Published on June 30, 2020
Can a Vaccine Prevent a Recurrence of MCL?
Researchers at Stanford University have developed a method for creating a vaccine from a patient’s own tumor cells that could prevent the blood cancer mantle cell lymphoma (MCL) from recurring after being treated.
A phase I/II clinical trial, published in the June 19 issue of the Journal of Experimental Medicine, resulted in 89 percent of the patient participants remaining free of minimal residual disease (MRD) for the year of the experiment, meaning their blood contained too few cancer cells to form new tumors.
"That surpasses previously reported MRD-free rates for MCL patients," said Stanford professor and research leader Dr. Ronald Levy in a press release announcing the findings.
MCL occurs in about 6 percent of all non-Hodgkin lymphoma patients and is most common in men 60 years and older, according to the Lymphoma Research Foundation. It gets its name because the tumor cells originally come from the “mantle zone” of the lymph node. It is often diagnosed as a late-stage disease and is usually present in the gastrointestinal tract and bone marrow.
Treatment is usually a combination of chemotherapy and immunotherapy, often accompanied by a stem cell transplant to help the body form new, normal, healthy blood cells. But the cancer often recurs, and the average survival time for MCL patients is 5-7 years.
“It is one of the most difficult lymphomas to treat,” said Dr. Michael Wang, a professor of lymphoma and myeloma at MD Anderson Cancer Center in Houston, Texas. He spoke with Patient Power Co-Founder Esther Schorr at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.
“Because it's rare, in the past the studies are not as much because there's not so many patients affected, not a huge margin, not a lot of investment, but mantle cell lymphoma is a dead lymphoma… deadly. Oftentimes patients do not survive.”
Stanford’s vaccine approach followed previous research conducted by Levy and his colleagues on mice. In those experiments, tumor cells from the rodents were infused with CpG oligonucleotides, short fragments of DNA that mimic bacterial DNA. Those tumor cells prompted an immune response when they were injected back into the mice.
"Guided by these preclinical results, we designed a phase I/II clinical trial to evaluate the therapeutic potential of a similar vaccination approach as an additive to standard stem cell transplantation for patients with MCL," Levy said.
In the human trial, 47 patients who were in remission following standard immune and chemotherapies were vaccinated with their own CpG-infused tumor cells. The patients' immune cells were then collected and stored while the participants received a stem cell transplant. Then, the immune cells were transferred back into the patients.
Levy’s team reported the vaccination regimen appeared to have no side effects beyond those normally associated with stem cell transplants.
Of the patients, 40 percent formed immune cells capable of directly attacking and killing cancer cells. These patients went longer without any recurrence of MCL, even if their tumors contained genetic mutations associated with a poor prognosis.
"Overall, our data demonstrate that the addition of a CpG-activated whole-cell tumor vaccination followed by adoptive transfer of vaccine-primed immune cells to the treatment of MCL is feasible, safe, and can induce immune responses that are associated with a superior clinical outcome," Levy said.
At the ASH meeting, Dr. Wang, who has been treating MCL for 20 years, told Schorr that MCL therapy has evolved greatly from chemotherapy to targeted therapies. He noted there are now several FDA approved oral medications for MCL, including lenalidomide (Revlimid), ibrutinib (Imbruvica), zanubrutinib (Brukinsa) and acalabrutinib (Calquence). Calquence has been shown to have an 80 percent response rate, he said. CAR T-cell therapy has also been shown to benefit MCL patients who are not responding to other treatments.
“I'm very, very proud of what we, my team has already done, but I am especially happy for our patients because they no longer have to get an IV line and lose hair, fall down, cause infections,” Wang said. “So novel therapies, not only are they much less toxic, they are very, very powerful.”
Looking for more information about MCL? Sign-up for e-news and we’ll send it directly to your inbox.
- Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma
- Early clinical trial supports tumor cell-based vaccine for mantle cell lymphoma
Recommended for You: