The U.S. Food and Drug Administration (FDA) granted accelerated approval to ibrutinib for marginal zone lymphoma (MZL) following at least one prior anti-CD20-based therapy.
The decision was based on the results of the pivotal, open-label PCYC-1121 study presented at the 2016 ASH Annual Meeting that found that ibrutinib resulted in an objective response rate of 46 percent, including a complete response rate of 3.2 percent.
A total of 63 patients (median age = 66 years; range = 30-92 years) with relapsed/refractory MZL (including splenic [n=14], nodal [n=17], and extranodal [n=32]) received ibrutinib 560 mg orally once daily. Previous therapies included:
- splenectomy (6%)
- radiotherapy (14%)
- rituximab monotherapy (27%)
- CD20 antibody-containing chemoimmunotherapy (64%)
After a median follow-up of 19.4 months, the median duration of response and median overall survival were not reached. The median time to initial response was 4.5 months (range = 2.3-16.4 months), and the median progression-free survival was 14.2 months (range = 8.3 months to not reached).
The most common adverse events (AEs) included thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema (24%), arthralgia (24%), neutropenia (22%), cough (22%), dyspnea (21%), and upper respiratory tract infection (21%). The most common grade 3/4 AEs were increased hemoglobin (13%), decreased neutrophils (13%), and pneumonia (10%). Serious AEs occurred in 28 patients (44%), with grade 3/4 pneumonia being the most common (n=5; 8%).
Three treatment-related AEs resulted in death, and 38 patients (60%) discontinued treatment because of progressive disease (30%), AEs (19%), patient decision (5%), or physician decision (6%). The most common AE leading to treatment discontinuation was diarrhea (n=2; 3%).
The FDA had previously approved ibrutinib for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma, and Waldenström macroglobulinemia.
Sources: AbbVie news release, January 19, 2017; Noy A, de Vos S, Thieblemont C, et al. Single-agent ibrutinib demonstrates efficacy and safety in patients with relapsed/refractory marginal zone lymphoma: a multicenter, open-label, phase 2 study. Abstract #1213. Presented at the 2016 ASH Annual Meeting, December 5, 2016; San Diego, California.