Roxanne Nelson

May 16, 2013

A new targeted agent produced rapid and long-lasting tumor shrinkage in half of patients with relapsed or treatment-resistant chronic lymphocytic leukemia (CLL) in a phase 1 study.

Treatment with idelalisib (GS-1101, Gilead) delayed disease progression by an average 17 months in heavily pretreated patients with relapsed/refractory CLL. This is longer than what is typically expected for a sixth-line therapy, which might show a benefit of 6 to 12 months, the authors note.

Idelalisib is a first-in-class selective oral inhibitor of PI3K-δ that targets malignant B-cells. Although there have been previous studies of PI3K inhibitors, this is the first specifically looking at patients with CLL.

"Relapsed and refractory CLL has few effective treatment options," said lead study author Jennifer Brown, MD, PhD, assistant professor of medicine at Dana-Farber Cancer Institute in Boston, Massachusetts. She presented study highlights during a presscast held in advance of the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

The data from this early study show that idelalisib rapidly induces durable responses in heavily pretreated patients, explained Dr. Brown. The safety profile of idelalisib is favorable, and "its substantial clinical activity in CLL justifies further development."

Alternative to Chemo?

"I think this is another exciting story of early success in precision medicine," said ASCO president Sandra M. Swain, MD, who served as a commenter in the presscast.

She noted that there was an overall response rate of 56%, but "even more striking was the progression-free survival of 17 months, which is pretty incredible." In addition, 2 patients achieved full remission.

On the basis of forthcoming results from phase III trials, "we may soon have an alternative to chemotherapy for slow-growing blood cancers," Dr. Swain said.

Study Details

In their study, Dr. Brown and colleagues evaluated idelalisib in 54 refractory and high-risk patients with CLL. The median age was 63 years, and 80% of the patients had bulky lymphadenopathy, 70% had refractory disease, 91% had unmutated IGHV, 24% had del17p and/or a TP53 mutation, 28% had del11q, and 17% had a NOTCH1 mutation. Patients had received a median of 5 previous therapies (range, 2 - 14).

Study participants received continuous single-agent oral idelalisib in doses ranging from 50 to 350 mg once or twice a day. The therapy continued in an extension study for as long as the patient continued to benefit from it. Median exposure was 9 months, 25 (46%) patients completed the primary study, and 23 (43%) enrolled in the extension study.

Thirty patients (56%) responded to therapy — 2 achieved a complete response and 28 achieved a partial response. In addition, 21 (39%) had stable disease.

"Idelalisib also rapidly induced deep and durable lymph node responses," said Dr. Brown. Forty-four patients (81%) showed a lymph node response.

Median time to first response was 1.9 months, median progression-free survival was 17.0 months, and median duration of response was 18.0 months.

Treatment with idelalisib resulted in the resolution of splenomegaly in 14 of 20 patients (70%) and the normalization of cytopenia in 17 of 25 (68%) patients with anemia, 27 of 34 (79%) with thrombocytopenia, and 15 of 15 (100%) with neutropenia.

Adverse events were manageable, and only 7% of patients stopped treatment because of adverse effects related to the agent.

Table. Commonly Report Adverse Events Related to Idelalisib

Adverse Event Any Grade, % Grade 3 or Higher, %
Fatigue 31 2
Diarrhea 30 6
Pyrexia 30 4
Rash 22 0
Upper respiratory tract infection 22 0
Pneumonia 20 19


Phase 3 trials of idelalisib in combination with rituximab or bendamustine/rituximab are currently ongoing.

This research was supported by Gilead Sciences. Coauthor Ian Flinn, MD, PhD, reports receiving research funding from Gilead Sciences.

2013 Annual Meeting of the American Society of Clinical Oncology. Abstract 7003. To be presented June 4, 2013.


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