Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis
BMJ 2018; 360 doi: https://doi.org/10.1136/bmj.k793 (Published 14 March 2018) Cite this as: BMJ 2018;360:k793
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The meta-analysis of Baxi et al. is instructive(1). It helps clinicians to better counsel patients regarding the risks of immune checkpoint blockade and instances in which medical attention should be sought.
The authors’ search methods are robust but do not interrogate an important source namely, VigiBase(http://www.vigiaccess.org/: 2,3). This is the World Health Organisation's system for reporting suspected side effects of various medications. Hence the systematic review overlooks fulminant myocarditis associated with immune checkpoint blockade. This important condition has attracted increasing attention in the medical literature due to its very aggressive natural history and exceedingly high mortality rate, reported at 42%(3,4). Irrespective of its rarity, clinicians are duty bound to inform patients of the risk following the new standard of consent espoused in Montgomery v Lanarkshire Healthboard. In addition, patients must be informed to seek medical attention expeditiously should suggestive symptoms of pericarditis arise within the context of immune checkpoint blockage use. Clinicians should be equally vigilant of patients presenting under this pretext.
1.Baxi S, Yang A, Gennarelli RL, Khan N, Wang Z, Boyce L, Korenstein D. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ. 2018 Mar 14;360:k793. doi: 10.1136/bmj.k793
2. Lindquist, M. VigiBase, the WHO global ICSR database system: basic facts. Drug Inf J. 2008; 42: 409–419
3. Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018 Mar 10;391(10124):933
4. Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA Jr, Anders RA, Sosman JA, Moslehi JJ Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016 Nov 3;375(18):1749-1755
5. Chan SW, Tulloch E, Cooper ES, Smith A, Wojcik W, Norman JE. Montgomery and informed consent: where are we now? BMJ. 2017 May 12;357:j2224
Competing interests: No competing interests
Combination immune checkpoint blockade carries a higher risk of adverse events
Baxi et al perform a clinically useful systematic review of the risk of adverse events attendant to immune check point blockade(1). However the authors did not make a distinction between the use of the immune checkpoint blockade indiviudally or in combination. This is significant; as the body of evidence elsewhere suggests the risk of a number of sequelae to be considerably higher when anti-tumour immune checkpoint blockade agents are used in combination(2,3). It is thus not clear of the risks identified in the review relate to these agents used singularly are combined. Extra vigilance is required in this context both for patients and doctors.
1.Baxi S, Yang A, Gennarelli RL, Khan N, Wang Z, Boyce L, Korenstein D. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ. 2018 Mar 14;360:k793. doi: 10.1136/bmj.k793
2.Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018 Mar 10;391(10124):933
3.Cheng F, Loscalzo J. Autoimmune Cardiotoxicity of Cancer Immunotherapy. Trends Immunol. 2017 Feb;38(2):77-78
Competing interests: No competing interests