FDA Grants Imbruvica an Accelerated Approval for Marginal Zone Lymphoma

The US Food and Drug Administration (FDA) granted Imbruvica (ibrutinib) an accelerated approval for patients with marginal zone lymphoma (MZL) who require systemic therapy following at least one prior anti-CD20-based therapy, based on the findings from a single-arm phase 2 study.

In the pivotal open-label study, the objective response rates (ORR) with Imbruvica was 46 percent, with a complete response rate of 3.2 percent, according to findings presented at the 2016 American Society of Hematology (ASH) Annual Meeting. The median progression-free survival was 14.2 months with Imbruvica and the median overall survival was not yet reached at a median follow-up of 19.4 months.

"Patients with relapsed/refractory marginal zone lymphoma are in critical need of treatment options to manage living with this rare, serious blood cancer," lead investigator Ariela Noy, M.D., Hematologic Oncologist at Memorial Sloan Kettering Cancer Center, said in a statement. "This approval of Imbruvica represents a welcome new oral option for the MZL community and is the first approved therapy for these patients."

In the trial, which was known as PCYC-1121, 63 patients with relapsed or refractory MZL received Imbruvica at 560 mg orally once daily. The trial included patients with splenic (14 patients), nodal (17 patients) or extranodal MZL (32 patients) who had received one or more prior therapies, including an anti-CD20 antibody. All patients had an ECOG performance status of less than 2 and 33 percent had bone marrow involvement. All patients had an estimated life expectancy of more than three months.

Overall, six percent of patients had undergone a prior splenectomy and 14 percent had received prior radiotherapy. Prior to entering the trial, Rituxan (rituximab) monotherapy was received by 27 percent of patients and a CD20 antibody-containing chemoimmunotherapy regimen was received by 64 percent of participants.

In those with extranodal or mucosa-associated lymphoid tissue disease, the ORR was 46.9 percent. In the nodal group, the ORR was 41.2 percent and in the splenic arm the ORR was 50 percent. After a median follow-up of 19.4 months, the median duration of response was not reached (range, 16.7-NR). The median time to initial response was 4.5 months (range, 2.3-16.4).

“The responses and clinical benefit seen with single-agent ibrutinib in patients with marginal zone lymphoma who have already failed at least one other therapy are very encouraging,” Noy said, during the ASH meeting. “It is important for these patients to have treatment options.”

The most common adverse events (AEs) of all grades included thrombocytopenia (49 percent), fatigue (44 percent), anemia (43 percent), diarrhea (43 percent), bruising (41 percent), musculoskeletal pain (40 percent), hemorrhage (30 percent), rash (29 percent), nausea (25 percent), peripheral edema (24 percent), arthralgia (24 percent), neutropenia (22 percent), cough (22 percent), dyspnea (21 percent) and upper respiratory tract infection (21 percent). The most common grade 3/4 AEs were decreases in hemoglobin (13 percent), neutrophil decrease (13 percent) and pneumonia (10 percent).

"This approval broadens the indication for Imbruvica to include relapsed/refractory marginal zone lymphoma. It addresses a great unmet need for patients living with this serious blood cancer," said Peter F. Lebowitz, M.D., Ph.D., global oncology head, Janssen Biotech, which is the company jointly developing and commercializing the agent along with the AbbVie company Pharmacyclics.

"Building on our longstanding commitment of providing meaningful treatment solutions for people living with hematological malignancies, this milestone marks the fifth blood cancer indication for this medication," said Lebowitz. "We continue to research its potential across a range of B-cell malignancies based on the drug's mechanism of action."

The accelerated approval for MZL is contingent upon findings from a larger confirmatory study. Imbruvica has previously been approved by the FDA for the treatment of patients with mantle cell lymphoma, chronic lymphocytic leukemia and small lymphocytic lymphoma, and Waldenström’s macroglobulinemia.