Ibrutinib received approval by the FDA for the treatment of patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for this indication based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
"Patients with relapsed/refractory marginal zone lymphoma are in critical need of treatment options to manage living with this rare, serious blood cancer," said Ariela Noy, MD, Hematologic Oncologist at Memorial Sloan Kettering Cancer Center in New York and lead investigator of the study. "This approval of ibrutinib represents a welcome new oral option for the MZL community and is the first approved therapy for these patients."
The approval is based on results from the multi-center, open-label single arm, phase II PCYC-1121 trial assessing the safety and efficacy of ibrutinib in 63 patients with MZL who received at least one prior therapy, including all three subtypes: mucosa-associated lymphoid tissue (MALT; n=32), nodal MZL (NMZL; n=17), and splenic MZL (SMZL; n=14).
The responses were assessed by an Independent Review Committee using criteria adopted from the International Working Group criteria for malignant lymphoma and demonstrated a 46 percent ORR (95% CI: 33.4-59.1), with 3.2 percent of patients achieving complete responses and 42.9 percent achieving partial responses.
Efficacy was observed across all three MZL subtypes (ORR of 46.9%, 41.2%, and 50.0% for MALT, nodal, and splenic subtypes, respectively). The median duration of response was not reached (range, 16.7-NR), with median follow-up of 19.4 months. The median time to initial response was 4.5 months (range, 2.3-16.4). The data were presented at the American Society of Hematology Annual Meeting in December 2016 (Abstract1213).
Warnings and precautions for ibrutinib include hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity. The most common (>20%) adverse events (AEs) of all grades 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 (22%), cough (22%), 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%).