Michael Gikher joined a clinical trial led by Dr. Lia Palomba testing a CAR T cell therapy for resistant mantle cell lymphoma. She says the treatment, recently approved by the FDA, “will offer some hope for patients who in most cases would have reached the end of the line.”
Mantle cell lymphoma (MCL) is a rare and sometimes ruthless form of non-Hodgkin lymphoma. Even when treatment appears to be successful, the cancer often returns and is difficult to cure.
A new therapy has been approved by the U.S. Food and Drug Administration (FDA) for these most challenging cases: lisocabtagene maraleucel, or Breyanzi®. The approval was based on results from a clinical trial led by MSK hematologist-oncologist Lia Palomba, MD.
“We now have a good option for a type of lymphoma that has been very difficult to treat when other therapies fail,” Dr. Palomba says. “This is urgently needed because the disease grows more resistant every time it comes back.”
Lisocabtagene maraleucel is a chimeric antigen receptor (CAR) T cell therapy. This form of immunotherapy involves removing T cells from a patient and outfitting them in the lab with receptors that recognize specific targets — known as antigens — on the surface of a cancer cell.
This type of CAR T treatment targets an antigen called CD19, a strategy that was first proposed in 2003 by MSK physician-scientist Michel Sadelain, MD, PhD, a pioneer in CAR T cell research.
Clinical Trial Results for Lisocabtagene Maraleucel
The trial tested lisocabtagene maraleucel in 88 patients with relapsed or resistant MCL who had already received at least two kinds of therapy, including a targeted therapy called a Bruton’s tyrosine kinase (BTK) inhibitor.
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83% of patients responded to the treatment, meaning it reduced the cancer;
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72% of patients had a complete response to the treatment, meaning the cancer disappeared completely;
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The median progression-free survival (time until the cancer began growing again) was 15.3 months.
- Side effects were tolerable and reversible in most cases.
The trial had no control group, meaning it did not compare lisocabtagene maraleucel to another standard treatment. But Dr. Palomba says the CAR T cell treatment worked well in patients who had already received many lines of therapy — up to 11 in some cases. In those patients, standard therapy didn’t work for long.
“Approval of this treatment will offer some hope for patients who in most cases would have reached the end of the line,” she says.
Patient Successfully Treated With Lisocabtagene Maraleucel
For Michael Gikher, the CAR T treatment proved to be a lifeline. When he was first diagnosed with stage 4 mantle cell lymphoma in 2013, he did not waste time worrying. A taxi driver living in Brooklyn, he had the no-nonsense outlook of his upbringing decades earlier in Ukraine.
“I’m not a person who gets discouraged,” he says. “We are tough people, and nothing bothers us much. I just asked my personal physician, ‘What are we going to do about it?’ He said, ‘You have to find good doctors,’ and he gave me a few names.”
After talking it through with his sons, Michael chose MSK medical oncologist and lymphoma specialist Andrew D. Zelenetz, MD, PhD, because of his expertise. Dr. Zelenetz recommended a very strong chemotherapy regimen.
“He told us that’s what he would give to someone in his own family,” Michael recalls.
For six years, the chemotherapy held the cancer at bay. Michael sold his taxi, moved to Florida, and began enjoying retirement. But five years ago, a scan revealed a tumor in Michael’s spleen. Dr. Zelenetz prescribed more types of therapy, but they failed to slow the cancer down.
In the past, Michael’s prognosis would have been dim. But Dr. Zelenetz proposed that Michael join Dr. Palomba’s clinical trial. Michael did not hesitate.
“I’m the kind of person who trusts my doctor,” he says. “Whatever he says, I go for it. I want to stay alive.”
How the CAR T Immunotherapy Works
In 2020, Michael’s T cells were extracted, modified to attack the MCL cells, and then infused back into his body. The experimental treatment was demanding, and Michael had to stay in the hospital about a month to monitor side effects. But over that time, CT scans showed the cancer began to subside, and then it disappeared.
The results were undeniable.
“If anybody asks me ‘Where should I get treatment?’ I tell them, ‘Don’t go to a doctor just because they are close by and it is most convenient,’” Michael says. “Go for the knowledgeable doctor who has huge experience dealing with this all the time. The whole world knows MSK is the best place to go with cancer problems.”
Three and half years later, the cancer has not returned. Michael travels from Florida to New York for checkups with Dr. Palomba and Dr. Zelenetz once or twice a year.
His only notable lasting side effect has been low white blood cell counts — common among CAR T cell recipients and treated with occasional injections. Although it is too early to say if this treatment strategy will result in a real cure for some patients (meaning the disease will never come back), Dr. Palomba says that Michael’s odds of a relapse are low considering it has been more than three years since his CAR T cell treatment.
Now 72, Michael is enjoying time with his wife, three sons and six grandchildren — all of whom live close by. His wife is now facing her own illness, and he’s grateful to be able to care for her.
“I’m very happy to be alive and that the treatment seems to still be working,” Michael says.
Giving Lisocabtagene Maraleucel Sooner
Dr. Palomba says the positive results seen in people like Michael support giving lisocabtagene maraleucel earlier to patients with high-risk features of the disease — rather than waiting until other treatments fail. This CAR T cell treatment could possibly be part of a second-line or even first-line therapy for selected patients.
Lisocabtagene maraleucel has already been approved by the FDA for three other distinct subtypes of non-Hodgkin lymphoma. Dr. Palomba’s research played a major role the treatments approved for two of these types — diffuse large B cell lymphoma and follicular lymphoma.
The approval for mantle cell lymphoma marks another landmark achievement for CAR T cell therapies originating at MSK, where lessons in the lab and the clinic are shared efficiently, creating a unique ecosystem of discovery.
“This treatment was born out of investigations in MSK labs that we have been able to adjust and modify in the clinic,” Dr. Palomba says. “I have led trials, along with MSK hematologic oncologist Jae Park, MD, testing different iterations of the CAR T cells so they will be more persistent and effective. Fundamentally, these therapies have completely changed the outcome of people with aggressive lymphomas.”
