Published Aug 28, 2019
It’s not very often that one of the most prestigious cancer centers in the country says that it has developed a treatment with “curative potential.” That’s what’s just occurred as researchers from the Dana-Farber Cancer Institute, which is associated with Harvard, said they’ve tested a treatment combination that may actually work to cure some people with Chronic Lymphocytic Leukemia.
The new treatment is a combination of drugs called “iFCR,” developed under a team led by Dr. Matthew Davids, Associate Director of the CLL Center at The Dana-Farber Cancer Institute.
“Our study establishes iFCR as an option to consider for young, fit CLL patients who desire an intensive therapy [in a first treatment] with the potential to lead to durable remission,” Dr. Davids told SurvivorNet. Durable remission is physician speak for an exceptional outcome.
CLL usually occurs in older people. The average age at diagnosis is about 70 years old. It is rare for CLL to occur in people under age 40, and it is even more rare in children.
The drug combination was mostly effective for somewhat “younger” patients with this disease, which in this case means 65 years old or younger.
The new drug is a mixture of what’s called “chemoimmunotherapy” and what’s known as a “targeted drug.”
Chemoimmunotherapy itself is a mixture of traditional chemotherapy, which kills cancer cells along with many other cells in the body, and immunotherapy, which uses the body’s own immune system to fight the disease.
In this instance, doctors have mixed chemoimmunotherapy with targeted therapy drugs, which get in the way of specific molecules needed for cancer growth, rather than by interfering with all rapidly dividing cells (which is how chemotherapy works).
While the drug may have the potential to help a lot of people, it probably won’t totally replace the current treatment method. “We would not consider it to be a new standard of care until it is compared head-to-head with current approved standard regimens, which are also highly effective,” Dr. Davids said in an interview.
Because CLL is a disease that develops slowly, many people live for years without symptoms. That is also why it is hard to screen for the disease, and doctors must use a variety of blood tests to confirm diagnosis.
In the study just released, the drug combination was given to 85 patients with CLL, with a median age of 55.
The study looked at CLL patients who had what’s called an “IGHV mutation,” which is associated with a higher probability that chemotherapy will work for a longer period of time. They also looked at people without the mutation, whose chemotherapy usually lasts for a shorter period of time.
The patients, who had not undergone prior treatment for CLL, received the targeted drug for seven days, and then for up to six consecutive 28 day cycles, they received chemoimmunotherapy alongside targeted therapy.
33 percent of patients had a complete response to the cocktail, with “undetectable minimal residual disease” in bone marrow two months after treatment. That means that only tiny, imperceptible amounts of the disease may have remained after the treatment.
84 percent of patients at any time during the study had a response of undetectable minimal residual disease in bone marrow.
Initial treatment options for CLL depend on age
CLL cannot be cured but there are several options when it comes to the initial treatment. According to Dr. Davids, the standard treatment route is currently some form of chemo-immunotherapy. Typically, a chemo-immunotherapy regimen is given as initial therapy for six months at a time. Any treatment lasting longer than six months is difficult to tolerate.
What are the current initial treatment options for CLL? Dr. Matthew Davids, Associate Director of the CLL Center at Dana-Farber Cancer Institute says the options depend on the patient’s age
Dr. Davids says for patients under age 65, the go-to chemo-immunotherapy regimen is usually FCR–a combination of Fludarabine, Cyclophosphamide and Rituximab. Almost all patients will go into remission after this treatment, and about 50 percent of those patients will go into complete remission. Since this treatment route is an aggressive one, and isn’t well tolerated in older patients, doctors typically will not recommend it for patients over age 65.
For older patients, doctors may use a different chemo-immunotherapy treatment called BR, says Dr. Davids, which is often a combination of Bendamustine and Rituximab. For patients who may even be older or too frail for BR, another treatment option is combining the oral chemo drug chlorambucil with the CD20 antibody obinutuzumab.
IGHV cells and CLL
A patient’s IGHV mutation status is a key factor in CLL prognosis. Doctors looking for a patient’s IGHV mutation status are looking at the age of the cell that allowed CLL to grow. If it is a younger, unmutated cell, it will likely be more aggressive. If it is an older, mutated cell, those tend to be slow-growing.
Dr. Matthew Davids, Associate Director of the CLL Center at Dana-Farber Cancer Institute, talks about the IGHV mutation and chronic lymphocytic leukemia
This information helps doctors determine which type of treatment to use. Typically, a patient with a mutated IGHV cell will go into remission for 10 to 15 years after initial treatment while a patient with an unmutated cell will typically only have 3 to 4 years of remission.
Dr. Davids told SurvivorNet in a prior interview that newer drugs like Ibrutinib, Idelalisib and Venetoclax tend to be more effective at treating un-mutated IGHV cells and offer some promise for the future.
Experts talk to Survivornet about the significant new advances in treating patients who have recently been diagnosed with later-stage CLL.