The U.S. Food and Drug Administration (FDA) approved the targeted therapy ibrutinib for treating patients with mantle cell lymphoma who have received at least one prior therapy. The drug is the second designated by the FDA as a “breakthrough therapy” to be granted approval by the agency.

The U.S. Food and Drug Administration (FDA) has approved the targeted therapy ibrutinib (Imbruvica; Johnson & Johnson and Pharmacyclics) for treating patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

MCL accounts for about 7% of all cases of non-Hodgkin lymphoma in the United States. It is most often diagnosed in older males (median age 68) and generally carries a poor long-term prognosis.

The FDA approved ibrutinib, an oral inhibitor of Bruton's tyrosine kinase, based on results from a single-arm, international phase II clinical trial published in the New England Journal of Medicine. Among 111 patients with relapsed or refractory MCL, 21% demonstrated a complete response and 47% had a partial response. The median response duration was about 17.5 months, which the authors described as durable single-agent activity in this population. The trial showed a low occurrence of grade 3 and 4 toxicity events.

“It was recognized early on as a drug that would be very successful in treating lymphoma patients,” says Julie Vose, MD, chief of hematology and oncology at the University of Nebraska Medical Center in Omaha. “It's very promising, and I've had many patients that it has helped.”

However, she notes that the estimated annual cost of the oral drug is $130,000, and the steep price tag will cause severe difficulties for many patients.

Ibrutinib is the third treatment approved for MCL. It joins the thalidomide analog lenalidomide (Revlimid; Celgene), which was approved in June 2013 for patients who have relapsed or progressed after two prior therapies, and the proteasome inhibitor bortezomib (Velcade; Takeda Pharmaceutical), which was approved in 2006 for patients who have received at least one prior therapy.

Younger patients with the disease are frequently treated initially with an aggressive chemotherapy regimen with rituximab (Rituxan; Genentech), followed by a stem cell transplant. Older patients may receive a lower-intensity chemotherapy regimen followed by rituximab as maintenance therapy.

Vose notes that in the clinical trial, ibrutinib's overall response rate was significantly higher than those shown by lenalidomide or bortezomib in the clinical trials that led to their approvals. Though ibrutinib did cause some side effects, they were rarely severe.

Bijal Shah, MD, a medical oncologist at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, FL, characterizes ibrutinib as a critical step forward in the design of treatments that couple low toxicity with the efficacy of chemotherapy. “I think we're finally in a place where we can start to talk about a non-chemotherapy-based approach to obtaining, and ultimately maintaining, remission,” he says.

Ibrutinib is the second drug designated by the FDA as a “breakthrough therapy” to be granted approval. The breakthrough therapy designation hastens the clinical development and review of a therapy for which early clinical evidence suggests an improvement over existing treatments on at least one significant endpoint.

In June, its manufacturers submitted the drug for approval to treat patients with chronic lymphocytic leukemia (CLL) as well as MCL. The FDA has not publicly released any information on potential approval for CLL.

©2013 American Association for Cancer Research.
2013