FDA approves ibrutinib for previously treated MCL


Micrograph showing MCL

The US Food and Drug Administration (FDA) has has granted accelerated approval for

ibrutinib (Imbruvica) to treat patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

Ibrutinib works by inhibiting the function of Bruton’s tyrosine kinase, a molecule that plays an important role in the survival of malignant B cells.

The drug showed promising results in the phase 2 PCYC-1104 trial, which was presented at ASH 2012 and published in NEJM in August.

The FDA granted ibrutinib breakthrough therapy designation because of these results and the life-threatening nature of MCL. Ibrutinib is the second drug with breakthrough therapy designation to receive FDA approval.

The FDA granted ibrutinib accelerated approval, rather than traditional approval, because the drug has not yet shown a clinical benefit. Accelerated approval of a drug is based

on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to

predict clinical benefit.

PCYC-1104 trial

The data published in NEJM included 111 patients who received ibrutinib at 560 mg daily in continuous, 28-day cycles until disease progression.


overall response rate was 68%, with a complete response rate of 21% and

a partial response rate of 47%. With an estimated median follow-up of

15.3 months, the estimated median response duration was 17.5 months.


estimated progression-free survival was 13.9 months, and the overall

survival was not reached. The estimated rate of overall survival was 58%

at 18 months.

Common nonhematologic adverse events included

diarrhea (50%), fatigue (41%), nausea (31%), peripheral edema (28%),

dyspnea (27%), constipation (25%), upper respiratory tract infection

(23%), vomiting (23%), and decreased appetite (21%). The most common

grade 3, 4, or 5 infection was pneumonia (6%).

Grade 3 and 4

hematologic adverse events included neutropenia (16%), thrombocytopenia

(11%), and anemia (10%). Grade 3 bleeding events occurred in 5 patients.

The “Warnings and Precautions” section of ibrutinib’s prescribing information notes that patients taking ibrutinib have experienced hemorrhage, fatal and non-fatal infections, myelosuppression, renal toxicity, second primary malignancies, and embryo-fetal toxicity.

For the full prescribing information, visit

Ibrutinib is now commercially available. It is co-marketed by Pharmacyclics (based in Sunnyvale, California) and Janssen Biotech, Inc. (based in Raritan, New Jersey).

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