“I’m a clinical trials junkie!”
So says Brian Koffman, M.D., a 73-year-old retired family physician from Claremont, California, who saw his personal and professional life upended when the doctor became the patient.
Back in 2005, Dr. Koffman spotted lumps on the back of his neck. Running his own blood tests (“I know,” he says, smiling, “any physician who treats himself has a fool for a patient”), he noticed an elevated lymphocyte count. Further testing determined that Dr. Koffman had chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, affecting some 20,000 people each year.
Dr. Koffman’s medical team suggested doing — nothing. At least for now. But the “watch and wait” approach didn’t sit well, especially when, a short time later, Dr. Koffman saw red spots on his legs and his platelet count began to drop, a sign of his cancer going on the attack. “I was getting a lot of bad advice,” he recalled. He was also getting worse and needed emergency surgery to remove his spleen in an attempt to halt the platelet drop.
Dr. Koffman then briefly, and unexpectedly, went into remission. He used the time to dive into the research and plot an aggressive attack, which took him from one cutting-edge treatment to another. A stem cell transplant in 2008 performed by City of Hope’s Stephen J. Forman, M.D., director of the Hematologic Malignancies Research Institute, brought a few months of relief. Three years later, Dr. Koffman literally talked his way into a clinical trial — buttonholing the chief investigator in a hallway of the American Society of Hematology conference, who enrolled him in a study for the targeted therapy drug ibrutinib (approved by the Food and Drug Administration in 2014). Dr. Koffman moved to Ohio to participate in the trial. Good call. Ibrutinib put him in remission for seven years.
Facing a CLL Relapse
When he inevitably relapsed, Dr. Koffman headed to Seattle for another “latest and greatest” innovation: a trial of CAR T cell therapy — in which his immune cells were reengineered to seek out and destroy cancer — combined with ibrutinib. He suffered intense side effects, including cytokine release syndrome (CRS), but nevertheless achieved remission, this one lasting five years.
Along the way, Dr. Koffman began to blog, hoping that others would benefit from his experiences. That effort turned into a career pivot and a brand new organization: Dr. Koffman founded and directs the nonprofit CLL Society. Experts in the field know all about him, and they are impressed.
“He is very informed, and he has made a huge contribution,” said Alexey Danilov, M.D., Ph.D., associate director of City of Hope’s Toni Stephenson Lymphoma Center and a world leader in lymphoma and CLL research. “His is the strongest voice for patients with CLL.”
Drs. Danilov and Koffman met through the society and hit it off immediately. In 2020, when Dr. Danilov joined City of Hope, Dr. Koffman asked him to be his hematologist. “I really like him,” said Dr. Koffman. “I’m impressed with his research, but also with his sense of humor. He is very caring, wicked smart, plus he has the ‘three As’: he’s able, affable and available.”
And now they are research partners.
When Dr. Koffman’s disease returned in 2022, Dr. Danilov enrolled him as the first participant in a new trial which, if successful, may revolutionize CLL treatment. Joined by colleagues at dozens of institutions around the world, Dr. Danilov is examining a unique bispecific immunotherapy drug called epcoritamab.
Like some monoclonal antibody drugs, epcoritamab binds to the CD20 marker on a patient’s diseased B cells, which makes them better targets for the immune system’s T cells to destroy. But that’s not always enough. So epcoritamab packs a powerful second punch. It also binds to the CD3 marker on those T cells, pulling them closer to the B cells for a more efficient attack.
'This is a first-of-its kind treatment for CLL. It takes a very novel approach that has not been studied in the past. It is state-of-the-art, one-of-a-kind.'
Alexey Danilov, M.D., Ph.D.
“This is a first-of-its kind treatment for CLL ,” Dr. Danilov says. “It takes a very novel approach that has not been studied in the past. It is state-of-the-art, one-of-a-kind, very different from other CLL treatments.”
And it’s working.
The trial is still in Phase I, but Dr. Danilov already has good news to share. He reported on the study’s latest results at the American Society of Hematology’s annual conference in San Diego Dec. 7 to 10.
“Epcoritamab is effective,” says Dr. Danilov. “We are seeing an overall response of 70% and a complete response [full remission] in 40% of cases.” This is especially significant because the study participants are mainly “double refractive” — people who’ve experienced multiple relapses after other treatments failed. “That’s a very difficult population to treat.”
Dr. Danilov also believes the risk of CRS — essentially the immune system kicking into overdrive and harming the patient — can be mitigated with a three-stage “step-up” approach: starting with a low dose of epcoritamab in week one and gradually increasing to full dosage by week three, allowing the body to adapt.
Now in CLL Remission
One year into his participation, Dr. Koffman is in full remission. His maintenance plan is simple: a “non-event,” as he calls it. Once a month he visits City of Hope for tests, bloodwork and his epcoritamab injection, “a 30-second shot.” Within an hour he’s headed home. He’s had no major side effects since the first five “awful” weeks of the trial when researchers were still figuring out the proper dosage and countering CRS with steroids. Dr. Koffman pushed through, continued working and reached the other side.
'He is very caring, wicked smart, plus he has the "three As": He’s able, affable and available.'
City of Hope patient Brian Koffman, M.D., on his physician Alexey Danilov, M.D., Ph.D.
He is grateful to everyone involved but especially to his No. 1 caregiver, his wife Patty, whom he calls “the hero of this story” who is “on duty 24/7” seeing to his care.
And he knows he’s not done. Like his previous treatments, Dr. Koffman expects this one to falter one day. “This is chess,” he says. “You have to think one or two moves ahead. I’m already planning my next therapy.”
On the other hand, maybe, just maybe, epcoritamab is the one that will last. Dr. Danilov is optimistic.
“It’s still very early,” he says. “And we need more data,” especially from patients at earlier stages of CLL, whose immune systems have not been ravaged by multiple therapies.
“But I think it’s possible some users of epcoritamab will see long-term results."
Main image: Brian Koffman with his wife Patty.