Investigational Drug Shows Benefit in CLL

In an early-phase study, PCI-32765, a BTK inhibitor, was shown to work against CLL, a type of non-Hodgkin lymphoma.

Patients with chronic lymphocytic leukemia (CLL) often can live for years symptom-free. When symptoms, which can include enlarged lymph nodes and frequent infections, do appear many patients receive chemotherapy.

Researchers are testing a new targeted therapy that blocks a B-cell signaling pathway, specifically the Bruton’s tyrosine kinase (BTK), which is responsible for normal B-cell development. When that signaling goes awry, such as BTK getting stuck in the “on” position, non-Hodgkin lymphoma cells can develop and multiply.

In an early-phase study, PCI-32765, a BTK inhibitor, was shown to work against CLL, a type of non-Hodgkin lymphoma. A small group of patients who had relapsed CLL and no longer responded to standard therapy were given PCI-32765 at varying doses.

At 10 months, 70 percent of patients at the lower dose had a response to therapy, including some patients who had a reduction in lymph node size. To date, only 8 percent of patients on PCI-32765 have reported disease progression. Taking into account that nearly three-quarters of patients in the trial had at least one high-risk factor for treatment-resistant CLL, researchers are optimistic. In addition, these numbers are an improvement over the preliminary results announced last year.

Side effects of PCI-32765 included diarrhea, fatigue and nausea, but Susan O’Brien, MD, of M.D. Anderson Cancer Center in Houston, noted that myelosuppression (impaired bone marrow function), a common treatment side effect in CLL that can increase the risk of infection, was not seen with the drug.

“The efficacy is increasing over time; there is a relative lack of toxicity and lack of myelosuppression,” she said during a press briefing of the study results. “These agents will really change the paradigm for treatment of CLL.”

The drug is also showing activity against mantle cell lymphoma (MCL), a less common type of non-Hodgkin lymphoma that is particularly hard to treat. A phase 2 study found that after about four months more than two-thirds of patients with MCL responded to the drug, regardless if they had been treated with Velcade (bortezomib), a targeted therapy commonly used for the disease. Researchers are hopeful the drug will continue to be studied in a phase 3 trial for patients with MCL.