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  Table of Contents  
Year : 2016  |  Volume : 53  |  Issue : 3  |  Page : 468-469

Immune checkpoint inhibitors for Indian patients: A note of caution

National Oncology Center, The Royal Hospital, Muscat, Sultanate of Oman

Date of Web Publication24-Feb-2017

Correspondence Address:
A Venniyoor
National Oncology Center, The Royal Hospital, Muscat
Sultanate of Oman
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.200660

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How to cite this article:
Venniyoor A. Immune checkpoint inhibitors for Indian patients: A note of caution. Indian J Cancer 2016;53:468-9

How to cite this URL:
Venniyoor A. Immune checkpoint inhibitors for Indian patients: A note of caution. Indian J Cancer [serial online] 2016 [cited 2020 Jun 4];53:468-9. Available from:

Immune checkpoint inhibitors such as nivolumab and pembrolizumab have dramatically altered the natural history of hard-to-treat cancers such as melanoma, renal cell cancers, and lung cancers, with some long-term survival data.[1] They work by activating the body's immune system (predominantly T cells) against antigens expressed on tumor cells. Their major side effect is, expectedly, autoimmune disease, causing colitis, hepatitis, dermatitis, and endocrine deficiencies.[2]

Patients from developing countries suffer more severe manifestations of multisystem autoimmune diseases.[3],[4] This could be due late diagnosis in the native countries lacking access to health care, but is also seen in the wealthier countries they migrate to.[5] Data also suggest that non-Caucasians (including Indians) suffer more graft versus host disease (GVHD) after allogeneic stem cell transplant, another autoimmune phenomenon.[6]

Predisposition to autoimmunity could be related to higher exposure to “crowd infections”[7] during childhood in countries with lower hygiene. Laboratory animals brought up in germ-free atmosphere – gnotobiotic-suffer less autoimmune diseases, even if genetically bred to be susceptible.[8] Indeed, it has been proposed that GVHD could be also due to microflora mismatch between donor and recipient.[9] “Crowd infections” result in higher antigenic load and we may have to pay a price when exposed to drugs that are basically broad-spectrum immune-stimulants (“Crowd infections” should be differentiated from infections by “old friends” – gut microbiota and helminths with whom we have evolved, and are protective against allergy and autoimmune diseases, as proposed in the “hygiene hypothesis”).[7] Remarkably, even in wealthy countries, diseases such as lupus are more severe in neighborhoods with low socioeconomic status.[10]

Unfortunately, unlike in the case of targeted agents, these side effects may not translate into increased efficacy, though more data on this are awaited (2015 ASCO Educational Book).[2]

The effect of ethnicity on incidence and severity of side effects have not been studied (personal communication from Bristol-Myers Squibb (BMS) and Merck Sharpe & Dohme (MSD)). As can be seen [Table 1], most of the data [11],[12],[13],[14] are from whites, and a smaller percentage from Japanese [13] and South Koreans.[14] Phase IV studies including postmarketing surveillance studies are de rigueur when multinational companies market their products. It is hoped that drug companies make a special effort to record and report the autoimmune side effects of their drugs in India (and other third world countries). And that medical oncologists planning to use these drugs equip themselves with the expertise to diagnose and treat these side effects early and effectively.
Table 1: Ethnicity of patients administered immune checkpoint inhibitors drugs in selected trials

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kourie HR, Awada G, Awada AH. Learning from the tsunami of immune checkpoint inhibitors in 2015. Crit Rev Oncol Hematol 2016;101:213-20.  Back to cited text no. 1
Postow MA. Managing immune checkpoint-blocking antibody side effects. Am Soc Clin Oncol Educ Book 2015:76-83.  Back to cited text no. 2
Tikly M, Navarra SV. Lupus in the developing world – Is it any different? Best Pract Res Clin Rheumatol 2008;22:643-55.  Back to cited text no. 3
Mody GM, Cardiel MH. Challenges in the management of rheumatoid arthritis in developing countries. Best Pract Res Clin Rheumatol 2008;22:621-41.  Back to cited text no. 4
Rees F, Doherty M, Grainge M, Davenport G, Lanyon P, Zhang W. The incidence and prevalence of systemic lupus erythematosus in the UK, 1999-2012. Ann Rheum Dis 2016;75:136-41.  Back to cited text no. 5
Karanth M, Begum G, Cook M, Lawson S, Porter C, Lister N, et al. Increased acute GvHD and higher transplant-related mortality in non-caucasians undergoing standard sibling allogeneic stem cell transplantation. Bone Marrow Transplant 2006;37:419-23.  Back to cited text no. 6
Rook GA, Raison CL, Lowry CA. Microbial 'old friends', immunoregulation and socioeconomic status. Clin Exp Immunol 2014;177:1-12.  Back to cited text no. 7
Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernández-Sueiro JL, et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 1994;180:2359-64.  Back to cited text no. 8
Singh HP, Gupta S, Raju GM, Kochupillai V. Redefining 'self': The role of microflora (commensals) mismatch in the development of GvHD after allogeneic stem cell transplantation and some possible remedies. Med Hypotheses 2001;56:448-50.  Back to cited text no. 9
Trupin L, Tonner MC, Yazdany J, Julian LJ, Criswell LA, Katz PP, et al. The role of neighborhood and individual socioeconomic status in outcomes of systemic lupus erythematosus. J Rheumatol 2008;35:1782-8.  Back to cited text no. 10
Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015;373:123-35.  Back to cited text no. 11
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373:1627-39.  Back to cited text no. 12
Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1803-13.  Back to cited text no. 13
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2016;387:1540-50.  Back to cited text no. 14


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