|Year : 2016 | Volume
| 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 Publication||24-Feb-2017|
National Oncology Center, The Royal Hospital, Muscat
Sultanate of Oman
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Venniyoor A. Immune checkpoint inhibitors for Indian patients: A note of caution. Indian J Cancer 2016;53:468-9
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. 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.
Patients from developing countries suffer more severe manifestations of multisystem autoimmune diseases., 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. Data also suggest that non-Caucasians (including Indians) suffer more graft versus host disease (GVHD) after allogeneic stem cell transplant, another autoimmune phenomenon.
Predisposition to autoimmunity could be related to higher exposure to “crowd infections” 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. Indeed, it has been proposed that GVHD could be also due to microflora mismatch between donor and recipient. “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”). Remarkably, even in wealthy countries, diseases such as lupus are more severe in neighborhoods with low socioeconomic status.
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).
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 ,,, are from whites, and a smaller percentage from Japanese  and South Koreans. 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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