Renal injury during combination immunotherapy (ipilimumab + nivolumab) in patients with metastatic renal cell cancer who previously underwent nephrectomy

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Aim. To estimate frequency and type of renal injury in patients with metastatic renal cell carcinoma (RCC) receiving ipilimumab and nivolumab after nephrectomy.

Materials and methods. The retrospective study involved 50 patients, including 38 (76%) men and 12 (24%) women with a single kidney and progressive metastatic RCC. After nephrectomy before the start of immunotherapy for the progression of RCC, chronic kidney disease (CKD) stage 3 and higher was diagnosed in 39 (78%) cases.

Results. During immunotherapy, acute kidney injury (AKI) developed in 9 (11%) patients after 14 weeks of treatment. The maximum incidence of AKI (n=7; 25%) was documented after the 10th administration of the drugs. When assessing the dynamics of creatinine levels over 28 weeks, a significant increase was noted after the 2nd, 3rd, 4th and 10th administrations. After the 2nd administration of the drugs, the creatinine level in the total sample of patients increased on average to 159.7 μmol/l with a baseline level of 127.8 μmol/l (p<0.001), while after the 3rd, 4th and 10th administration to 160.3, 151.6 and 147.9 μmol/l, respectively (p<0.039, p=0.003 and p=0.029, respectively). Similar dynamics were also seen for urea with a significant increase after the 2nd, 3rd, 4th, 5th and 7th administrations. For example, the maximum urea level was recorded after the 3rd and 5th administrations of the drugs and was 10.2 mmol/l, while before the start of therapy it was 8.1 mmol/l (p=0.001 and p=0.003, respectively).

Conclusion. A significant renal injury was seen during 28 weeks of follow-up in patients with metastatic RCC after nephrectomy receiving ipilimumab and nivolumab.

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作者简介

Konstantin Titov

S.P. Botkin’s State Clinical Hospital; Peoples' Friendship University of Russia

Email: alimov.oncologist@gmail.com
ORCID iD: 0000-0003-4460-9136
SPIN 代码: 7795-6512
Scopus 作者 ID: 921470

Ph.D., MD, professor, leading researcher, Professor at the Department of the Oncology and Interventional Radiology named after V.P. Kharchenko 

俄罗斯联邦, 125284, Moscow, 2nd Botkinsky proezd, 5; 17198, Moscow, Miklukho-Maklaya st., 6

Maya Epifanova

Peoples' Friendship University of Russia

Email: alimov.oncologist@gmail.com
ORCID iD: 0000-0002-8398-7255

Ph.D., MD, professor at the Department of Urology and Operative Nephrology with a course of Oncourology

俄罗斯联邦, 117198, Moscow, Miklukho-Maklaya st., 6

Artemy Alimov

S.P. Botkin’s State Clinical Hospital; Peoples' Friendship University of Russia

编辑信件的主要联系方式.
Email: alimov.oncologist@gmail.com
ORCID iD: 0009-0003-4479-683X
SPIN 代码: 7957-6484
Scopus 作者 ID: 1186684

Oncologist at the Outpatient Oncology Care Center, Ph.D. student at the Department of the Oncology and Interventional Radiology named after V.P. Kharchenko 

俄罗斯联邦, 125284, Moscow, 2nd Botkinsky proezd, 5; 17198, Moscow, Miklukho-Maklaya st., 6

Olga Nesterova

Lomonosov Moscow State University

Email: alimov.oncologist@gmail.com
ORCID iD: 0000-0003-3355-4547
SPIN 代码: 9662-7522
Scopus 作者 ID: 1111567

Ph.D., researcher at the Department of Urology and Andrology of Medical Scientific and Educational Center, senior tutor of the Department of Urology and Andrology of Faculty of Fundamental Medicine

俄罗斯联邦, 119192, Moscow, Lomonosovsky Prospekt, 27, bldg

Evgeniy Shutov

S.P. Botkin’s State Clinical Hospital; FGBOU DPO RMANPO

Email: alimov.oncologist@gmail.com
ORCID iD: 0000-0002-1047-0378

Ph.D., MD, professor, Chief of Interdistrict Nephrology Center, Head of the Department of Nephrology and Hemodialysis 

俄罗斯联邦, 125284, Moscow, 2nd Botkinsky proezd, 5; 125993, Moscow, Barrikadnaya st., 2/1, building 1

Sergey Lebedev

S.P. Botkin’s State Clinical Hospital; FGBOU DPO RMANPO

Email: alimov.oncologist@gmail.com
ORCID iD: 0000-0001-5366-1281

Ph.D., MD, Associate Professor, Leading Researcher, Deputy Chief Physician for Oncology, Professor at the Department of Surgery, Faculty of Surgery 

俄罗斯联邦, 125284, Moscow, 2nd Botkinsky proezd, 5; 125993, Moscow, Barrikadnaya st., 2/1, building 1

Gadzhimurad Zapirov

Peoples' Friendship University of Russia

Email: alimov.oncologist@gmail.com
ORCID iD: 0000-0003-2347-4615

Ph.D., associate professor at the Department of the Oncology and Interventional Radiology named after V.P. Kharchenko 

俄罗斯联邦, 117198, Moscow, Miklukho-Maklaya st., 6

参考

  1. Cancer Today. https://gco.iarc.fr/today/home.
  2. Heng D.Y.C., Wells J.C., Rini B.I. et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. European urology. 2014;66(4):704-710. doi: 10.1016/j.eururo.2014.05.034
  3. Ko J.J., Xie W., Kroeger N. et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. The Lancet Oncology. 2015;16(3):293-300. doi: 10.1016/S1470-2045(14)71222-7
  4. Attalla K., Weng S., Voss M.H., Hakimi A.A. Epidemiology, Risk Assessment, and Biomarkers for Patients with Advanced Renal Cell Carcinoma. The Urologic clinics of North America. 2020;47(3):293-303. doi: 10.1016/j.ucl.2020.04.002
  5. Powles T., Albiges L., Bex A. et al. Renal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of oncology : official journal of the European Society for Medical Oncology. 2024;35(8):692-706. doi: 10.1016/j.annonc.2024.05.537
  6. Liu C., Wei W., Yang L. et al. Incidence and risk factors of acute kidney injury in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Frontiers in immunology. 2023;14:1173952. doi: 10.3389/fimmu.2023.1173952
  7. Choueiri T.K., Motzer R.J. Systemic Therapy for Metastatic Renal-Cell Carcinoma. The New England journal of medicine. 2017;376(4):354-366. doi: 10.1056/NEJMra1601333
  8. Narang A., Gebrael G., Jo Y. et al. Effectiveness of Second-Line Cabozantinib in Metastatic Clear Cell Renal Cell Carcinoma Patients After First-Line Treatment with Immune Checkpoint Inhibitor-based Combinations. Kidney cancer (Clifton, Va). 2024;8(1):135-142. doi: 10.3233/KCA-240016
  9. Barragan-Carrillo R., Saad E., Saliby R.M. et al. First and Second-line Treatments in Metastatic Renal Cell Carcinoma. European urology. Published online November 2024. doi: 10.1016/j.eururo.2024.10.019
  10. FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-plus-ipilimumab-combination-intermediate-or-poor-risk-adv.
  11. Motzer R.J., Tannir N.M., McDermott D.F. et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. The New England journal of medicine. 2018;378(14):1277-1290. doi: 10.1056/NEJMoa1712126
  12. Manohar S., Kompotiatis P., Thongprayoon C., Cheungpasitporn W., Herrmann J., Herrmann S.M. Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;34(1):108-117. doi: 10.1093/ndt/gfy105
  13. Rosellini M., Tassinari E., Marchetti A. et al. An update on safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma. Expert opinion on drug safety. 2023;22(4):279-291. doi: 10.1080/14740338.2023.2203486
  14. Levin A., Ahmed S.B., Carrero J.J.. et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney international. 2024;105(4):684-701. doi: 10.1016/j.kint.2023.10.016
  15. Starzer A.M., Wolff L., Popov P., Kiesewetter B., Preusser M., Berghoff A.S. The more the merrier? Evidence and efficacy of immune checkpoint- and tyrosine kinase inhibitor combinations in advanced solid cancers. Cancer treatment reviews. 2024;125:102718. doi: 10.1016/j.ctrv.2024.102718
  16. Motzer R.J., Russo P., Grünwald V. et al. Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomised, phase 3 trial. Lancet (London, England). 2023;401(10379):821-832. doi: 10.1016/S0140-6736(22)02574-0
  17. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical practice. 2012;120(4):c179-84. doi: 10.1159/000339789
  18. Levey A.S., Stevens L.A., Schmid C.H. et al. A new equation to estimate glomerular filtration rate. Annals of internal medicine. 2009;150(9):604-612. doi: 10.7326/0003-4819-150-9-200905050-00006
  19. Perazella M.A., Sprangers B. AKI in Patients Receiving Immune Checkpoint Inhibitors. Clinical journal of the American Society of Nephrology : CJASN. 2019;14(7):1077-1079. doi: 10.2215/CJN.02340219
  20. El Rassy E., Bakouny Z., Yared F., Chelala D.N., El Karak F., Ghosn M. The nephrotoxicity of immune checkpoint inhibitor-based combinations. European journal of cancer (Oxford, England : 1990). 2018;103:274-278. doi: 10.1016/j.ejca.2018.07.126
  21. Puzanov I., Diab A., Abdallah K. et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. Journal for immunotherapy of cancer. 2017;5(1):95. doi: 10.1186/s40425-017-0300-z
  22. Wanchoo R., Karam S., Uppal N.N. et al. Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review. American journal of nephrology. 2017;45(2):160-169. doi: 10.1159/000455014
  23. Liu F., Wang Z., Li X. et al. Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors. Cancer communications (London, England). 2023;43(2):214-224. doi: 10.1002/cac2.12396
  24. Valentin A., Møller A.K.H., Palshof J.A. et al. Combination therapy with immune check point inhibitors and acute kidney injury. Acta oncologica (Stockholm, Sweden). 2023;62(2):121-125. doi: 10.1080/0284186X.2023.2176255
  25. Xie W., Xiao S., Li X., Huang J., Li G., Zhang Z. Incidence, mortality, and risk factors of acute kidney injury after immune checkpoint inhibitors: Systematic review and meta-analysis of real-world evidence. European journal of internal medicine. 2023;115:88-95. doi: 10.1016/j.ejim.2023.05.034
  26. Koks M.S., Ocak G., Suelmann B.B.M. et al. Immune checkpoint inhibitor-associated acute kidney injury and mortality: An observational study. PloS one. 2021;16(6):e0252978. doi: 10.1371/journal.pone.0252978
  27. Gromova E.G., Biryukova L.S., Dzhumabayeva B.T., Kurmukov I.A. Practical recommendations for the correction of nephrotoxicity of antitumor drugs. Practical recommendations of RUSSCO, part 2. Malignant tumors. 2023;13(3S2):153-166. Russian (Громова Е.Г., Бирюкова Л.С., Джумабаева Б.Т., Курмуков И.А. Практические рекомендации по коррекции нефротоксичности противоопухолевых препаратов. Практические рекомендации RUSSCO, часть 2. Злокачественные опухоли. 2023;13(3S2):153-166).
  28. Volkova M.I., Alekseev B.Y.A., Gladkov O.A., Matveev W.B., Nosov D. Practical recommendations for the drug treatment of renal cell carcinoma. Practical recommendations of RUSSCO. Malignant tumors. 2022;12(3s2):579-588. Russian (Волкова МИ, Алексеев БЯ, Гладков ОА, Матвеев ВБ, Носов Д. Практические рекомендации по лекарственному лечению почечноклеточного рака. Практические рекомендации RUSSCO. Злокачественные опухоли. 2022;12(3s2):579-588).

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2. Ris. 1. Chastota razvitiya povrezhdeniya yedinstvennoy pochki v techeniye 28 nedel' kombinirovannoy immunoterapii (ipilimumab + nivolumab) u patsiyentov s metastaticheskim PKR, raneye perenesshikh nefrektomiyu 194 / 5 000 Fig. 1. Incidence of solitary kidney injury during 28 weeks of combination immunotherapy (ipilimumab + nivolumab) in patients with metastatic RCC who previously underwent nephrectomy

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3. Fig. 2. Incidence of AKI during 28 weeks of combination immunotherapy (ipilimumab + nivolumab) in patients with metastatic RCC with a solitary kidney

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