- Idelalisib is a drug that targets a protein found only on certain types of blood cells.
- The drug is already approved to treat CLL patients who cannot tolerate chemotherapy due to other health conditions.
- Patients who got the drug in addition to standard treatment were found to have improved survival compared with those who got standard treatment alone.
- The investigators say these findings will change the standard of care for people with CLL.
As researchers develop a greater number of targeted therapies for cancer, they’re also increasingly studying new treatment combinations. These combinations may better control the disease by targeting multiple aspects of the cancer without burdening patients with too many toxic side effects.
New findings from an international study led by a Memorial Sloan Kettering investigator show that adding a targeted drug called idelalisib (Zydelig®) to standard treatment can greatly improve outcomes for patients with chronic lymphocytic leukemia (CLL) that has relapsed or stopped responding to other treatments. CLL is one of the most common types of leukemia found in adults.
In patients receiving idelalisib, the disease was halted for approximately twice as long before progressing again compared with patients who received a placebo. The results of the placebo-controlled trial were so encouraging that the trial was ended early so that all patients currently receiving the placebo could receive the experimental treatment.
“We believe that based on the improved outcomes we saw in this study, idelalisib and other drugs that act in a similar manner should be added to the standard of care,” says MSK medical oncologist Andrew Zelenetz, lead author of the multicenter study, which was presented this week at the American Society of Hematology annual meeting in Orlando.
Targeting White Blood Cells
CLL is a disease in which the bone marrow makes too many of a type of white blood cell called a lymphocyte. It can’t be cured, but most people can live with the illness for many years. CLL is often detected incidentally during blood tests for another condition. In the early stages, people with CLL are only monitored and observed.
After the appearance of symptoms, which can include pain and excessive bleeding, treatment generally begins with chemotherapy. After that, patients usually go into remission several times, with the remission duration shrinking as the disease advances.
Idelalisib is a highly selective drug that affects certain blood cells. Specifically, it inhibits one form of a protein called PI3 kinase, which is present only in white blood cells and is critical for their survival. Idelalisib received FDA approval last year for the treatment of CLL patients whose disease has relapsed but who cannot tolerate chemotherapy due to other medical conditions. It is also approved to treat certain types of lymphoma.
In the phase III trial, the patients received the standard treatment with either idelalisib or a placebo added. The standard regimen, known as BR treatment, is the chemotherapy drug bendamustine combined with rituximab, a monoclonal antibody that targets a protein found on the surface of immune cells called B cells.Back to top
Slowing the Disease Progression
In the study, 407 patients had idelalisib added to their BR treatment, while 409 patients received a placebo in addition to BR treatment. About two-thirds of the patients had relapsed after earlier treatment; one-third had cancer that was refractory, meaning that it had stopped responding to other therapies. Many of the patients had significant mutations in their tumor cells, indicating that they had a particularly difficult-to-treat disease.
The average time that it took for the patients’ disease to progress was 23 months for those receiving idelalisib — more than double the 11 months for patients receiving the placebo. An equal benefit was seen in patients with relapsed and refractory disease. The treatment did have side effects, including fever, diarrhea, and pneumonia, but they were not unexpected based on earlier studies of idelalisib.
“In addition to delaying the time to progression, overall survival was significantly improved by the addition of idelalisib to a standard of care, which reduced the risk of death by 45 percent,” says Dr. Zelenetz, who is also Vice Chair of Medical Informatics in the Department of Medicine.Back to top
Cancer as a Chronic Disease
He notes that although survival is improved with idelalisib, the drug is not a cure. “People will still progress with this drug, but it will be slower and they will live longer,” he says.
Dr. Zelenetz expects that adding idelalisib to standard treatment for several types of slow-growing B cell lymphoma, including follicular lymphoma and Waldenstrom macroglobulinemia, will result in a similar benefit to what’s been seen in patients with CLL. But he explains that idelalisib is not likely to be effective against solid tumors that have other forms of the mutated PI3 kinase protein because it targets a version that’s found only in white blood cells.
Over the past decade, advances in the treatment of many types of cancer have resulted in therapies that — while not curative — can greatly extend patients’ lives. When given in a sequential manner, these treatments can add years to people’s life expectancy.Back to top