CAR-T-cell therapy opens up the world to lymphoma survivor

Marcus Humphrey had one of the worst cases of lymphoma that Brian Hess, M.D., had ever seen.

 

A full-body scan showed Marcus’ body peppered with lymphoma, no nook or cranny untouched. The lymphoma, which showed up as an eerie white emptiness on the scan, ranged from dots and spots to blotches and spreading stains.

"Mr. Humphrey had a large lymphoma burden noted on his scans at diagnosis, but what was more concerning was how resistant his disease was to chemotherapy and how quickly it was growing with each relapse,” explained Hess, a physician-scientist who specializes in blood cancers at MUSC Hollings Cancer Center. “This leads to enormous challenges when trying to collect a patient’s cells for CAR-T-cell therapy and waiting for them to be manufactured.”

Two rounds of different chemotherapy protocols failed to control the cancer. Failed chemotherapy is a requirement before CAR-T-cell therapy can be offered because it is an intensive therapy with the possibility of serious side effects. The therapy involves removing a patient’s T-cells, engineering them to develop a laser-like focus on a protein found on the surface of the lymphoma cells, and then returning the CAR-T-cells to the patient’s body to do their work.

"They were really struggling with the idea of doing CAR-T. They said his tumor load was so heavy,” said Marcus’ wife, Mary. “Even right up until the last minute, Dr. Hess really struggled with whether or not to do CAR-T, because he felt like it may not provide him any benefit – or worse could kill him. But we felt like the lymphoma was going to if he didn’t at least try.”

Lifelong educators

 

Marcus and Mary met when she started working at the same organization that he did, working with children with disabilities.

“Everybody I met said, ‘Oh, you’re going to love Marcus. Oh, you get to work with Marcus.’ Marcus, Marcus, Marcus, Marcus. So by the time I met him, I was like, ‘Who is Marcus?’” she said.

When they finally met, one of her male teenage charges introduced her as his “girlfriend.”

“Can’t be your girlfriend,” Marcus said recently, as he and Mary told the story together; their words tumbling over each other in the way of married couples of almost 47 years.

“Marcus said, ‘She’s not your girlfriend. I’m going to marry her,’” Mary recalled. “It’s like, ‘Yeah buddy, in your dreams. In your dreams.’”

Marcus mimed casting a fishing line and reeling it back in.

“She’s on the hook,” he said.

She was. Eventually the two went on to settle in Beaufort, South Carolina, to have four children and to become teachers. Mary taught kindergarten and Marcus taught fifth grade.

“I just absolutely love it,” he said. “They all come in with this attitude that they know everything. They don’t need a teacher. I don't argue the point. I just know there’ll come a day when they’re going to look up and say, ‘Mr. Humphrey, can you help me with this?’”

‘Dad, what is going on with your neck?’

In December 2021, the Humphreys were preparing for a trip to the Keys with family and then to California to visit their eldest son. As they were preparing to leave for Florida, Marcus felt an odd knot on his neck. He asked the rest of the family if they could see it, but it wasn’t really visible.

They went to Florida as planned, but Mary noticed that something was off.

“He was not himself. He's usually very active – swimming, fishing, in with the kids a lot – and he pretty much sat on the beach with me, which wasn't typical,” she said.

By the time they returned to South Carolina for Christmas dinner, their daughter-in-law, a nurse, noticed the lump and told them that he should have a specialist look at it. But their trip to California was next, and they decided to do that first.

“So we went out to California, and the very first thing our oldest son said, before he even said hello to us at the airport was, ‘Dad, what is going on with your neck?’ So it had grown that fast,” Mary said.

 

Back home in South Carolina, the Humphreys saw an ear, nose and throat specialist, who initially thought it might be a cyst.

Marcus was ready to believe that – he didn’t want to think it could be something serious. He searched online for information about cysts, and he recalled having a cyst as a child, so he figured that was probably the correct diagnosis. Mary, though, knew it wasn’t a cyst. So did the doctor as soon as Marcus returned for a follow-up visit and the lump had grown again. And when the doctor looked at the results from the CT scan he had ordered, he sprang into action.

“He started calling oncologists. Neither of us could get anybody to even answer their phone,” Mary said. “He finally got somebody who said he could see Marcus on the 19th – and this was the 12th I believe – and his response to him was, ‘I’m afraid if we wait till the 19th this man might not be here.’”

That was the moment when Marcus realized the seriousness of the situation.

Finally, Marcus got to Hollings for a core biopsy. Afterward, the doctor advised him to get to an emergency department – whether in Beaufort or Charleston – to have someone assess his kidney function. Lymphoma frequently affects the kidneys, and Marcus’ numbers weren’t good.

The Humphreys decided to go to the Emergency Department at MUSC Health, and from there, he was admitted to the hospital. That night, the health care team began to administer chemotherapy.

Thus began a terrifying journey as Mary watched the effects of the treatment take its toll. Ultimately, Marcus, who was diagnosed with both diffuse large B-cell lymphoma, a type of non-Hodgkin lymphoma, and follicular lymphoma, went through two series of chemotherapy treatments.

“He lost 65 pounds almost immediately. Lost all his hair, every bit of eyebrows, eyelashes, everything,” Mary said. “He looked like a Holocaust survivor. He could hardly walk. He was still in a lot of pain. The lymphoma had gotten in behind his eyes and was pushing his eye.”

CAR-T-cell therapy

CAR-T-cell therapy was first approved by the U.S. Food and Drug Administration in 2017. The idea behind the therapy is to supercharge the patient’s immune system against the cancer.

T-cells, a type of white blood cell that is part of the immune system, are removed from the patient’s body. In the lab, a CAR, or chimeric antigen receptor that specifically targets a protein found on the surface of the lymphoma cells, is added to the T-cell. The cells, now called CAR-T-cells, are then returned to the patient’s body. With the CAR attached, they’re super focused on finding and destroying the lymphoma cells.

The therapy is expensive and highly specialized – not every hospital is equipped to offer cellular therapies. It also comes with the chance of serious side effects, including a cytokine release storm (CRS), which happens when the CAR-T-cells expand and proliferate, attaching to the lymphoma and resulting in massive numbers of cytokines being released into the bloodstream, causing symptoms that can include fever, trouble breathing, and low blood pressure, along with neurologic side effects.

CAR-T-cell therapy doesn’t work for everyone. But when it does work, the effects can be remarkable.

"The goal for every lymphoma patient that receives CAR-T is to get into a complete remission, meaning there is no evidence of disease on your scan,” Hess said. “If this is the case after CAR-T, the majority of these patients never experience a disease relapse, and we believe are likely cured.

“If a patient does not achieve a complete remission, however, or if they relapse after a complete remission, these patients typically have a terrible prognosis,” he continued. “So CAR-T is a very ‘all or nothing’ proposition to offer to patients with aggressive lymphoma. The patients and caregivers have so much on the line.”

 

Marcus doesn’t remember the immediate aftermath of the CAR-T treatment. He almost immediately ended up in the intensive care unit because of the CRS and neurotoxicity side effects. He has fuzzy recollections of his hospital stay after he was returned to the cancer floor from the ICU.

“I remember being so frustrated with not being able to respond to some simple questions – first and last name, date of birth. And here I was a teacher, and I couldn’t count backwards from 100 to zero by tens,” he said.

Mary recalls the kindness and positivity of the staff they encountered throughout this time.

“They were so encouraging. One of the nurses was getting married, and every day she was in there, encouraging us. We told them, ‘We’re praying for all of you’ and they were praying for us. It was just a really sweet, sweet group of people that were just unbelievably supportive and very positive,” she said.

Slowly, Marcus began to recuperate. Physical therapists, occupational therapists and music therapists worked with him in the hospital. He received the CAR-T-cell therapy in May, and by June was discharged to stay at the American Cancer Society’s Hope Lodge, located across the street from Hollings. Mid-July, the Humphreys returned home.

 

At home, Mary insisted that Marcus use the community pool regularly.

“That was huge because he started swimming and using his arms, and he was able to get out and stop using the walker fairly shortly after he started getting in the pool again. So that was another big leap,” she said.

“I felt like it was miraculous, just to see how bad he had been and then the speed with which he seemed to be getting around. It’s just remarkable,” she said.

At Christmas, one year after he first noticed the odd little knot on his neck, Marcus was once again surrounded by family.

“I didn't care if I didn't open a single package. All I needed was sitting around me,” he said.

Marcus still has side effects from the treatment. He hasn’t been able to return to playing the guitar, for example, because he can’t touch his fingers to his thumb on his left hand. He’s made progress though – at first, he couldn’t bend his fingers at all, and now he can almost make a fist – and he continues to work on his occupational therapy exercises.

 

He and Mary aren’t letting those side effects slow them down.

Now, almost one year after his CAR-T treatment, the couple is preparing for a five-month trip through southern Europe and Israel, thanks to a college friend’s gift of airline miles.

It’s a trip they never could have envisioned last spring or summer when Marcus was wracked with pain or unconscious in the ICU. His doctors have blessed it, making special arrangements for him to have his necessary medication.

"It was pretty amazing for all of us to hear their vacation plans,” Hess said. “Not too long ago, he was close to a hospice conversation. Now he is taking every advantage possible to live life to the fullest – this is the goal for all patients receiving CAR-T – to give them their life back as it was prior to lymphoma.”

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