There wasn’t much more they could do for Emily. Usually they support low blood pressure with two medications; Emily was on three. She was on the most powerful ventilator they had to support her breathing. They had her on 100 percent oxygen and then added in nitric oxide, which also can support breathing. Many of those IV lines going into her were antibiotics, even though they didn’t think her problems were due to infection. Emily was also receiving three blood products: plasma, platelets to control bleeding, and red blood cells because her bone marrow was still not producing them.
As a bone marrow transplant doctor, Dr. Grupp had seen many patients who were very sick, and he knew that most patients who are that sick don’t make it. The fact that Emily made it through the night created a sense of urgency for Dr. Grupp and the rest of the scientists working on keeping her alive. As Dr. Grupp later said, “We’d gotten through one night when Emily was not supposed to survive. It’s like when somebody climbs Mount Everest. Nobody survives two nights on Everest. We were not going to get her through the next night.”
One of the reactions the doctors predicted Emily might have was called cytokine release syndrome, CRS, when large numbers of white blood cells are activated or overproduced, causing inflammation and the production of cytokines, throwing the patient’s system out of whack. They call this inflammatory response a cytokine storm, and Emily had some of the symptoms of that: high fever, rapid heart rate, difficulty breathing, and low blood pressure.
In the emails back and forth that night, the doctors didn’t know what they should do next. They had given Emily a drug called Enbrel to block some of the inflammation in her immune system, and the steroids, but still she continued to get worse. Her temperature dropped for a little while, but it popped right back up to 104.9.
Part of the scientific infrastructure that Dr. June had built at Penn Medicine was an amazing system of labs to perform detailed analysis and investigation into individuals’ tumors, immune systems, and body chemistries so that they could better understand how the CAR–T cell therapy was working. In addition to Dr. Levine, who had developed a groundbreaking method of growing T cells, he had recruited Dr. Michael Kalos, who developed ways to analyze how the infused T cells were expanding in patients, where they were going, how they were functioning, and if they were destroying the tumor cells.
As part of this research, Dr. Kalos had developed a series of biochemical and molecular assays to perform on blood samples they’d collected from patients before the CAR–T cell infusion and every few days after the infusion, so the doctors could monitor any changes. Typically, Dr. Kalos’s plan was to run the assessments once a month on all the samples collected so the lab could get a holistic view of what was happening in a patient to identify patterns and trends. Dr. Kalos later told me that doctors generally don’t use tests designed for scientific research to make clinical decisions on treating a patient.
But because Emily was so sick and the time was so short and the clinical team could not figure out what was going wrong with Emily using standard clinical tests, Dr. Kalos agreed to run a biochemical test on a week’s worth of blood samples, hoping that the tests might reveal something that could help save her life. Usually the full test takes two days to complete, but Dr. Kalos discussed with his lab staff how sick Emily was, and how much scientific research into CAR–T cell therapy depended on trying to save her. The staff agreed to start the tests early in the morning so they could complete the results by the afternoon on the off chance that this information might provide insights that could help save Emily.
But on the day the test was performed, Dr. Kalos was in a bind, a family bind that any father could appreciate. His daughter was a student at a school in Massachusetts, a seven-hour drive from Philadelphia, and he had promised her that he would attend her first lacrosse game that Wednesday afternoon. He knew his being there meant a lot to her, so there was no way he was going to miss it, but he was also very concerned about Emily. The night before, he instructed the lab technicians to send the results to him as soon as they got them. He slipped his iPad, the best device he had to view Emily’s results, into his backpack before he left for Massachusetts that morning.
As he was standing on the sidelines cheering his daughter, he heard the ping that announced an email from the lab. Dr. Kalos walked away from the game and opened up his iPad to assess the results.
“Holy moly,” he remembers saying when he saw them. The results showed that Emily’s CAR T cells were really revved up and strong. They had chewed through the steroids and continued replicating at a robust rate. The other thing that jumped out for Dr. Kalos was that Emily’s blood had a very high level of interleukin 6 (IL-6) protein, a protein involved in inflammation, usually associated with other immune cells and, at the time, not associated with CAR–T cell therapy.
Dr. Kalos immediately forwarded the lab results and his interpretation to Drs. Grupp, June, and David Teachey, another specialist in leukemia who has his office near Dr. Grupp. In the minutes before they all jumped on a conference call, the doctors were frantically trying to chase down what this elevated level of the IL-6 protein meant to Emily’s immune system, searching scientific studies, and trying to find other doctors who had addressed this issue.
On a call Wednesday afternoon, Dr. June sounded very
