July 2015, Special ASCO Edition

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Ibrutinib Reduces Risk of Progression in Previously Treated CLL

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The combination of ibrutinib plus standard therapy with bendamustine/rituximab (IBR) significantly reduced the risk of progression or death by 80% compared with BR alone in previously treated patients with chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), according to results from HELIOS, one of the largest phase 3 trials in this setting.

“There are countless patients with CLL for whom this drug is a blessing. Ibrutinib reduced the risk of progression or death by 80%. This an impactful therapy that changes the course of disease early on,” said lead author Asher A. Chanan-Khan, MD, Mayo Clinic, Jacksonville, FL.

HELIOS is the first placebo-controlled study of ibrutinib in CLL/SLL and the first large phase 3 trial to evaluate a novel targeted drug with chemoimmunotherapy.

The randomized, double-blind, placebo-controlled, international phase 3 HELIOS trial randomized 578 patients with previously treated CLL/SLL to receive IBR followed by ibrutinib maintenance or placebo plus standard therapy followed by placebo maintenance. Treatment was for a maximum of 6 cycles, and maintenance therapy was continued until progression or unacceptable toxicity. Crossover to ibrutinib maintenance was allowed for patients with progressive disease in the placebo maintenance arm.

Patients with del17p were excluded.

At baseline, 26% were purine analog refractory. About 49% had received 1 prior line of therapy; about 25%, 2 prior lines; and about 26%, 3 or more prior lines of therapy.

The primary end point was progression-free survival (PFS) as assessed by an independent review committee. At 17.2 months of follow-up, median PFS had not been reached in the IBR arm versus 13.3 months with standard therapy (P <.0001). IBR significantly reduced the risk of progression or death by 80% compared with placebo plus BR.

Ibrutinib was favored in all subgroups analyzed, including age, sex, diagnosis, Rai stage at screening, prior lines of therapy, bulky disease, baseline Eastern Cooperative Oncology Group status, and presence or absence of del11q and IgVH.

At a median follow-up of 17.2 months, overall survival had not been reached in either arm. Ibrutinib reduced the risk of death by 37% (P = .05598). Chanan- Khan noted that survival results are confounded by crossover to single-agent ibrutinib for maintenance by 90 patients (31%) in the placebo arm.

The overall response rate was significantly higher with IBR versus placebo plus BR: 82.7% versus 67.8%.

No unexpected side effects were reported. The safety profiles were consistent for each of the drugs. The most frequent side effects were low blood cell counts, nausea, and diarrhea.

“These results represent a changing point in the treatment of CLL. The standard of care should now be ibrutinib plus BR for previously treated patients,” Chanan-Khan stated.

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