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COLUMBUS, Ohio — Two days after getting an experimental cancer therapy last May, Max Vokhgelt spiked a fever of 105.2. Surprisingly, he and his doctors saw it as a good sign: It meant the specially engineered cells coursing through his body were doing their job, attacking the leukemia he had been battling on and off for seven years.

As expected, his fever subsided. From his hospital bed in St. Louis, Max, 24, phoned his grandmother, Alexandra Armstrong. “His voice was firm and energetic” in a way it hadn’t been for days, she said. “He said, ‘Bubba, my fever went down. I won. In five or six days, I will be cancer-free.’” It was the last conversation they ever had.

That night, Max began suffering seizures and became delusional. He lost consciousness and soon was put on a ventilator to help him breathe. Two days later, at 7:25 a.m. on May 24, he was declared brain-dead and the ventilator was turned off. His father, mother, younger brother, and a rabbi were at his bedside.

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The cause of death, according to medical records obtained by STAT, was swelling and widespread damage in the brain — a massive overreaction by the cells of the immune system, known as a cytokine storm — likely triggered by the experimental treatment. Max was the first patient to die in a closely watched clinical trial of CAR-T therapy developed by Seattle biotech company Juno Therapeutics. He would not be the last.

In their first interview, Max’s family told STAT that their grief is mixed with anger and a thirst for answers. His father, Michael Vokhgelt, said he had hoped his son’s death would lead to new insights and changes in the treatment that could protect other patients.

In particular, he is upset that Juno did not immediately disclose Max’s death — not to investors who were buying the company’s stock or to the public. By the time it did in July, the chief executive had sold more than $8 million of his stock — though the trades had been scheduled in advance — and two more patients in the trial had died. Two additional deaths occurred last month.

“First, I believed Max had died for science, but now I think he died for greed,” Max’s father said.

“Why did it take Juno almost six weeks from the time Max died to disclose his death?” he wondered. “Maybe if they had reported Max’s death and investigated right away, the other two patients wouldn’t be dead.”

The family has hired a lawyer and is considering legal action against Juno.

Christopher Williams, a Juno spokesman, told STAT in an emailed statement that deaths in cancer trials of very ill patients are, “unfortunately, not uncommon” and typically aren’t immediately announced. He said Juno reviewed the death and added, “We fully understand how difficult this is for the patient’s family. … We extend our sincere condolences to them.”

To date, 38 patients with leukemia have been treated in the trial, and Williams said the treatment’s efficacy is roughly what it was in an earlier study, when 82 percent of patients experienced at least temporary remission. “The challenge we face,” he said, is that “we have helped a number of patients with the product, but the safety signals are worse than we expected.”

Max’s story speaks to the hope and trust that desperately sick patients and their families are willing to place in new, experimental therapies — as well as their tendency to minimize the risks inherent in unproven treatments that scientists don’t fully understand.

“Max completely believed in the CAR T-cells,” said his girlfriend, Carrie Harshbarger. “He told all his friends: ‘I am so lucky, so privileged to get in this trial.’ I don’t remember him talking about the risk.”

Immunotherapies such as CAR-T are high-wire acts. They work by revving up the body’s immune system to fight the cancer, but the same hyperactive immune cells that kill cancer cells can sometimes turn against the patient, attacking organs, including the brain. For patients like Max, however, the risks may seem worth it.

For Max’s father, the death of his oldest son weighed especially heavily. Only two years earlier, while Max was in remission from his first bout with leukemia, another son, Max’s half brother Daniel, was diagnosed with a rare type of muscle cancer. He died nine months later, at the age of 11.

“As adults, we’re not supposed to lose our children,” Michael said. Yet in a span of 14 months, he lost two.

Max Vokhgelt - Juno
Michael Vokhgelt, Max’s father, in Columbus, Ohio, last month. Andrew Spear for STAT

Cancer visits, twice

Max loved math, chess, and theater and, like most teenagers, could spend hours playing video games. But in 2009, as he began his senior year in high school near Columbus, Ohio, he was strangely lethargic, coming home in the afternoon and immediately falling asleep.

His father, a Russian-born computer programmer for the state of Ohio, took him from one doctor and specialist to another but none of them could figure out what was wrong. Finally, doctors at the oncology clinic at Nationwide Children’s Hospital suggested a bone marrow biopsy — just to be sure.

The results showed that Max had leukemia, a cancer of the white blood cells. The good news for Max — if such news can be good — was that the cancer cells had not yet spread from the bone marrow, where they form, to the blood.

“The doctor told us the prognosis for children was pretty good,” his father recalled.

Three and a half years of chemotherapy did its job — but it also took a toll. Max suffered side effects that included a stroke and infections of the pancreas and appendix.

Meanwhile, he tried to live his life. He graduated from high school — but was too sick to attend his commencement. Six months later, he enrolled at Ohio State University, but the combination of school and chemotherapy eventually became too much. He dropped out, fell into a depression, and was briefly hospitalized.

Then a couple of good things happened. He stopped taking chemotherapy because he was considered cancer-free. And he met a girl.

An avid cook, Max volunteered with a group called Local Matters that taught families how to cook healthy food on a budget. One day, he found himself washing dishes with a young staff member, Carrie Harshbarger.

They went out for a drink “and the rest is history,” said Carrie. They stayed together for a year, memorialized in a scrapbook of selfies and other photos she put together. It wasn’t an easy time, however.

In 2014, his half brother, born to Michael and his second wife, was diagnosed with the muscle cancer. Daniel spent months at Nationwide Children’s. Max visited at least twice a week, staying overnight to relieve his father.

“They would talk a lot about cancer,” Michael said.

Daniel’s death hit Max hard. His grandmother remembers his anguish. “He told me that Daniel had said to him: ‘Max, you beat cancer. You’ve got to help me.’ And he said, ‘I couldn’t help him.’”

Max had recently rented his own apartment but didn’t want to stay there so he moved into an attic room in his Bubba’s home. A picture taken around that time shows Max sitting on a beach during a trip to Virginia, staring blankly outward.

In early 2016, Max went to the dentist for a checkup. Alarmed by his excessive bleeding, the dentist sent him back to the oncology clinic. This time the diagnosis came quickly: His leukemia was back. And this time chemotherapy didn’t stop it. Instead it caused Max to have a heart attack, a side effect that almost kept him out of the Juno trial.

Max Vokhgelt - Juno
Alexandra Armstrong, Max’s grandmother, shows a printout of his GoFundMe page updates about the Juno clinical trial. Andrew Spear for STAT

Fear, and then excitement

Michael Vokhgelt had lost one son; he was determined not to lose another. Standard chemotherapy didn’t seem to be working, and he liked the idea of using the resources of the body’s own immune system rather than flooding it with toxic chemotherapy drugs.

“I started asking about alternative therapies,” Michael said. “There was a whole bunch of immune therapy trials and CAR-T trials with success rates of 90 percent. It seemed very promising.”

In the CAR-T approach, doctors draw blood from the patient and extract his or her T cells, a type of white blood cell that attacks other cells that are infected with viruses or cancer. The T cells are then genetically manipulated and tagged with a protein that helps them home in on cancer cells. These souped-up cells are then infused back into a patient.

Three companies — Kite Pharma, Novartis, and Juno — have jumped into the lead in the race to develop CAR-T cells for treating blood cancers. Together, they have treated about 270 patients in clinical studies, with impressive results: 47 percent to 82 percent of patients in these trials have gone into remission, at least for a while.

But unleashing the immune system carries risks. Seven patients have died from brain swelling in Juno trials, along with at least seven more from other treatment-related causes in the first 30 days of the therapy, according to Williams, the company spokesman, though he noted that mortality is higher with conventional treatments for blood cancers. Kite this month reported three deaths related to its CAR-T therapy for lymphoma.

With Max in the hospital, Michael hunted for CAR-T studies, and Juno’s name rose to the top of his list. A new company, founded in 2013, it brought together executives who knew how to raise money with scientists at the leading edge of immune therapy. The Juno study the Vokhgelts set their sights on even had a name that suggested speed — the ROCKET trial. And speed was something the Vokhgelts desperately wanted.

Michael called or sent emails to several hospitals that were part of the study. Max was rejected by each one — except Washington University in St. Louis.

In April, father and son drove all night from Columbus for an 8 a.m. meeting with Dr. Armin Ghobadi, an Iranian-born blood cancer specialist and assistant professor at Washington University School of Medicine.

Ghobadi was candid with them: The biggest barrier to Max being accepted was the heart attack he’d suffered while getting chemotherapy. But after evaluating his heart and brain function and consulting a cardiologist, Ghobadi concluded that Max did not have a “significant, clinically relevant cardiac problem or central nervous system problem,” he told STAT in an email. Based on these findings, the doctor convinced Juno to accept Max.

“As his oncologist, I believed and I still believe that CAR-T cell therapy was his best available option for putting his disease back in remission,” Ghobadi said. He met with Max and his father for an hour to explain the benefits and risks of the treatment, carefully going over the informed consent form.

“Because of my experience, I don’t trust doctors in general,” Michael said. “But Dr. Ghobadi was one of the best doctors I’ve ever met in my life. He treated Max almost like his own son.”

Early in April, Max called his girlfriend, discouraged. He was in pain, was having trouble walking, and wasn’t sure he’d get into the trial. “It was the only time I ever heard him scared,” Carrie recalled.

She later visited Max for two days and pushed him around St. Louis in his wheelchair. They talked about everything and he confided that if he didn’t get accepted into the trial he would probably die because he had never responded well to chemotherapy.

Finally, on May 10, Max was admitted into the study. “It’s hard to express my excitement and relief through type but I’ll try,” he wrote on his GoFundMe fundraising page. He said he was taking 200 steps a day in physical therapy and would be home in seven to eight weeks.

Max moved into the hospital, and in the first five days, he was injected with two chemotherapy drugs designed to eliminate his existing T cells and make room for the new ones. Then, on day six, he received the experimental therapy: an infusion of CAR-T cells that had been drawn from his own blood a couple weeks earlier.

Then came the bout of fever, and his upbeat call to his grandmother. Max invited her to come to St. Louis with his mother, Jennifer, and he promised to show them around the city. He never got the chance.

Puzzlement at Juno’s response

Max’s father can’t understand why Juno waited so long to disclose his son’s death and went full speed ahead with the ROCKET trial — until two more patients died from similar cytokine storms in their brains.

Instead, on June 4, a week after Max’s death, Juno issued a press release announcing that the CAR-T product used in Max’s trial, JCAR015, was demonstrating “encouraging” and “impressive” results that would help it advance toward becoming the company’s first commercial product.

On June 9, Juno CEO Hans Bishop sold $4.2 million worth of his company’s shares. Three weeks later, he sold another $4.4 million. The company reported to regulators that these sales were preprogrammed, and Juno’s Williams said they were arranged “well before the deaths” and complied with government regulations.

Not until July 7 did Juno acknowledge that three patients had died and that the Food and Drug Administration was halting the trial. In a statement that day, the company said it believed the deaths were caused by a toxic interaction between the CAR-T cells and a chemotherapy drug called fludarabine that had been added to the treatment regimen.

By the end of the next day, Juno shares had fallen 32 percent.

The company conducted an internal investigation after Max’s death, and consulted with the FDA and independent drug safety experts before concluding that there was no reason to stop or change the trial, Williams said.

“By itself a single patient death does not necessarily signal that a trial is unsafe and therefore is not necessarily a reason to stop the trial, particularly when the treatment is saving the lives of other patients,” he said.

The reason the company made a public disclosure after the second and third deaths is that the FDA imposed a hold on the trial and the company was required under securities laws to announce the FDA’s action and its reasons, Williams said.

The company believed that fludarabine was the most likely factor in these three patients’ deaths, and apparently convinced the FDA of this as well. Five days after announcing the trial’s suspension, Juno said the drug regulator had given it the green light to resume the clinical trial — an unusually fast turnaround time that was crucial for Juno’s hopes to be the first company to bring a CAR-T therapy to market. Then, on Nov. 23, the company issued another release: Two more patients had died — and neither had received fludarabine.

The ROCKET trial is once again on hold and the future for Juno’s therapy is cloudy.

Max Vokhgelt - Juno
Carrie Harshbarger, who was Max’s girlfriend, hugs his step-grandfather, Ken Armstrong, while his grandmother, Alexandra Armstrong, stands to the side. Andrew Spear for STAT

Struggling with grief

Six months after Max’s death, sadness still envelops his father, present in every movement and facial expression. Sitting at the dining table of his home in suburban Columbus, he speaks haltingly, in a baritone so soft it is sometimes barely audible, his face buried in his hands.

He has considered going to grief counseling or support groups, but it doesn’t feel right; he thinks the experiences of other participants would be too different. He wonders about the parents of the other young people who died in the ROCKET trial and would like to speak with them.

“I feel bad for those parents. I think we could help each other,” he said. “Grief is a thing — sometimes you can work through it alone; sometimes you can’t.”

Michael paused and his 3-year-old son, Lyonya, a calm, quiet boy who has his father’s round face and blond hair, walked over and stroked his father’s cheek. Michael kissed his hand tenderly and they spoke for a moment in Russian.

Asked how he keeps going, after the loss of two sons, he looked over at Lyonya. “This guy helps,” he said. “He’s my savior.”

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