moreira MM, Bezerra Rodrigues A, Peres de Oliveira P, Freire de Aguiar MI, Holanda da Cunha G, Cunha Pinto RM, et al. Peripheral neuropathy in people with multiple myeloma. Acta paul. Enferm. 2018; 31(4): 439-445. https://doi.org/10.1590/1982-0194201800061
Li T, Timmins HC, King T, Kiernan MC, Goldstein D, Park SB. Characteristics and risk factors of bortezomib induced peripheral neuropathy: A systematic review of phase III trials. Hematol Oncol. 2020; 38(3): 229-243. https://doi.org/10.1002/hon.2706
Ye Z, Chen J, Xuan Z, Yang W, Chen J. Subcutaneous bortezomib might be standard of care for patients with multiple myeloma: a systematic review and meta-analysis. Drug Des Devel Ther. 2019; 13: 1707-1716. https://doi.org/10.2147/DDDT.S198117
Xu J, Wang W, Zhong XX, Feng Y, Wei X, Liu XG. EXPRESS: Methylcobalamin ameliorates neuropathic pain induced by vincristine in rats: Effect on loss of peripheral nerve fibers and imbalance of cytokines in the spinal dorsal horn. Mol Pain. 2016; 12: 1744806916657089. https://doi.org/10.1177/1744806916657089
Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, et al. American Society of Clinical Oncology. Prevention and management of chemotherapyinduced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014; 32(18): 1941-67. https://doi.org/10.1200/JCO.2013.54.0914
