Treatment advances for relapsed or refractory chronic lymphocytic leukemia

This paper reviewed advances in treatment options for relapsed and refractory chronic lymphocytic leukemia. 

Chronic lymphocytic leukemia (CLL) is a cancer of the blood and blood forming cells. Despite a good response to initial therapy, most patients relapse and require further treatment. Some patients may stop responding to treatment (known as refractory disease). Current therapies include chemotherapy combinations and stem cell treatment. New treatments, however, are under investigation.

The current study reviewed new treatments under investigation for relapsed or refractory CLL.

Ibrutinib is a treatment that blocks a protein signaling pathway that leads to cancer growth. Initial studies found that 71% of patients responded to ibrutinib. Ibrutinib received FDA-approval in 2014 for relapsed CLL.  Another trial compared ibrutinib to ofatumumab (Arzerra) in patients with relapsed or refractory CLL.  90% of patients treated with ibrutinib  were alive after 12 months compared to 81% of patients treated with ofatumumab. With regards to safety of ibrutinib, diarrhea was seen in 5% of patients. 3% of patients had atrial fibrillation (abnormal heart rhythm). Minor bleeds under the skin were seen in 44% of patients while major bleeding occurred in 0.5% of patients.

Idelalisib is a drug that was approved in 2014 for the treatment of relapsed CLL in combination with rituximab. A phase 3 trial compared idelalisib plus rituximab to rituximab alone. At 24 weeks, 93% of patients receiving idelalisib and rituximab had no worsening disease compared to 46% receiving rituximab alone. With regards to safety, diarrhea was seen in 21% of patients. A low white blood cell count was seen in 60% of patients. Bleeding was seen in 14% of patients. Pneumonitis, an inflammation of lung tissue, was seen in 6% of patients. It is recommended that measures be taken to prevent pneumonitis before starting treatment with idelalisib. 

Venetoclax was recently approved for the treatment of previously treated CLL with the 17p deletion genetic mutation (permanent change). In an early phase 1 trial, 84% of patients responded to venetoclax. A phase 2 study looked at venetoclax alone in relapsed or refractory CLL with 17p deletion genetic mutation. After an average follow-up of 12.1 months, 79% of patients responded to treatment.  Serious side effects including fever and low blood count occurred in 55% of patients. 

This trial reviewed the newer treatments, ibrutinib, idelalisib, and venetoclax, that have been approved for treatment of relapsed and refractory CLL. 

Talk to your doctor about new therapies to treat relapsed and refractory CLL.