Contents

Search

drug adverse effects of checkpoint inhibitor(s)

Adverse effects: - may increase risk of autoimmune disease [1] - inflammatory arthritis & sicca syndrome induced by nivolumab & ipilimumab [1] - rheumatoid arthritis & polymyalgia rheumatica associated with ipilimumab (Yervoy), nivolumab (Opdivo), pembrolizumab (Keytruda) [3] - wide range of immune-related adverse effects [4] - all checkpoint inhibitors associated with diabetes mellitus type 1 & adrenal insufficiency [16] - immune checkpoint inhibitor therapy is not associated with increased mortality in cancer patients with COVID-19 [12] - autoimmune hepatitis [14] - lymphocytic hypophysitis [14] - hyperprogression of cancer [13] - neurological complications (3%) [2] - myopathy, neuropathy - cerebellar ataxia - internuclear ophthalmoplegia - retinopathy - headache - colitis, hypophysitis, rash more common with CTLA-4 inhibitors - pneumonitis, hypothyroidism, arthralgia, vitiligo more common with PD-1 inhibitors [5] - myocarditis [6,7] - thyroid dysfunction, hypothyroidism 13.4%, hyperthyroidism 9.5% [11] - cutaneous manifestations (30-60%) [17] - maculopapular rash, pruritus, vitiligo (most common) - xanthems, lichenoid reactions, psoriasis, bullous disorders [17] - Stevens-Johnson syndrome or toxic epidermal necrolysis [17] - sclerodermoid reaction, morphea* - multiple studies suggest a favorable association of subtypes of cutaneous manifestations with clinical response & survival [17] - small increase in incidence of pulmonary embolism in patients with metastatic lung cancer 17% vs 14.6% [18] * guidelines for management of toxicity [9] - discontinuation of drug + high-dose IV glucocorticoid [8] * toclizumab for glucocorticoid-resistant morphea [15] Monitor: - echocardiogram to monitor myocarditis [10]

Properties

GENERAL: drug adverse effect(s) of DRUGS: checkpoint inhibitor FORM: drug adverse effects checkpoint inhibitor

References

  1. Cappelli LC et al. Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis 2017 Jan; 76:43 PMID: 28000525 Free Article
  2. George J Neurological Events Rare with Anti-PD-1 Therapy More cases expected as immunotherapy for metastatic cancer expands. MedPage Today. September 05, 2017 https://www.medpagetoday.com/Neurology/GeneralNeurology/67694
  3. Belkhir R, Burel SL, Dunogeant L et al. Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment. Ann Rheum Dis 2017 Oct; 76:1747 PMID: 28600350 http://ard.bmj.com/content/76/10/1747
  4. Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med 2018; 378:158-168. January 11, 2018 PMID: 29320654 http://www.nejm.org/doi/full/10.1056/NEJMra1703481
  5. Khoja L, Day D, Wei-Wu Chen T, Siu LL, Hansen AR. Tumour- and Class-specific Patterns of Immune-Related Adverse Events of Immune Checkpoint Inhibitors. Ann Oncol. 2017;28(10):2377-2385. PMID: 28945858 https://www.medscape.com/viewarticle/890539
  6. Johnson DB, Balko JM, Compton ML et al Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016 Nov 3;375(18):1749-1755. PMID: 27806233 Free PMC Article
  7. Mahmood SS et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 2018 Apr 24; 71:1755. PMID: 29567210 https://www.sciencedirect.com/science/article/pii/S0735109718333680 - Tocchetti CG et al. Cardiac toxicity in patients treated with immune checkpoint inhibitors: It is now time for cardio-immuno-oncology. J Am Coll Cardiol 2018 Apr 24; 71:1765 PMID: 29567211 https://www.sciencedirect.com/science/article/pii/S0735109718333692
  8. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
  9. Fuerst ML New Guidelines Outline Management of Immunotherapy Side Effects. Emerging patterns suggest checkpoint inhibitors may cause problems in several organ systems. MedPage Today. ASCO Reading Room. Feb 8, 2018 https://www.medpagetoday.com/reading-room/asco/immunotherapy/71026 - Haanen J, Carbonnel F, Kerr RK et al Management of Toxicities from Immunotherapy: ESMO Clinical Practice Guidelines Ann Oncol (2017) 28 (suppl 4): iv119-iv142 http://www.esmo.org/Guidelines/Supportive-and-Palliative-Care/Management-of-Toxicities-from-Immunotherapy
  10. Lou N. Cardiac Echo Tracks Checkpoint Inhibitor Damage - Global longitudinal strain can flag cardiac injury before EF falls. MedPage Today. Feb 03, 2020 https://www.medpagetoday.com/cardiology/chf/84682 - Awadalla M, Mahmood SS, Groarke JD et al Global longitudinal strain and cardiac events in patients with immune checkpoint inhibitor-related myocarditis. J Am Coll Cardiol Feb 2020; 75(5). PMID: 32029128 http://www.onlinejacc.org/content/75/5/467 - Abraham TP, Aras MA Echo-strain to check up on checkpoint inhibitors. J Am Coll Cardiol Feb 2020; 75(5) PMID: 32029129 http://www.onlinejacc.org/content/75/5/479
  11. Monaco K How Prevalent Is Checkpoint Inhibitor Thyroid Dysfunction, Really? - Real-world data offer word of caution for oncologists. MedPage Today. April 1, 2020 https://www.medpagetoday.com/meetingcoverage/endo/85750 - Quandt Z et al Finding the Needles in the Haystack: Harnessing the Electronic Health Record to Find Thyroid Immune Related Adverse Events. ENDO 2020; Abstract SAT-418
  12. Worcester S Immune Checkpoint Inhibitors Don't Increase Death Risk for COVID-19 Cancer Patients. Medscape - Aug 07, 2020. https://www.medscape.com/viewarticle/935370
  13. Park HJ, Kim KW, Won SE et al Definition, Incidence, and Challenges for Assessment of Hyperprogressive Disease During Cancer Treatment With Immune Checkpoint Inhibitors. A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4(3):e211136. March 24 PMID: 33760090 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777859 - Sehgal K Hyperprogression in Patients With Cancer Receiving Immune Checkpoint Inhibitors. JAMA Netw Open. 2021;4(3):e211839. PMID: 33760084 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777853
  14. Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 10, American College of Physicians, Philadelphia 2015, 2018, 2022.
  15. Blaise M, Cardot-Leccia N, Seitz-Polski B et al Tocilizumab for Corticosteroid-Refractory Immune Checkpoint Inhibitor- Induced Generalized Morphea. JAMA Dermatol. Published online November 30, 2022. PMID: 36449277 https://jamanetwork.com/journals/jamadermatology/fullarticle/2798842
  16. NEJM Knowledge+ Complex Medical Care - Barroso-Sousa R, Barry WT, Garrido-Castro AC et al Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2018 Feb 1;4(2):173-182. PMID: 28973656 PMCID: PMC5838579 Free PMC article.
  17. Du Y, Wu W, Chen M et al Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment. A Systematic Review and Meta-Analysis. JAMA Dermatol. Published online September 6, 2023. PMID: 37672255 https://jamanetwork.com/journals/jamadermatology/fullarticle/2808778
  18. Kahn K Checkpoint Inhibitors for Lung Cancer Linked to Pulmonary Embolism. Study raises questions about how to assess patient risk, experts say. MedPage Today. October 8, 2024 https://www.medpagetoday.com/meetingcoverage/chest/112306