Single-Agent Ibrutinib Leads to Durable Responses in CLL

In both treatment-naïve and relapsed/refractory patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL), single-agent ibrutinib led to durable responses, according to research presented by Steven Coutre, MD, a professor of medicine in hematology at the Stanford University Medical Center, at this year’s AACR.

Dr. Coutre and colleagues presented long-term data from a phase I/IIb study of ibrutinib in 94 patients: 27 treatment-naïve and 67 relapsed/refractory. Notably, patients in the relapsed/refractory group had been treated with a median of four prior therapies.

Ibrutinib is a first-in-class, once-daily oral Bruton’s tyrosine kinase inhibitor. The drug is currently approved by the U.S. FDA for the treatment of CLL in patients who have received at least one prior therapy and for all CLL patients who have del 17p, as well as for patients with Waldenström’s macroglobulinemia. Ibrutinib also received accelerated approval for the treatment of mantle cell lymphoma in patients who failed at least one prior therapy.

Approximately 115,000 U.S. patients are living with CLL and SLL, and nearly 16,000 patients are newly diagnosed each year. As these conditions are generally thought to be incurable, identifying new treatments is particularly important.

After 45-months of follow-up, 91 percent of all patients who received single-agent ibrutinib (420 mg) achieved an overall response, with 14 percent achieving a complete response. As seen in the TABLE, rates of complete response were higher in the treatment-naïve group than in the relapsed/refractory group. Investigators presented the results of the phase 1/2b trial, though the study is ongoing. While the median response duration and progression-free survival (PFS) had not yet been reached at the time of reporting these findings, in a landmark analysis, 30-month PFS and overall survival rates were high in both cohorts – indicating long-lasting responses with single-agent ibrutinib.

During follow-up, only one patient with previously untreated CLL experienced disease progression.

The most commonly reported grade ≥3 adverse events included hypertension (23%), pneumonia (15%), neutropenia (13%), atrial fibrillation (7%), and diarrhea (7%). At the time of analysis, 22 (81%) treatment-naïve and 40 (60%) relapsed/refractory patients continued on ibrutinib, with 22 (81%) and 28 (42%), respectively, remaining on treatment for more than two years.


Coutre S, Furman R, Flinn I, et al. Long-term treatment with single-agent ibrutinib 420 mg leads to durable responses including complete responses in CLL. Abstract #CT132. Presented at the American Association for Cancer Research Annual Meeting, April 19, 2015.

TABLE. Efficacy of Single-Agent Ibrutinib
Efficacy Parameter Treatment-Naïve
Overall response rate 23 (85%) 63 (94%)
Complete response 7 (26%) 6 (9%)
Partial response/Partial response-lymphocytosis 16 (59%) 57 (85%)
Duration of response (months) Not reached Not reached
30-month PFS (95% Cl) 96% (74, 99) 76% (63, 85)
30-month OS rate (95% Cl) 96% (78, 99) 87% (76, 93)