cord blood transplant

Third treatment’s the charm for lymphoma patient

After relapsing twice, Juan Yee finds renewed hope in mosunetuzumab, a bispecific antibody therapy recently approved by the FDA

When postal worker Juan Yee was told that his non-Hodgkin’s lymphoma had relapsed for a second time in 2018, he was ready to let nature take its course. 

“I couldn’t go through chemo again,” says Yee, 49, who was first diagnosed with Stage 4 follicular lymphoma in 2012, with extensive enlarged lymph nodes and bone marrow involvement, and had his initial relapse in 2016, experiencing swollen lymph nodes, soft tissue masses, weight loss, fatigue and persistent night sweats. “It was painful and I was tired. I was done.”

But thanks to one last try with an experimental drug that at the time was in clinical trials, he’s been in complete remission for nearly five years now. That drug, a bispecific antibody made by Genentech and called mosunetuzumab, was just approved by the Food and Drug Administration for use in patients with relapsed or refractory follicular lymphoma, the most common slow-growing form of non-Hodgkin’s lymphoma, after clinical trials like the one Yee participated in showed high response rates. Eighty percent of patients responded positively to the treatment, and a majority maintained responses after 24 months. A complete response rate was achieved in 60% of patients.

Follicular lymphoma accounts for about 1 in 5 cases of non-Hodgkin’s lymphoma. It typically responds well to treatment, but tends to relapse after periods of remission. The disease usually becomes harder to treat each time a patient relapses, and early progression can be associated with poor long-term prognosis. It is estimated that, in the United States, approximately 13,000 new cases will be diagnosed in 2023, and more than 100,000 people are diagnosed with follicular lymphoma each year worldwide.

A Persistent Disease

Yee, who lives in San Diego, remembers the first signs of non-Hodgkin’s lymphoma clearly: swollen lymph nodes and fatigue. But as a child, he often dealt with similar symptoms from recurrent infections, so he brushed them off. 

“I was trying to be macho and kept working a lot, but then more started happening,” he said. “My appetite disappeared, I felt weak, I was having night sweats. But I really got scared when I woke up one day and my testicles were really swollen.”

He immediately went to see a friend who is a doctor in Tijuana, where Yee, whose parents are Mexican and Chinese, was born and raised until the age of 14. Within a few days, his friend broke the news that the lab tests revealed cancer, and urged him to see his doctor in the States. 

“I was 38, the first person in my family to be sick,” Yee recalls. “My three sons were still young then, so it was scary. But I tried to be positive, and my whole family really supported me.”

Nonetheless, the chemotherapy treatments were rough, with many side effects like constipation, heart burn and hair loss. Then, in 2016, when his lymph nodes started swelling again, Yee had to repeat the whole experience. So, when cancer struck for a third time just two years later, he felt like he was at the end of his rope. 

“My doctor recommend that I do a stem cell transplant, but warned that it was risky,” remembers Yee. “I didn’t want to put my family through all that. I was depressed and just thought ‘This is it. I’m not doing anything else.’”

A Different Approach

Shortly after his third diagnosis, Yee’s sister called to tell him that a celebrity was on television celebrating that he was five years cancer-free after battling the same disease plaguing Yee — non-Hodgkin’s lymphoma. Yee took a chance and messaged the person on Instagram. 

“Within minutes he replied,” he says. “So I asked him what he was doing to stay healthy, and he told me about his diet and that he was using cannabis oil. He said good luck, and that was that. But I got excited to try something else. My friend got me some cannabis and I prayed a lot. I decided to go see my doctor again.”

It was at this follow-up appointment that his oncologist recommended he meet with Elizabeth Budde, M.D., Ph.D., associate professor in City of Hope's Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation, who was running the mosun trial at City of Hope.  

Meet Hematologist Elizabeth Budde, M.D., Ph.D.
Elizabeth Budde, M.D., Ph.D.

“My doctor said he had read about the new medication they were testing at City of Hope, and it seemed really promising. It sounded too good to be true, but Dr. Budde is Chinese, so I decided to go see her,” Yee says with a laugh. 

From his first moments at the hospital with his wife, Rocio Murillo, Yee says they both really liked City of Hope, Budde, and the way he was treated.

“I remember she explained everything to me about how the medication was going to help me, not hurt me,” says Yee. “She told me my good cells would learn how to fight the bad cells. And that I probably was not going to have chemotherapy-type side effects, I wasn’t going to lose my hair.”

That’s because unlike chemotherapy, which can damage healthy cells as it is killing cancer, mosun helps amp up the body’s immune response to an invader like cancer. The therapeutic employs bispecific antibodies that act on two cellular targets: the CD3 protein on T cells, an immune cell that can help in the fight against cancer if engaged, and CD20, a protein commonly found on lymphoma cells.
 
“The good and bad cells are pulled together, with mosunetuzumab serving as a kind of bridge,” Budde explains. “Being in such close proximity allows the now activated immune T cells to specifically recognize, attack and eliminate the lymphoma cells.”

This all sounded really good to Yee, but his real moment of conviction came in the waiting room before his first clinical trial treatment appointment when the celebrity he'd connected with on Instagram walked through the doors to receive a follow-up treatment for his non-Hodgkin’s lymphoma. 

“I was so happy,” says Yee. “I was like, this is God telling me this is what you need to do. I mean, he answered my texts and then on my first day of treatment he's here!”

Yee says that compared to his other treatments, the clinical trial was a breeze, with just minimal fatigue as the only side effect, along with short-term spikes in his blood pressure during the treatment. 

Looking to the Future

“Thanks to Juan’s participation along with other brave patients, our study demonstrated that a pure immune therapy based on bispecific T cell-engaging technology is proving to work very well with high response rates — and safely — in blood cancer patients who need more effective therapies and with fewer side effects,” says Budde. “Mosunetuzumab is a highly efficacious therapy, showing deep and durable responses for patients whose follicular lymphoma has relapsed or is no longer responding after two prior lines of therapy.”

“This [FDA] approval is a significant milestone and signifies the beginning of a new treatment modality for lymphoma, since mosunetuzumab is the first bispecific antibody approved for lymphoma,” Budde continued. “At City of Hope, the integration of scientific research and clinical trials allows us to deliver groundbreaking science and treatments from laboratory to patient. Mosunetuzumab could change the way advanced follicular lymphoma is treated.”

Still, Yee admits to some fear going into the trial, with images of lab rats running through his head. 

“I remember thinking ‘Am I gonna grow another leg or three eyes?’” he says. “But when I went to the doctor, she gave me so much confidence that I wanted to try it. I went from doing nothing to having hope again.”

Plus, he learned during that time that his oldest son, Alejandro, was going to become a father. Now, nearly five years later, Yee is enjoying his growing family, and his third chance at life. He said he’s become more patient and closer to his already very close family. And he’s feeling healthy and thankful for his chance to share his story. 

“When I was going through treatments, I would ask God why this was happening to me,” says Yee. “And now I think it’s so that I could do this trial and help other people. I can share my positive experience and let people know they shouldn’t give up. Have faith.”