medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-238medsovet-7691Research ArticleПОДДЕРЖИВАЮЩАЯ ТЕРАПИЯSUPPORTIVE THERAPYПатофизиология и лечение болевого синдрома при множественной миеломеPathophysiology and treatment of pain in multiple myelomahttps://orcid.org/0000-0002-8129-8114СемочкинС. В.SemochkinS. V.

Семочкин Сергей Вячеславович, д.м.н., руководитель группы высокодозной химиотерапии и трансплантации костного мозга; профессор кафедры онкологии, гематологии и лучевой терапиипедиатрического факультета 

125834, Россия, Москва, 2-й Боткинский проезд, д. 3

117997, Россия, Москва, ул. Островитянова, д. 1 

Sergey V. Semochkin, Dr. Sci. (Med.), Head of High-Dose Chemotherapy and Bone Marrow Transplantation Group; Professor of the Department of Oncology, Hematology and Radiotherapy of the Pediatric Faculty

3, 2nd Botkinskiy Proezd, Moscow, 125834, Russia

1, Ostrovityanov St., Moscow, 117997, Russia 

semochkin_sv@rsmu.ruМосковский научный исследовательский онкологический институт имени П.А. Герцена – филиал Национального медицинского исследовательского центра радиологии; Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияHertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Center; Pirogov Russian National Research Medical UniversityRussian Federation2023280720230117589Copyright © Семочкин С.В., 20232023Семочкин С.В.Semochkin S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7691

Пациенты с множественной миеломой (ММ) нередко страдают от хронической боли разной степени интенсивности, возникающей на всех этапах развития болезни. Наиболее частыми проблемами в дебюте ММ являются скелетные осложнения, связанные с формированием очагов остеолизиса. Патологические переломы и компрессия спинного мозга на протяжении первой линии терапии ММ встречаются у 17 и 6% пациентов соответственно. С помощью ПЭТ/КТ и МРТ остеолитические очаги визуализируются более чем у 90% первичных пациентов. Боль в костях объясняется повышением давления в костном мозге, высвобождением опухолевыми плазматическими клетками химических медиаторов и возникновением микротрещин в костях опосредованно к нарушению локального метаболизма. Терапия болевого синдрома, связанного с поражением костей, включает противомиеломную химио- и радиотерапию, остеомодифицирующую терапию бисфосфонатами или деносумабом, вертебропластику и непосредственное фармакологическое подавление боли. Применение для лечения ММ ингибиторов протеасом и моноклональных антител ассоциируется с риском реактивации вируса простого герпеса (HSV) и вируса варицелла-зостер (VZV). Результатом заживления герпетических высыпаний у части больных будет развитие постгерпетической невралгии, проявляющейся мучительной болью на протяжении месяцев или лет. Применение ингибитора протеасом бортезомиба часто ассоциируется с развитием длительно персистирующей периферической нейропатии, часто осложненной болевым синдромом. По своим нейробиологическим и клиническим особенностям боль классифицируют на ноцицептивную, нейропатическую и функциональную. Костная боль носит ноцицептивный характер, а для постгерпетической и индуцированной химиотерапией нейропатии более значим нейропатический компонент. Для ноцицептивной боли средней и тяжелой степени препаратами выбора являются опиоиды, а для нейропатической боли чаще всего применяют адъюванты – противосудорожные средства и антидепрессанты. В представленном обзоре обобщаются сведения по патофизиологии разных вариантов болевого синдрома у пациентов с ММ, а также по современным подходам к профилактике и лечению осложнений. Обсуждаются вопросы фармакологии опиоидных анальгетиков. В завершении обзора представлены данные клинического исследования нового отечественного неопиоидного агониста опиоидных μ1-рецепторов, рассматриваемого в качестве реальной альтернативы наркотическим анальгетикам.

Most patients with multiple myeloma (MM) suffer from chronic pain of varying degrees of intensity at every stage of the natural disease process. Osteolytic bone lesions are one of the most common complications of MM. The bone disease visualized by PET/CT and MRI affects up to 90% of newly diagnosed MM patients, increasing the risk of the development of skeletal-related events. Pathological fractures and spinal cord compression occur in 17% and 6% of patients, respectively. Bone pain is explained by an increase in pressure in the bone marrow, the release of chemical mediators by myeloma plasma cells, and the occurrence of microcracks in the bones, indirectly to a violation of local metabolism. Management of myeloma bone disease includes anti-myeloma chemotherapy and radiotherapy, antiresorptive therapy with bisphosphonates or denosumab, and direct pharmacological pain correction. Patients with pathological vertebral fractures and without spinal cord compression should be considered for vertebroplasty or kyphoplasty. The use of proteasome inhibitors and monoclonal antibodies for the treatment of MM is associated with a risk of herpes simplex virus (HSV) and varicella-zoster virus (VZV) reactivation. The result of the healing of herpetic eruptions in some patients will be the development of postherpetic neuralgia, manifested by excruciating pain for months or years. Moreover, the treatment with proteasome inhibitor bortezomib is often associated with the development of long-term persistent peripheral neuropathy, often complicated by pain. According to their neurobiological and clinical features, pain is classified into nociceptive, neuropathic, and functional. Bone pain is nociceptive and for postherpetic and chemotherapy-induced neuropathy, the neuropathic component is more significant. Opioids are the drugs of choice for moderate to severe nociceptive pain, while anticonvulsants and antidepressants are the most commonly used adjuvants for neuropathic pain. This review summarizes information on the pathophysiology of various types of pain syndrome in patients with MM, as well as on modern approaches to the prevention and treatment of complications. The issues of the pharmacology of opioid analgesics are discussed. The review concludes with data from a clinical trial of a new domestic non-opioid μ1-opioid receptor agonist Tafalgin, considered a real alternative to narcotic analgesics.

множественная миеломабольопиоидынаркотические анальгетикипостгерпетическая невралгиябортезомибиндуцированная нейропатияmultiple myelomapainopioidsnarcotic analgesicsTafalginpostherpetic neuralgiabortezomib-induced neuropathyReferencesDiaz-delCastillo M., Andrews R.E., Mandal A., Andersen T.L., Chantry A.D., Heegaard A.M. Bone Pain in Multiple Myeloma (BPMM)-A Protocol for a Prospective, Longitudinal, Observational Study. Cancers (Basel). 2021;13(7):1596. https://doi.org/10.3390/cancers13071596.Diaz-delCastillo M., Andrews R.E., Mandal A., Andersen T.L., Chantry A.D., Heegaard A.M. Bone Pain in Multiple Myeloma (BPMM)-A Protocol for a Prospective, Longitudinal, Observational Study. Cancers (Basel). 2021;13(7):1596. https://doi.org/10.3390/cancers13071596.Moreau P., Attal M., Caillot D., Macro M., Karlin L., Garderet L. et al. Prospective Evaluation of Magnetic Resonance Imaging and [18F] Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study. J Clin Oncol. 2017;35(25):2911–2918. https://doi.org/10.1200/JCO.2017.72.2975.Moreau P., Attal M., Caillot D., Macro M., Karlin L., Garderet L. et al. Prospective Evaluation of Magnetic Resonance Imaging and [18F] Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study. J Clin Oncol. 2017;35(25):2911–2918. https://doi.org/10.1200/JCO.2017.72.2975.Mateos M.V., Fink L., Koneswaran N., Intorcia M., Giannopoulou C., Niepel D., Cavo M. Bone complications in patients with multiple myeloma in five European countries: a retrospective patient chart review. BMC Cancer. 2020;20(1):170. https://doi.org/10.1186/s12885-020-6596-y.Mateos M.V., Fink L., Koneswaran N., Intorcia M., Giannopoulou C., Niepel D., Cavo M. Bone complications in patients with multiple myeloma in five European countries: a retrospective patient chart review. BMC Cancer. 2020;20(1):170. https://doi.org/10.1186/s12885-020-6596-y.Nahi H., Chrobok M., Gran C., Lund J., Gruber A., Gahrton G. et al. Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma. PLoS ONE. 2019;14(2):e0211927. https://doi.org/10.1371/journal.pone.0211927.Nahi H., Chrobok M., Gran C., Lund J., Gruber A., Gahrton G. et al. Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma. PLoS ONE. 2019;14(2):e0211927. https://doi.org/10.1371/journal.pone.0211927.Chanan-Khan A., Sonneveld P., Schuster M.W., Stadtmauer E.A., Facon T., Harousseau J.L. et al. Analysis of herpes zoster events among bortezomibtreated patients in the phase III APEX study. J Clin Oncol. 2008;26(29):4784–4790. https://doi.org/10.1200/JCO.2007.14.9641.Chanan-Khan A., Sonneveld P., Schuster M.W., Stadtmauer E.A., Facon T., Harousseau J.L. et al. Analysis of herpes zoster events among bortezomibtreated patients in the phase III APEX study. J Clin Oncol. 2008;26(29):4784–4790. https://doi.org/10.1200/JCO.2007.14.9641.Vassilopoulos S., Vassilopoulos A., Kalligeros M., Shehadeh F., Mylonakis E. Cumulative Incidence and Relative Risk of Infection in Patients With Multiple Myeloma Treated With Anti-CD38 Monoclonal Antibody-Based Regimens: A Systematic Review and Meta-analysis. Open Forum Infect Dis. 2022;9(11):ofac574. https://doi.org/10.1093/ofid/ofac574.Vassilopoulos S., Vassilopoulos A., Kalligeros M., Shehadeh F., Mylonakis E. Cumulative Incidence and Relative Risk of Infection in Patients With Multiple Myeloma Treated With Anti-CD38 Monoclonal Antibody-Based Regimens: A Systematic Review and Meta-analysis. Open Forum Infect Dis. 2022;9(11):ofac574. https://doi.org/10.1093/ofid/ofac574.Семочкин С.В., Соловьев М.В., Менделеева Л.П. Профилактика и лечение бортезомибиндуцированной нейропатии у пациентов с множественной миеломой. Онкогематология. 2022;17(2):141–150. https://doi.org/10.17650/1818-8346-2022-17-2-141-150.Semochkin S.V., Solovyev M.V., Mendeleeva L.P. Prevention and management of bortezomib-induced peripheral neuropathy in patients with multiple myeloma. Oncogematologiya. 2022;17(2):141–150. (In Russ.) https://doi.org/10.17650/1818-8346-2022-17-2-141-150.Panaroni C., Yee A.J., Raje N.S. Myeloma and Bone Disease. Curr Osteoporos Rep. 2017;15(5):483–498. https://doi.org/10.1007/s11914-017-0397-5.Panaroni C., Yee A.J., Raje N.S. Myeloma and Bone Disease. Curr Osteoporos Rep. 2017;15(5):483–498. https://doi.org/10.1007/s11914-017-0397-5.Kim J.M., Lin C., Stavre Z., Greenblatt M.B., Shim J.H. Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells. 2020;9(9):2073. https://doi.org/10.3390/cells9092073.Kim J.M., Lin C., Stavre Z., Greenblatt M.B., Shim J.H. Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells. 2020;9(9):2073. https://doi.org/10.3390/cells9092073.Nencini S., Ivanusic J.J. The Physiology of Bone Pain. How Much Do We Really Know? Front Physiol. 2016;7:157. https://doi.org/10.3389/fphys.2016.00157.Nencini S., Ivanusic J.J. The Physiology of Bone Pain. How Much Do We Really Know? Front Physiol. 2016;7:157. https://doi.org/10.3389/fphys.2016.00157.Yoneda T., Hiasa M., Okui T. Crosstalk Between Sensory Nerves and Cancer in Bone. Curr Osteoporos Rep. 2018;16(6):648–656. https://doi.org/10.1007/s11914-018-0489-x.Yoneda T., Hiasa M., Okui T. Crosstalk Between Sensory Nerves and Cancer in Bone. Curr Osteoporos Rep. 2018;16(6):648–656. https://doi.org/10.1007/s11914-018-0489-x.Choi S.J., Oba Y., Gazitt Y., Alsina M., Cruz J., Anderson J., Roodman G.D. Antisense inhibition of macrophage inflammatory protein 1-α blocks bone destruction in a model of myeloma bone disease. J Clin Invest. 2001;108(12):1833–1841. https://doi.org/10.1172/JCI13116.Choi S.J., Oba Y., Gazitt Y., Alsina M., Cruz J., Anderson J., Roodman G.D. Antisense inhibition of macrophage inflammatory protein 1-α blocks bone destruction in a model of myeloma bone disease. J Clin Invest. 2001;108(12):1833–1841. https://doi.org/10.1172/JCI13116.Oshima T., Abe M., Asano J., Hara T., Kitazoe K., Sekimoto E. et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood. 2005;106(9):3160–3165. https://doi.org/10.1182/blood-2004-12-4940.Oshima T., Abe M., Asano J., Hara T., Kitazoe K., Sekimoto E. et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood. 2005;106(9):3160–3165. https://doi.org/10.1182/blood-2004-12-4940.Edwards C.M., Edwards J.R., Lwin S.T., Esparza J., Oyajobi B.O., McCluskey B. et al. Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo. Blood. 2008;111(5):2833–2842. https://doi.org/10.1182/blood-2007-03-077685.Edwards C.M., Edwards J.R., Lwin S.T., Esparza J., Oyajobi B.O., McCluskey B. et al. Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo. Blood. 2008;111(5):2833–2842. https://doi.org/10.1182/blood-2007-03-077685.Yaccoby S., Ling W., Zhan F., Walker R., Barlogie B., Shaughnessy J.D.Jr. Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood. 2007;109(5):2106–2111. https://doi.org/10.1182/blood-2006-09-047712.Yaccoby S., Ling W., Zhan F., Walker R., Barlogie B., Shaughnessy J.D.Jr. Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood. 2007;109(5):2106–2111. https://doi.org/10.1182/blood-2006-09-047712.Wang J.H., Zhang Y., Li H.Y., Liu Y.Y., Sun T. Dickkopf-1 negatively regulates the expression of osteoprotegerin, a key osteoclastogenesis inhibitor, by sequestering Lrp6 in primary and metastatic lytic bone lesions. Medicine (Baltimore). 2016;95(24):e3767. https://doi.org/10.1097/MD.0000000000003767.Wang J.H., Zhang Y., Li H.Y., Liu Y.Y., Sun T. Dickkopf-1 negatively regulates the expression of osteoprotegerin, a key osteoclastogenesis inhibitor, by sequestering Lrp6 in primary and metastatic lytic bone lesions. Medicine (Baltimore). 2016;95(24):e3767. https://doi.org/10.1097/MD.0000000000003767.Hiasa M., Okui T., Allette Y.M., Ripsch M.S., Sun-Wada G.H., Wakabayashi H. et al. Bone Pain Induced by Multiple Myeloma Is Reduced by Targeting V-ATPase and ASIC3. Cancer Res. 2017;77(6):1283–1295. https://doi.org/10.1158/0008-5472.CAN-15-3545.Hiasa M., Okui T., Allette Y.M., Ripsch M.S., Sun-Wada G.H., Wakabayashi H. et al. Bone Pain Induced by Multiple Myeloma Is Reduced by Targeting V-ATPase and ASIC3. Cancer Res. 2017;77(6):1283–1295. https://doi.org/10.1158/0008-5472.CAN-15-3545.Nencini S., Ivanusic J. Mechanically sensitive Aδ nociceptors that innervate bone marrow respond to changes in intra-osseous pressure. J Physiol. 2017;595(13):4399–4415. https://doi.org/10.1113/jp273877.Nencini S., Ivanusic J. Mechanically sensitive Aδ nociceptors that innervate bone marrow respond to changes in intra-osseous pressure. J Physiol. 2017;595(13):4399–4415. https://doi.org/10.1113/jp273877.Castañeda-Corral G., Jimenez-Andrade J.M., Bloom A.P., Taylor R.N., Mantyh W.G., Kaczmarska M.J. et al. The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience. 2011;178:196–207. https://doi.org/10.1016/j.neuroscience.2011.01.039.Castañeda-Corral G., Jimenez-Andrade J.M., Bloom A.P., Taylor R.N., Mantyh W.G., Kaczmarska M.J. et al. The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience. 2011;178:196–207. https://doi.org/10.1016/j.neuroscience.2011.01.039.Tando T., Sato Y., Miyamoto K., Morita M., Kobayashi T., Funayama A. et al. Hif1α is required for osteoclast activation and bone loss in male osteoporosis. Biochem Biophys Res Commun. 2016;470(2):391–396. https://doi.org/10.1016/j.bbrc.2016.01.033.Tando T., Sato Y., Miyamoto K., Morita M., Kobayashi T., Funayama A. et al. Hif1α is required for osteoclast activation and bone loss in male osteoporosis. Biochem Biophys Res Commun. 2016;470(2):391–396. https://doi.org/10.1016/j.bbrc.2016.01.033.Terpos E., Zamagni E., Lentzsch S., Drake M.T., García-Sanz R., Abildgaard N. et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol. 2021;22(3):e119–e130. https://doi.org/10.1016/S1470-2045(20)30559-3.Terpos E., Zamagni E., Lentzsch S., Drake M.T., García-Sanz R., Abildgaard N. et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol. 2021;22(3):e119–e130. https://doi.org/10.1016/S1470-2045(20)30559-3.Morgan G.J., Child J.A., Gregory W.M., Szubert A.J., Cocks K., Bell S.E. et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12(8):743–752. https://doi.org/10.1016/S1470-2045(11)70157-7.Morgan G.J., Child J.A., Gregory W.M., Szubert A.J., Cocks K., Bell S.E. et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12(8):743–752. https://doi.org/10.1016/S1470-2045(11)70157-7.Perazella M.A., Markowitz G.S. Bisphosphonate nephrotoxicity. Kidney Int. 2008;74(11):1385–1393. https://doi.org/10.1038/ki.2008.356.Perazella M.A., Markowitz G.S. Bisphosphonate nephrotoxicity. Kidney Int. 2008;74(11):1385–1393. https://doi.org/10.1038/ki.2008.356.Gimsing P., Carlson K., Turesson I., Fayers P., Waage A., Vangsted A. et al. Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial. Lancet Oncol. 2010;11(10):973–982. https://doi.org/10.1016/S1470-2045(10)70198-4.Gimsing P., Carlson K., Turesson I., Fayers P., Waage A., Vangsted A. et al. Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial. Lancet Oncol. 2010;11(10):973–982. https://doi.org/10.1016/S1470-2045(10)70198-4.Coleman R., Hadji P., Body J.J., Santini D., Chow E., Terpos E. et al. Bone health in cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2020;31(12):1650–1663. https://doi.org/10.1016/j.annonc.2020.07.019.Coleman R., Hadji P., Body J.J., Santini D., Chow E., Terpos E. et al. Bone health in cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2020;31(12):1650–1663. https://doi.org/10.1016/j.annonc.2020.07.019.Raje N., Vescio R., Montgomery C.W., Badros A., Munshi N., Orlowski R. et al. Bone Marker-Directed Dosing of Zoledronic Acid for the Prevention of Skeletal Complications in Patients with Multiple Myeloma: Results of the Z-MARK Study. Clin Cancer Res. 2016;22(6):1378–1384. https://doi.org/10.1158/1078-0432.CCR-15-1864.Raje N., Vescio R., Montgomery C.W., Badros A., Munshi N., Orlowski R. et al. Bone Marker-Directed Dosing of Zoledronic Acid for the Prevention of Skeletal Complications in Patients with Multiple Myeloma: Results of the Z-MARK Study. Clin Cancer Res. 2016;22(6):1378–1384. https://doi.org/10.1158/1078-0432.CCR-15-1864.Royle K.L., Gregory W.M., Cairns D.A., Bell S.E., Cook G., Owen R.G. et al. Quality of life during and following sequential treatment of previously untreated patients with multiple myeloma: findings of the Medical Research Council Myeloma IX randomised study. Br J Haematol. 2018;182(6):816–829. https://doi.org/10.1111/bjh.15459.Royle K.L., Gregory W.M., Cairns D.A., Bell S.E., Cook G., Owen R.G. et al. Quality of life during and following sequential treatment of previously untreated patients with multiple myeloma: findings of the Medical Research Council Myeloma IX randomised study. Br J Haematol. 2018;182(6):816–829. https://doi.org/10.1111/bjh.15459.Raje N., Terpos E., Willenbacher W., Shimizu K., García-Sanz R., Durie B. et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018;19(3):370–381. https://doi.org/10.1016/S1470-2045(18)30072-X.Raje N., Terpos E., Willenbacher W., Shimizu K., García-Sanz R., Durie B. et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018;19(3):370–381. https://doi.org/10.1016/S1470-2045(18)30072-X.Kunizawa K., Hiramatsu R., Hoshino J., Mizuno H., Ozawa Y., Sekine A. et al. Denosumab for dialysis patients with osteoporosis: A cohort study. Sci Rep. 2020;10(1):2496. https://doi.org/10.1038/s41598-020-59143-8.Kunizawa K., Hiramatsu R., Hoshino J., Mizuno H., Ozawa Y., Sekine A. et al. Denosumab for dialysis patients with osteoporosis: A cohort study. Sci Rep. 2020;10(1):2496. https://doi.org/10.1038/s41598-020-59143-8.Meredith R.F., Bassler J.R.., McDonald A.M., Stahl J.M., Redden D.T., Bonner J.A. Biological Effective Radiation Dose for Multiple Myeloma Palliation. Adv Radiat Oncol. 2023;8(4):101214. https://doi.org/10.1016/j.adro.2023.101214.Meredith R.F., Bassler J.R.., McDonald A.M., Stahl J.M., Redden D.T., Bonner J.A. Biological Effective Radiation Dose for Multiple Myeloma Palliation. Adv Radiat Oncol. 2023;8(4):101214. https://doi.org/10.1016/j.adro.2023.101214.Rades D., Conde-Moreno A.J., Cacicedo J., Segedin B., Rudat V., Schild S.E. Excellent outcomes after radiotherapy alone for malignant spinal cord compression from myeloma. Radiol Oncol. 2016;50(3):337–340. Available at: https://pubmed.ncbi.nlm.nih.gov/27679551.Rades D., Conde-Moreno A.J., Cacicedo J., Segedin B., Rudat V., Schild S.E. Excellent outcomes after radiotherapy alone for malignant spinal cord compression from myeloma. Radiol Oncol. 2016;50(3):337–340. Available at: https://pubmed.ncbi.nlm.nih.gov/27679551.Rudzianskiene M., Inciura A., Gerbutavicius R., Rudzianskas V., Macas A., Simoliuniene R. et al. Single vs. multiple fraction regimens for palliative radiotherapy treatment of multiple myeloma: A prospective randomized study. Strahlenther Onkol. 2017;193(9):742–749. https://doi.org/10.1007/s00066-017-1154-5.Rudzianskiene M., Inciura A., Gerbutavicius R., Rudzianskas V., Macas A., Simoliuniene R. et al. Single vs. multiple fraction regimens for palliative radiotherapy treatment of multiple myeloma: A prospective randomized study. Strahlenther Onkol. 2017;193(9):742–749. https://doi.org/10.1007/s00066-017-1154-5.Fabregat C., Almendros S., Navarro-Martin A., Gonzalez J. Pain Flare-Effect Prophylaxis With Corticosteroids on Bone Radiotherapy Treatment: A Systematic Review. Pain Pract. 2020;20(1):101–109. https://doi.org/10.1111/papr.12823.Fabregat C., Almendros S., Navarro-Martin A., Gonzalez J. Pain Flare-Effect Prophylaxis With Corticosteroids on Bone Radiotherapy Treatment: A Systematic Review. Pain Pract. 2020;20(1):101–109. https://doi.org/10.1111/papr.12823.Валиев А.К., Соколовский А.В., Неред А.С., Мусаев Э.Р. Малоинвазивные хирургические технологии при поражениях позвоночника в онкогематологии. Клиническая онкогематология. 2013;(2):177–194. Режим доступа: https://bloodjournal.ru/wp-content/uploads/2015/11/6-Stranitsy-izOnco_2_2013_-6.pdfValiyev A.K., Sokolovskiy A.V., Nered A.S., Musayev E.R. Minimally invasive surgical techniques in hematological malignancies with spinal involvement. Clinical Oncohematology. 2013;(2):177–194. (In Russ.) Available at: https://bloodjournal.ru/wp-content/uploads/2015/11/6-Stranitsy-izOnco_2_2013_-6.pdfEseonu K.C., Panchmatia J.R., Streetly M.J., Grauer J.N., Fakouri B. The role of Vertebral Augmentation Procedures in the management of vertebral compression fractures secondary to multiple myeloma. Hematol Oncol. 2022;10.1002/hon.3102. https://doi.org/10.1002/hon.3102.Eseonu K.C., Panchmatia J.R., Streetly M.J., Grauer J.N., Fakouri B. The role of Vertebral Augmentation Procedures in the management of vertebral compression fractures secondary to multiple myeloma. Hematol Oncol. 2022;10.1002/hon.3102. https://doi.org/10.1002/hon.3102.Fallon M., Giusti R., Aielli F., Hoskin P., Rolke R., Sharma M., Ripamonti C.I. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(Suppl. 4):iv166–iv191. https://doi.org/10.1093/annonc/mdy152.Fallon M., Giusti R., Aielli F., Hoskin P., Rolke R., Sharma M., Ripamonti C.I. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(Suppl. 4):iv166–iv191. https://doi.org/10.1093/annonc/mdy152.Семочкин С.В. Новые ингибиторы протеасомы в терапии множественной миеломы. Онкогематология. 2019;14(2):29–40. https://doi.org/10.17650/1818-8346-2019-14-2-29-40.Semochkin S.V. New proteasome inhibitors in the management of multiple myeloma. Oncogematologiya. 2019;14(2):29–40. (In Russ.) https://doi.org/10.17650/1818-8346-2019-14-2-29-40.Ohashi Y., Yatabe M., Niijima D., Imamura A., Nagayama Y., Otsuka K. et al. Importance of Compliance With Guidelines for the Prevention of VaricellaZoster Virus Reactivation in Multiple Myeloma. In Vivo. 2021;35(6):3289–3296. https://doi.org/10.21873/invivo.12624.Ohashi Y., Yatabe M., Niijima D., Imamura A., Nagayama Y., Otsuka K. et al. Importance of Compliance With Guidelines for the Prevention of VaricellaZoster Virus Reactivation in Multiple Myeloma. In Vivo. 2021;35(6):3289–3296. https://doi.org/10.21873/invivo.12624.Henze L., Buhl C., Sandherr M., Cornely O.A., Heinz W.J., Khodamoradi Y. et al. Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus. Ann Hematol. 2022;101(3):491–511. https://doi.org/10.1007/s00277-021-04746-y.Henze L., Buhl C., Sandherr M., Cornely O.A., Heinz W.J., Khodamoradi Y. et al. Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus. Ann Hematol. 2022;101(3):491–511. https://doi.org/10.1007/s00277-021-04746-y.Strasfeld L., Chou S. Antiviral drug resistance: mechanisms and clinical implications. Infect Dis Clin North Am. 2010;24(3):809–833. https://doi.org/10.1016/j.idc.2010.07.001.Strasfeld L., Chou S. Antiviral drug resistance: mechanisms and clinical implications. Infect Dis Clin North Am. 2010;24(3):809–833. https://doi.org/10.1016/j.idc.2010.07.001.Finnerup N.B., Attal N., Haroutounian S., McNicol E., Baron R., Dworkin R.H. et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–173. https://doi.org/10.1016/S1474-4422(14)70251-0.Finnerup N.B., Attal N., Haroutounian S., McNicol E., Baron R., Dworkin R.H. et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–173. https://doi.org/10.1016/S1474-4422(14)70251-0.Derry S., Rice A.S., Cole P., Tan T., Moore R.A. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;1(1):CD007393. https://doi.org/10.1002/14651858.CD007393.pub4.Derry S., Rice A.S., Cole P., Tan T., Moore R.A. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;1(1):CD007393. https://doi.org/10.1002/14651858.CD007393.pub4.Stubblefield M.D., Burstein H.J., Burton A.W., Custodio C.M., Deng G.E., Ho M. et al. NCCN task force report: management of neuropathy in cancer. J Natl Compr Canc Netw. 2009;7(5):1–26. https://doi.org/10.6004/jnccn.2009.0078.Stubblefield M.D., Burstein H.J., Burton A.W., Custodio C.M., Deng G.E., Ho M. et al. NCCN task force report: management of neuropathy in cancer. J Natl Compr Canc Netw. 2009;7(5):1–26. https://doi.org/10.6004/jnccn.2009.0078.Selvy M., Kerckhove N., Pereira B., Barreau F., Nguyen D., Busserolles J. et al. Prevalence of Chemotherapy-Induced Peripheral Neuropathy in Multiple Myeloma Patients and its Impact on Quality of Life: A Single Center CrossSectional Study. Front Pharmacol. 2021;12:637593. https://doi.org/10.3389/fphar.2021.637593.Selvy M., Kerckhove N., Pereira B., Barreau F., Nguyen D., Busserolles J. et al. Prevalence of Chemotherapy-Induced Peripheral Neuropathy in Multiple Myeloma Patients and its Impact on Quality of Life: A Single Center CrossSectional Study. Front Pharmacol. 2021;12:637593. https://doi.org/10.3389/fphar.2021.637593.Richardson P.G., Sonneveld P., Schuster M.W., Stadtmauer E.A., Facon T., Harousseau J.L. et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol. 2009;144(6):895–903. https://doi.org/10.1111/j.1365-2141.2008.07573.x.Richardson P.G., Sonneveld P., Schuster M.W., Stadtmauer E.A., Facon T., Harousseau J.L. et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol. 2009;144(6):895–903. https://doi.org/10.1111/j.1365-2141.2008.07573.x.Arnulf B., Pylypenko H., Grosicki S., Karamanesht I., Leleu X., van de Velde H. et al. Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica. 2012;97(12):1925–1928. https://doi.org/10.3324/haematol.2012.067793.Arnulf B., Pylypenko H., Grosicki S., Karamanesht I., Leleu X., van de Velde H. et al. Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica. 2012;97(12):1925–1928. https://doi.org/10.3324/haematol.2012.067793.Dimopoulos M.A., Moreau P., Palumbo A., Joshua D., Pour L., Hájek R. et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27–38. https://doi.org/10.1016/S1470-2045(15)00464-7.Dimopoulos M.A., Moreau P., Palumbo A., Joshua D., Pour L., Hájek R. et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27–38. https://doi.org/10.1016/S1470-2045(15)00464-7.Yan W., Wu Z., Zhang Y., Hong D., Dong X., Liu L. et al. The molecular and cellular insight into the toxicology of bortezomib-induced peripheral neuropathy. Biomed Pharmacother. 2021;142:112068. https://doi.org/10.1016/j.biopha.2021.112068.Yan W., Wu Z., Zhang Y., Hong D., Dong X., Liu L. et al. The molecular and cellular insight into the toxicology of bortezomib-induced peripheral neuropathy. Biomed Pharmacother. 2021;142:112068. https://doi.org/10.1016/j.biopha.2021.112068.Li Y., Lustberg M.B., Hu S. Emerging Pharmacological and Non-Pharmacological Therapeutics for Prevention and Treatment of ChemotherapyInduced Peripheral Neuropathy. Cancers (Basel). 2021;13(4):766. https://doi.org/10.3390/cancers13040766.Li Y., Lustberg M.B., Hu S. Emerging Pharmacological and Non-Pharmacological Therapeutics for Prevention and Treatment of ChemotherapyInduced Peripheral Neuropathy. Cancers (Basel). 2021;13(4):766. https://doi.org/10.3390/cancers13040766.Geyer H.L., Gazelka H., Mesa R. How I treat pain in hematologic malignancies safely with opioid therapy. Blood. 2020;135(26):2354–2364. https://doi.org/10.1182/blood.2019003116.Geyer H.L., Gazelka H., Mesa R. How I treat pain in hematologic malignancies safely with opioid therapy. Blood. 2020;135(26):2354–2364. https://doi.org/10.1182/blood.2019003116.Chou R., Turner J.A., Devine E.B., Hansen R.N., Sullivan S.D., Blazina I. et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(4):276–286. https://doi.org/10.7326/m14-2559.Chou R., Turner J.A., Devine E.B., Hansen R.N., Sullivan S.D., Blazina I. et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(4):276–286. https://doi.org/10.7326/m14-2559.Lee M., Silverman S.M., Hansen H., Patel V.B., Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145–161. Available at: https://pubmed.ncbi.nlm.nih.gov/21412369.Lee M., Silverman S.M., Hansen H., Patel V.B., Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145–161. Available at: https://pubmed.ncbi.nlm.nih.gov/21412369.Klimas J., Gorfinkel L., Fairbairn N., Amato L., Ahamad K., Nolan S. et al. Strategies to Identify Patient Risks of Prescription Opioid Addiction When Initiating Opioids for Pain: A Systematic Review. JAMA Netw Open. 2019;2(5):e193365. https://doi.org/10.1001/jamanetworkopen.2019.3365.Klimas J., Gorfinkel L., Fairbairn N., Amato L., Ahamad K., Nolan S. et al. Strategies to Identify Patient Risks of Prescription Opioid Addiction When Initiating Opioids for Pain: A Systematic Review. JAMA Netw Open. 2019;2(5):e193365. https://doi.org/10.1001/jamanetworkopen.2019.3365.Corder G., Castro D.C., Bruchas M.R., Scherrer G. Endogenous and Exogenous Opioids in Pain. Annu Rev Neurosci. 2018;41:453–473. https://doi.org/10.1146/annurev-neuro-080317-061522.Corder G., Castro D.C., Bruchas M.R., Scherrer G. Endogenous and Exogenous Opioids in Pain. Annu Rev Neurosci. 2018;41:453–473. https://doi.org/10.1146/annurev-neuro-080317-061522.Schol J., Wauters L., Dickman R., Drug V., Mulak A., Serra J. et al. United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United European Gastroenterol J. 2021;9(3):287–306. https://doi.org/10.1002/ueg2.12060.Schol J., Wauters L., Dickman R., Drug V., Mulak A., Serra J. et al. United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United European Gastroenterol J. 2021;9(3):287–306. https://doi.org/10.1002/ueg2.12060.Meissner W., Leyendecker P., Mueller-Lissner S., Nadstawek J., Hopp M., Ruckes C. et al. A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain. 2009;13(1):56–64. https://doi.org/10.1016/j.ejpain.2008.06.012.Meissner W., Leyendecker P., Mueller-Lissner S., Nadstawek J., Hopp M., Ruckes C. et al. A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain. 2009;13(1):56–64. https://doi.org/10.1016/j.ejpain.2008.06.012.Coluzzi F., Scerpa M.S., Centanni M. The Effect of Opiates on Bone Formation and Bone Healing. Curr Osteoporos Rep. 2020;18(3):325–335. https://doi.org/10.1007/s11914-020-00585-4.Coluzzi F., Scerpa M.S., Centanni M. The Effect of Opiates on Bone Formation and Bone Healing. Curr Osteoporos Rep. 2020;18(3):325–335. https://doi.org/10.1007/s11914-020-00585-4.Coluzzi F., Rolke R., Mercadante S. Pain Management in Patients with Multiple Myeloma: An Update. Cancers (Basel). 2019;11(12):2037. https://doi.org/10.3390/cancers11122037.Coluzzi F., Rolke R., Mercadante S. Pain Management in Patients with Multiple Myeloma: An Update. Cancers (Basel). 2019;11(12):2037. https://doi.org/10.3390/cancers11122037.Nguyen J., Luk K., Vang D., Soto W., Vincent L., Robiner S. et al. Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer. Br J Anaesth. 2014;113(Suppl. 1):i4–i13. https://doi.org/10.1093/bja/aeu090.Nguyen J., Luk K., Vang D., Soto W., Vincent L., Robiner S. et al. Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer. Br J Anaesth. 2014;113(Suppl. 1):i4–i13. https://doi.org/10.1093/bja/aeu090.Haque M.R., Barlass U., Armstrong A., Shaikh M., Bishehsari F. Novel role of the Mu-opioid receptor in pancreatic cancer: potential link between opioid use and cancer progression. Mol Cell Biochem. 2022;477(5):1339–1345.https://doi.org/10.1007/s11010-022-04377-5.Haque M.R., Barlass U., Armstrong A., Shaikh M., Bishehsari F. Novel role of the Mu-opioid receptor in pancreatic cancer: potential link between opioid use and cancer progression. Mol Cell Biochem. 2022;477(5):1339–1345.https://doi.org/10.1007/s11010-022-04377-5.Cata J.P., Keerty V., Keerty D., Feng L., Norman P.H., Gottumukkala V. et al. A retrospective analysis of the effect of intraoperative opioid dose on cancer recurrence after non-small cell lung cancer resection. Cancer Med. 2014;3(4):900–908. https://doi.org/10.1002/cam4.236.Cata J.P., Keerty V., Keerty D., Feng L., Norman P.H., Gottumukkala V. et al. A retrospective analysis of the effect of intraoperative opioid dose on cancer recurrence after non-small cell lung cancer resection. Cancer Med. 2014;3(4):900–908. https://doi.org/10.1002/cam4.236.Exadaktylos A.K., Buggy D.J., Moriarty D.C., Mascha E., Sessler D.I. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006;105(4):660–604. https://doi.org/10.1097/00000542-200610000-00008.Exadaktylos A.K., Buggy D.J., Moriarty D.C., Mascha E., Sessler D.I. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006;105(4):660–604. https://doi.org/10.1097/00000542-200610000-00008.Cao L.H., Li H.T., Lin W.Q., Tan H.Y., Xie L., Zhong Z.J., Zhou J.H. Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts. Sci Rep. 2016;6:18706. https://doi.org/10.1038/srep18706.Cao L.H., Li H.T., Lin W.Q., Tan H.Y., Xie L., Zhong Z.J., Zhou J.H. Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts. Sci Rep. 2016;6:18706. https://doi.org/10.1038/srep18706.Bhoir S., Uhelski M., Guerra-Londono J.J., Cata J.P. The Role of Opioid Receptors in Cancer. Adv Biol (Weinh). 2023;e2300102. https://doi.org/10.1002/adbi.202300102.Bhoir S., Uhelski M., Guerra-Londono J.J., Cata J.P. The Role of Opioid Receptors in Cancer. Adv Biol (Weinh). 2023;e2300102. https://doi.org/10.1002/adbi.202300102.Фирсова М.В., Менделеева Л.П., Соловьев М.В., Рехтина И.Г., Покровская О.С., Урнова Е.С. и др. Трансплантация аутологичных стволовых клеток крови больным множественной миеломой, осложненной диализ-зависимой почечной недостаточностью. Терапевтический архив. 2020;92(7):70–76. https://doi.org/10.26442/00403660.2020.07.000777.Firsova M.V., Mendeleeva L.P., Solovev M.V., Rekhtina I.G., Pokrovskaya O.S., Urnova E.S. et al. Autologous haematopoietic stem cell transplantation in patients with multiple myeloma complicated by dialysis-dependent renal failure. Terapevticheskii Arkhiv. 2020;92(7):70–76. (In Russ.) https://doi.org/10.26442/00403660.2020.07.000777.Sweiss K., Hofmeister C.C., Quigley J.G., Sweis J.G., Kurzweil K., Sborov D.W. et al. Chronic Opioid Use Is Highly Prevalent and Associated with Inferior Survival in Myeloma Patients in Remission after Autologous Transplant. Blood. 2022;140(Suppl. 1):5252–5253. https://doi.org/10.1182/blood-2022-171045.Sweiss K., Hofmeister C.C., Quigley J.G., Sweis J.G., Kurzweil K., Sborov D.W. et al. Chronic Opioid Use Is Highly Prevalent and Associated with Inferior Survival in Myeloma Patients in Remission after Autologous Transplant. Blood. 2022;140(Suppl. 1):5252–5253. https://doi.org/10.1182/blood-2022-171045.Danish M.L., Shah M.R., Lin Y., Ho J.K., Copeland T.M., Cooper D.L. Persistent opioid use in patients with multiple myeloma post-ASCT. Eur J Haematol. 2022;108(6):503–509. https://doi.org/10.1111/ejh.13759.Danish M.L., Shah M.R., Lin Y., Ho J.K., Copeland T.M., Cooper D.L. Persistent opioid use in patients with multiple myeloma post-ASCT. Eur J Haematol. 2022;108(6):503–509. https://doi.org/10.1111/ejh.13759.Семочкин С.В., Желнова Е.И., Мисюрина Е.Н., Марьин Д.С., Ушакова А.И., Каримова Е.А. и др. Клиническое значение восстановления функции почек у больных с впервые диагностированной множественной миеломой, осложненной тяжелой и диализ-зависимой почечной недостаточностью. Гематология и трансфузиология. 2019;64(3):283–296. https://doi.org/10.35754/0234-5730-2019-64-3-283-296.Semochkin S.V., Zhelnova E.I., Misyurina E.N., Maryin D.S., Ushakova A.I., Karimova E.A. et al. Clinical importance of renal recover on outcomes of newly diagnosed multiple myeloma patients with severe and dialysis-dependent kidney failure. Gematologiya i Transfuziologiya. 2019;64(3):283– 296. (In Russ.) https://doi.org/10.35754/0234-5730-2019-64-3-283-296.Coluzzi F. Assessing and Treating Chronic Pain in Patients with End-Stage Renal Disease. Drugs. 2018;78(14):1459–1479. https://doi.org/10.1007/s40265-018-0980-9.Coluzzi F. Assessing and Treating Chronic Pain in Patients with End-Stage Renal Disease. Drugs. 2018;78(14):1459–1479. https://doi.org/10.1007/s40265-018-0980-9.Coluzzi F., Raffa R.B., Pergolizzi J., Rocco A., Locarini P., Cenfra N. et al. Tapentadol prolonged release for patients with multiple myeloma suffering from moderate-to-severe cancer pain due to bone disease. J Pain Res. 2015;8:229–238. https://doi.org/10.2147/JPR.S83490.Coluzzi F., Raffa R.B., Pergolizzi J., Rocco A., Locarini P., Cenfra N. et al. Tapentadol prolonged release for patients with multiple myeloma suffering from moderate-to-severe cancer pain due to bone disease. J Pain Res. 2015;8:229–238. https://doi.org/10.2147/JPR.S83490.Moreau P., Karamanesht I.I., Domnikova N., Kyselyova M.Y., Vilchevska K.V., Doronin V.A. et al. Pharmacokinetic, pharmacodynamic and covariate analysis of subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma. Clin Pharmacokinet. 2012;51(12):823–829. https://doi.org/10.1007/s40262-012-0010-0.Moreau P., Karamanesht I.I., Domnikova N., Kyselyova M.Y., Vilchevska K.V., Doronin V.A. et al. Pharmacokinetic, pharmacodynamic and covariate analysis of subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma. Clin Pharmacokinet. 2012;51(12):823–829. https://doi.org/10.1007/s40262-012-0010-0.Gupta N., Hanley M.J., Xia C., Labotka R., Harvey R.D., Venkatakrishnan K. Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor. Clin Pharmacokinet. 2019;58(4):431–449. https://doi.org/10.1007/s40262-018-0702-1.Gupta N., Hanley M.J., Xia C., Labotka R., Harvey R.D., Venkatakrishnan K. Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor. Clin Pharmacokinet. 2019;58(4):431–449. https://doi.org/10.1007/s40262-018-0702-1.Kasserra C., Assaf M., Hoffmann M., Li Y., Liu L., Wang X. et al. Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015;55(2):168–178. https://doi.org/10.1002/jcph.384.Kasserra C., Assaf M., Hoffmann M., Li Y., Liu L., Wang X. et al. Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015;55(2):168–178. https://doi.org/10.1002/jcph.384.Tennant F. Opioid regimens in patients with chronic pain with multiple cytochrome P450 defects. J Opioid Manag. 2015;11(3):237–242. https://doi.org/10.5055/jom.2015.0272.Tennant F. Opioid regimens in patients with chronic pain with multiple cytochrome P450 defects. J Opioid Manag. 2015;11(3):237–242. https://doi.org/10.5055/jom.2015.0272.Абузарова Г.Р., Косоруков В.С., Гамзелева О.Ю., Сарманаева Р.Р., Бражникова Ю.В. Эффективность и безопасность препарата Тафалгин у пациентов с онкологической болью. Результаты открытого сравнительного многоцентрового рандомизированного клинического исследования. Онкология. Журнал им. П.А. Герцена. 2022;11(5):38–48. https://doi.org/10.17116/onkolog20221105138.Abuzarova G.R., Kosorukov V.S., Gamzeleva O.Yu., Sarmanaeva R.R., Brazhnicova Yu.V. The efficacy and safety of Tafalgin in patients with cancer pain. Results of an open-label comparative multicenter randomized clinical trial. P.A. Herzen Journal of Oncology. 2022;11(5):38–48. (In Russ.) https://doi.org/10.17116/onkolog20221105138.

The authors declare that there are no conflicts of interest present.