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Volume 24, Issue 14
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873

Abstract

Objective

The purpose of this study was to identify predictive and risk factors for the development of immune-related endocrinopathies and to analyze the incidence and characteristics of immune-related endocrinopathies in our population.

Design

A retrospective, single-centre cohort carried out at Gregorio Marañón Hospital between January 2018 -December 2019.

Methods

A total of 163 patients were enrolled. In January 2018 and December 2019, we treated patients who underwent ICI treatment in the Medical Oncology Department of General University Hospital Gregorio Marañón, a tertiary care public hospital in Madrid, as part of an observational, retrospective, single-center cohort study.

Results

Endocrinopathies were diagnosed in 19.5% of the patients (n = 32). The tumours with the highest incidence of endocrinopathies were non-small cell lung cancer (25,9%), kidney cell cancer (25%) and hepatocarcinoma (20%). Among the 32 patients who developed endocrinopathy, 18,8%, 19,13%, and 21,28% received anti-CTLA-4, anti-PD-1 and anti-PDL-1, respectively. Thyroid dysfunction was the most frequent endocrinopathy (12,8%). A higher percentage of patients with negative antiTPO and antiTG antibodies developed G1 hypothyroidism compared to patients with positive antibodies who developed a higher proportion of G2 hypothyroidism. The presence of an initial phase of thyrotoxicity was not related to greater severity. We observed longer progression-free survival in patients who developed thyroid dysfunction.

Conclusion

Pre-existing antibodies were independently associated with endocrinopathies. Moreover, our study let us conclude that the presence of thyroid autoantibodies may be related to its severity. It is important to determine anti-thyroid antibodies prior to the start of immunotherapy as a risk factor for thyroid dysfunction, which in turn is a prognostic marker.

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2024-02-14
2025-01-09

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References

  1. ChangL.S. Barroso-SousaR. TolaneyS.M. HodiF.S. KaiserU.B. MinL. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints.Endocr. Rev.2019401176510.1210/er.2018‑0000630184160
     [Google Scholar]
  2. Barroso-SousaR. BarryW.T. Garrido-CastroA.C. HodiF.S. MinL. KropI.E. TolaneyS.M. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens.JAMA Oncol.20184217318210.1001/jamaoncol.2017.306428973656
     [Google Scholar]
  3. de FiletteJ. AndreescuC. CoolsF. BravenboerB. VelkeniersB. A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors.Horm. Metab. Res.201951314515610.1055/a‑0843‑336630861560
     [Google Scholar]
  4. ShangY. ZhangY. LiJ. LiP. ZhangX. Risk of endocrine adverse events in cancer patients treated with PD-1 inhibitors: A systematic review and meta-analysis.Immunotherapy20179326127210.2217/imt‑2016‑014728231723
     [Google Scholar]
  5. CorselloS.M. BarnabeiA. MarchettiP. De VecchisL. SalvatoriR. TorinoF. Endocrine side effects induced by immune checkpoint inhibitors.J. Clin. Endocrinol. Metab.20139841361137510.1210/jc.2012‑407523471977
     [Google Scholar]
  6. Abdel-RahmanO. ElHalawaniH. FouadM. Risk of endocrine complications in cancer patients treated with immune check point inhibitors: A meta-analysis.Future Oncol.201612341342510.2217/fon.15.22226775673
     [Google Scholar]
  7. FerrariS.M. FallahiP. GalettaF. CitiE. BenvengaS. AntonelliA. Thyroid disorders induced by checkpoint inhibitors.Rev. Endocr. Metab. Disord.201819432533310.1007/s11154‑018‑9463‑230242549
     [Google Scholar]
  8. Freites-MartinezA. SantanaN. Arias-SantiagoS. VieraA. Using the common terminology criteria for adverse events (CTCAE - version 5.0) to evaluate the severity of adverse events of anticancer therapies.Actas Dermosifiliogr.20211121909210.1016/j.ad.2019.05.00932891586
     [Google Scholar]
  9. González-RodríguezE. Rodríguez-AbreuD. Immune checkpoint inhibitors: Review and management of endocrine adverse events.Oncologist201621780481610.1634/theoncologist.2015‑050927306911
     [Google Scholar]
  10. BrahmerJ.R. LacchettiC. SchneiderB.J. AtkinsM.B. BrassilK.J. CaterinoJ.M. ChauI. ErnstoffM.S. GardnerJ.M. GinexP. HallmeyerS. Holter ChakrabartyJ. LeighlN.B. MammenJ.S. McDermottD.F. NaingA. NastoupilL.J. PhillipsT. PorterL.D. PuzanovI. ReichnerC.A. SantomassoB.D. SeigelC. SpiraA. Suarez-AlmazorM.E. WangY. WeberJ.S. WolchokJ.D. ThompsonJ.A. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline.J. Clin. Oncol.201836171714176810.1200/JCO.2017.77.638529442540
     [Google Scholar]
  11. HighamC.E. Olsson-BrownA. CarrollP. CooksleyT. LarkinJ. LoriganP. MorgansteinD. TrainerP.J. Society for endocrinology endocrine emergency guidance: Acute management of the endocrine complications of checkpoint inhibitor therapy.Endocr. Connect.201877G1G710.1530/EC‑18‑006829930025
     [Google Scholar]
  12. SuQ. ZhangX. WangD. ZhangH. ZhuC. HouY. LiuJ. GaoZ. The risk of immune-related endocrine disorders associated with anti-PD-1 inhibitors therapy for solid tumors: A systematic review and meta-analysis.Int. Immunopharmacol.20185932833810.1016/j.intimp.2018.04.02129679857
     [Google Scholar]
  13. LuJ. YangJ. LiangY. MengH. ZhaoJ. ZhangX. Incidence of immune checkpoint inhibitor-associated diabetes: A meta-analysis of randomized controlled studies.Front. Pharmacol.201910145310.3389/fphar.2019.0145331920646
     [Google Scholar]
  14. MaherV.E. FernandesL.L. WeinstockC. TangS. AgarwalS. BraveM. NingY. SinghH. SuzmanD. XuJ. GoldbergK.B. SridharaR. IbrahimA. TheoretM. BeaverJ.A. PazdurR. Analysis of the association between adverse events and outcome in patients receiving a programmed death protein 1 or programmed death ligand 1 antibody.J. Clin. Oncol.201937302730273710.1200/JCO.19.0031831116675
     [Google Scholar]
  15. AttiaP. PhanG.Q. MakerA.V. RobinsonM.R. QuezadoM.M. YangJ.C. SherryR.M. TopalianS.L. KammulaU.S. RoyalR.E. RestifoN.P. HaworthL.R. LevyC. MavroukakisS.A. NicholG. YellinM.J. RosenbergS.A. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4.J. Clin. Oncol.200523256043605310.1200/JCO.2005.06.20516087944
     [Google Scholar]
  16. Freeman-KellerM. KimY. CroninH. RichardsA. GibneyG. WeberJ.S. Nivolumab in resected and unresectable metastatic melanoma: Characteristics of immune-related adverse events and association with outcomes.Clin. Cancer Res.201622488689410.1158/1078‑0432.CCR‑15‑113626446948
     [Google Scholar]
  17. HarataniK. HayashiH. ChibaY. KudoK. YonesakaK. KatoR. KanedaH. HasegawaY. TanakaK. TakedaM. NakagawaK. Association of immune-related adverse events with nivolumab efficacy in non–small-cell lung cancer.JAMA Oncol.20184337437810.1001/jamaoncol.2017.292528975219
     [Google Scholar]
  18. RicciutiB. GenovaC. De GiglioA. BassanelliM. Dal BelloM.G. MetroG. BrambillaM. BaglivoS. GrossiF. ChiariR. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: Long-term outcomes from a multi-institutional analysis.J. Cancer Res. Clin. Oncol.2019145247948510.1007/s00432‑018‑2805‑330506406
     [Google Scholar]
  19. EggermontA.M.M. KicinskiM. BlankC.U. MandalaM. LongG.V. AtkinsonV. DalleS. HaydonA. KhattakA. CarlinoM.S. SandhuS. LarkinJ. PuigS. AsciertoP.A. RutkowskiP. SchadendorfD. KoornstraR. Hernandez-AyaL. Di GiacomoA.M. van den EertweghA.J.M. GrobJ.J. GutzmerR. JamalR. LoriganP.C. KreplerC. IbrahimN. MarreaudS. van AkkooiA. RobertC. SuciuS. Association between immune-related adverse events and recurrence-free survival among patients with stage III melanoma randomized to receive pembrolizumab or placebo.JAMA Oncol.20206451952710.1001/jamaoncol.2019.557031895407
     [Google Scholar]
  20. OkenM.M. CreechR.H. TormeyD.C. HortonJ. DavisT.E. McFaddenE.T. CarboneP.P. Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am. J. Clin. Oncol.19825664965610.1097/00000421‑198212000‑000147165009
     [Google Scholar]
  21. AnicK. VarcholaJ. SchmidtM.W. SchwabR. LinzV.C. SchmidtM. HardtR. HartmannE.K. RuckesC. HasenburgA. BattistaM.J. Influence of interdisciplinary frailty screening on perioperative complication rates in elderly ovarian cancer patients: Results of a retrospective observational study.Arch. Gynecol. Obstet.202230761929194010.1007/s00404‑022‑06850‑436434440
     [Google Scholar]
  22. PostowM.A. CallahanM.K. WolchokJ.D. Immune checkpoint blockade in cancer therapy.J. Clin. Oncol.201533171974198210.1200/JCO.2014.59.435825605845
     [Google Scholar]
  23. BuchbinderE.I. DesaiA. CTLA-4 and PD-1 pathways.Am. J. Clin. Oncol.20163919810610.1097/COC.000000000000023926558876
     [Google Scholar]
  24. CardonaZ. SosmanJ.A. ChandraS. HuangW. Endocrine side effects of immune checkpoint inhibitors.Front. Endocrinol. (Lausanne)202314115780510.3389/fendo.2023.115780537251665
     [Google Scholar]
  25. KennedyR. AwadaH. VuraN. CilteaD. MoroccoM. Endocrinopathies from checkpoint inhibitors: Incidence, outcomes, and management.Cleve. Clin. J. Med.202390530731710.3949/ccjm.90a.2203237127339
     [Google Scholar]
  26. KurimotoC. InabaH. AriyasuH. IwakuraH. UedaY. UrakiS. TakeshimaK. FurukawaY. MoritaS. YamamotoY. YamashitaS. KatsudaM. HayataA. AkamatsuH. JinninM. HaraI. YamaueH. AkamizuT. Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune‐checkpoint inhibitors.Cancer Sci.202011151468147710.1111/cas.1436332086984
     [Google Scholar]
  27. ShalitA. SarantisP. KoustasE. TrifylliE.M. MatthaiosD. KaramouzisM.V. Predictive biomarkers for immune-related endocrinopathies following immune checkpoint inhibitors treatment.Cancers (Basel)202315237510.3390/cancers1502037536672324
     [Google Scholar]
  28. MuirC.A. Clifton-BlighR.J. LongG.V. ScolyerR.A. LoS.N. CarlinoM.S. TsangV.H.M. MenziesA.M. Thyroid immune-related adverse events following immune checkpoint inhibitor treatment.J. Clin. Endocrinol. Metab.20211069e3704e371310.1210/clinem/dgab26333878162
     [Google Scholar]
  29. ToiY. SugawaraS. SugisakaJ. OnoH. KawashimaY. AibaT. KawanaS. SaitoR. AsoM. TsurumiK. SuzukiK. ShimizuH. DomekiY. TerayamaK. NakamuraA. YamandaS. KimuraY. HondaY. Profiling preexisting antibodies in patients treated with anti–PD-1 therapy for advanced non–small cell lung cancer.JAMA Oncol.20195337638310.1001/jamaoncol.2018.586030589930
     [Google Scholar]
  30. BasakE.A. van der MeerJ.W.M. HurkmansD.P. SchreursM.W.J. Oomen-de HoopE. van der VeldtA.A.M. BinsS. JoosseA. KoolenS.L.W. DebetsR. PeetersR.P. AertsJ.G.J.V. MathijssenR.H.J. MediciM. Overt thyroid dysfunction and anti-thyroid antibodies predict response to anti-PD-1 immunotherapy in cancer patients.Thyroid202030796697310.1089/thy.2019.072632151195
     [Google Scholar]
  31. AndoT. UedaA. OgawaK. MotooI. KajiuraS. NakajimaT. HiranoK. OkumuraT. TsukadaK. HaraT. SuzukiN. NakadaN. HorikawaN. FujiiT. YasudaI. Prognosis of immune-related adverse events in patients with advanced gastric cancer treated with nivolumab or pembrolizumab: A multicenter retrospective analysis.In Vivo202135147548210.21873/invivo.1228133402499
     [Google Scholar]
  32. MuirC.A. WoodC.C.G. Clifton-BlighR.J. LongG.V. ScolyerR.A. CarlinoM.S. MenziesA.M. TsangV.H.M. Association of antithyroid antibodies in checkpoint inhibitor–associated thyroid immune–related adverse events.J. Clin. Endocrinol. Metab.20221075e1843e184910.1210/clinem/dgac05935104870
     [Google Scholar]
  33. PercikR. CrisenoS. AdamS. YoungK. MorgansteinD.L. Diagnostic criteria and proposed management of immune-related endocrinopathies following immune checkpoint inhibitor therapy for cancer.Endocr. Connect.2023125e22051310.1530/EC‑22‑051336884258
     [Google Scholar]
  34. IwamaS. KobayashiT. YasudaY. ArimaH. Immune checkpoint inhibitor-related thyroid dysfunction.Best Pract. Res. Clin. Endocrinol. Metab.202236310166010.1016/j.beem.2022.10166035501263
     [Google Scholar]
  35. ZouF. Abu-SbeihH. MaW. PengY. QiaoW. WangJ. ShahA.Y. Glitza OlivaI.C. Piha-PaulS.A. ThompsonJ.A. ZhangH.C. ThomasA.S. WangY. Association of chronic immune-mediated diarrhea and colitis with favorable cancer response.J. Natl. Compr. Canc. Netw.202119670070810.6004/jnccn.2020.764733316767
     [Google Scholar]
  36. SuoA. ChanY. BeaulieuC. KongS. CheungW.Y. MonzonJ.G. SmylieM. WalkerJ. MorrisD. ChengT. Anti-PD1-induced immune-related adverse events and survival outcomes in advanced melanoma.Oncologist202025543844610.1634/theoncologist.2019‑067432048768
     [Google Scholar]
  37. BottlaenderL. Amini-AdleM. Maucort-BoulchD. RobinsonP. ThomasL. DalleS. Cutaneous adverse events: A predictor of tumour response under anti‐ PD ‐1 therapy for metastatic melanoma, a cohort analysis of 189 patients.J. Eur. Acad. Dermatol. Venereol.20203492096210510.1111/jdv.1631132078191
     [Google Scholar]
  38. SchweizerC. SchubertP. RutznerS. EcksteinM. HaderleinM. LettmaierS. SemrauS. GostianA.O. FreyB. GaiplU.S. ZhouJ.G. FietkauR. HechtM. Prospective evaluation of the prognostic value of immune-related adverse events in patients with non-melanoma solid tumour treated with PD-1/PD-L1 inhibitors alone and in combination with radiotherapy.Eur. J. Cancer2020140556210.1016/j.ejca.2020.09.00133045663
     [Google Scholar]
  39. AkamatsuH. MurakamiE. OyanagiJ. ShibakiR. KakiT. TakaseE. TanakaM. HarutaniY. YamagataN. OkudaY. FurutaK. SugimotoT. TeraokaS. HayataA. TokudomeN. OzawaY. MoriK. KohY. YamamotoN. Immune-related adverse events by immune checkpoint inhibitors significantly predict durable efficacy even in responders with advanced non-small cell lung cancer.Oncologist2020254e679e68310.1634/theoncologist.2019‑029932297443
     [Google Scholar]
  40. IndiniA. Di GuardoL. CimminielloC. PrisciandaroM. RandonG. De BraudF. Del VecchioM. Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma.J. Cancer Res. Clin. Oncol.2019145251152110.1007/s00432‑018‑2819‑x30539281
     [Google Scholar]
  41. ShankarB. ZhangJ. NaqashA.R. FordeP.M. FelicianoJ.L. MarroneK.A. EttingerD.S. HannC.L. BrahmerJ.R. RicciutiB. OwenD. ToiY. WalkerP. OttersonG.A. PatelS.H. SugawaraS. NaidooJ. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non–small cell lung cancer.JAMA Oncol.20206121952195610.1001/jamaoncol.2020.501233119034
     [Google Scholar]
  42. YamauchiI. YasodaA. MatsumotoS. SakamoriY. KimY.H. NomuraM. OtsukaA. YamasakiT. SaitoR. KitamuraM. KitawakiT. HishizawaM. Kawaguchi-SakitaN. FujiiT. TauraD. SoneM. InagakiN. Incidence, features, and prognosis of immune-related adverse events involving the thyroid gland induced by nivolumab.PLoS One2019145e021695410.1371/journal.pone.021695431086392
     [Google Scholar]
  43. KobayashiT. IwamaS. YasudaY. OkadaN. OkujiT. ItoM. OnoueT. GotoM. SugiyamaM. TsunekawaT. TakagiH. HagiwaraD. ItoY. SugaH. BannoR. YokotaK. HaseT. MoriseM. HashimotoN. AndoM. FujimotoY. HibiH. SoneM. AndoY. AkiyamaM. HasegawaY. ArimaH. Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: A prospective study.J. Immunother. Cancer202082e00077910.1136/jitc‑2020‑00077932606047
     [Google Scholar]
  44. FajeA.T. LawrenceD. FlahertyK. FreedmanC. FaddenR. RubinK. CohenJ. SullivanR.J. High‐dose glucocorticoids for the treatment of ipilimumab‐induced hypophysitis is associated with reduced survival in patients with melanoma.Cancer2018124183706371410.1002/cncr.3162929975414
     [Google Scholar]
  45. Del RiveroJ. CordesL.M. Klubo-GwiezdzinskaJ. MadanR.A. NiemanL.K. GulleyJ.L. Endocrine-related adverse events related to immune checkpoint inhibitors: Proposed algorithms for management.Oncologist202025429030010.1634/theoncologist.2018‑047032297436
     [Google Scholar]
  46. SpagnoloC.C. GiuffridaG. CannavòS. FranchinaT. SilvestrisN. RuggeriR.M. SantarpiaM. Management of endocrine and metabolic toxicities of immune-checkpoint inhibitors: from clinical studies to a real-life scenario.Cancers (Basel)202215124610.3390/cancers1501024636612243
     [Google Scholar]
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Endocrine Adverse Events Related To Immune Checkpoint Inhibitor Treatment: Relationship Between Antibodies and Severity of Thyroid Dysfunction
Endocr Metab Immune Disord Drug Targets 24, 1628 (2024); https://doi.org/10.2174/0118715303280679240206100137
/content/journals/emiddt/10.2174/0118715303280679240206100137
/content/journals/emiddt/10.2174/0118715303280679240206100137
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  • Article Type:     Research Article
Keyword(s): endocrinopathies; ICI; PFS; severity; thyroid antibodies; thyroid dysfunction

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