FDA Approves IMBRUVICA® as First Treatment Specifically Indicated for Relapsed/Refractory Marginal Z

AbbVie has announced that the U.S. Food and Drug Administration (FDA) approved IMBRUVICA® (ibrutinib) for the treatment of patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.1 This indication is approved under accelerated approval based on overall response rate (ORR), and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

"The FDA approval of IMBRUVICA for relapsed/refractory marginal zone lymphoma is significant, and we are proud of the culmination of this extensive clinical research program, representing the first approved treatment specifically for patients with this rare type of non-Hodgkin's lymphoma," said Darrin Beaupre, M.D., Ph.D., Head of Early Development and Immunotherapy at Pharmacyclics LLC, an AbbVie company. "This milestone marks the fifth patient population for whom IMBRUVICA is now approved and broadens the number of patients who may be treated with the medication. We continue to research IMBRUVICA across many disease areas, including but not limited to other B-cell malignancies."

The approval in MZL is based on data from the Phase 2, open-label, multi-center, single-arm PCYC-1121 study, which evaluated the safety and efficacy of IMBRUVICA in MZL patients who require systemic therapy and have received at least one prior anti-CD20-based therapy. The efficacy analysis included 63 patients with three sub-types of MZL: mucosa-associated lymphoid tissue (MALT; N=32), nodal (N=17) and splenic (N=14). The ORR was achieved in nearly half (46%) of the patients (95% CI: 33.4-59.1) as assessed by an Independent Review Committee (IRC) using criteria adopted from the International Working Group criteria for malignant lymphoma, with efficacy observed across all three MZL sub-types. The median time to response was 4.5 months (range, 2.3-16.4 months).  In the trial, 3.2% of patients had a complete response (CR) and 42.9% of patients had a partial response (PR). The median duration of responses was not reached (NR) (range 16.7 months to NR).1The data were previously presented at the American Society of Hematology (ASH) Annual Meeting (December 2016). 

"In the Phase 2 trial, IMBRUVICA demonstrated impressive response rates and duration of response in relapsed/refractory marginal zone lymphoma patients," said Ariela Noy, M.D., Hematologic Oncologist at Memorial Sloan Kettering Cancer Center in New York and lead investigator of the study.* "The hematology-oncology community welcomes a new option like IMBRUVICA, which helps fill a significant treatment gap for previously treated MZL patients who are in need of non-chemotherapy options."

Overall, the safety data from this study was consistent with the known safety profile of IMBRUVICA in B-cell malignancies. The most common adverse events (AEs) of all Grades (occurring in ≥20% of MZL patients treated with IMBRUVICA) included thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema and arthralgia (24% each), neutropenia and cough (22% each), and dyspnea and upper respiratory tract infection (21% each). The most common (>10%) Grade 3 or 4 AEs were decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%).1

The risks associated with IMBRUVICA as listed in the Warnings and Precautions section of the prescribing information are hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, secondary primary malignancies, tumor lysis syndrome and embryo fetal toxicities.

IMBRUVICA is now approved to treat patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy, as well as patients with other non-Hodgkin's lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including patients with 17p deletion; patients with mantle cell lymphoma (MCL) who have received at least one prior therapy; and patients with Waldenström's macroglobulinemia (WM).1 Continued approval for the MZL and MCL indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.