Gives Some Pause About Checkpoint Inhibitors: Possible Link to Type 1 Diabetes

One percent of patients undergoing immunotherapy for cancer develop type 1 diabetes, what Mario Sznol, MD, an oncologist at Yale School of Medicine, described in Stat as an “unfortunate trade-off.” Sznol is treating Rich Lenihan with checkpoint inhibitors for Lenihan’s skin cancer. Jamie Vidal, who is not one of Sznol’s patients but whose diabetes also resulted from the immunotherapy, put it another way in the same Stat article: “Type 1 diabetes is like being in hell, man. It’s horrible.”

After his third dose of immunotherapy, Lenihan was weak, tired, urinating constantly, and always thirsty. A blood test revealed his type 1 diabetes. He’ll need to control his glucose with insulin injections for the rest of his life. Control can be tricky, too, because some patients develop “brittle” diabetes, in which insulin levels swing crazily from very high to very low, or vice versa.

Three not-for-profit organizations have launched a three-year, $10 million research initiative that will try to get to the root of checkpoint inhibitor-induced diabetes in cancer patients—and perhaps find out even more, said Ben Williams, MD, of the Helmsley Charitable Trust, one of the organizations spearheading the effort. “We believe that this research may reveal profound discoveries relevant to all forms of type 1 diabetes, potentially leading to new biomarkers for detection and treatment,” he said in a statement. The other two organizations involved are the Parker Institute for Cancer Immunotherapy and JDRF (formerly the Juvenile Diabetes Research Foundation).

About 1.25 million Americans have type 1 diabetes. It’s usually diagnosed during childhood and adolescence. But, at least anecdotally, age does not seem to factor into who gets checkpoint inhibitor-induced diabetes: Lenihan is 62; Vidal, 79.

Jeffrey Bluestone, the CEO of the Parker Institute, said in a press release that “nobody truly understands how or why” some patients taking checkpoint inhibitors such as ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda) develop insulin-dependent diabetes. “This is of increasing importance as more patients are being treated with checkpoint inhibitors and other immunotherapies.”

The grant money will fund a prospective study that will track 1,500 to 2,000 patients undergoing checkpoint inhibitor therapy at clinics and hospitals across the nation. Researchers will collect blood samples periodically, subjecting the samples to genomics and other technologies that they hope will suss out causative biomarkers in those patients who develop diabetes.