First Drug Approved for Marginal Zone Lymphoma

Zosia Chustecka


January 19, 2017

The novel agent ibrutinib (Imbruvica, Janssen/Pharmacyclics) has been approved in the United States for the additional indication of marginal zone lymphoma (MZL), making it the first therapy to be specifically approved for use in this condition.

This indication is the fifth for ibrutinib, which is already approved for use in chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström's macroglobulinemia, and mantle cell lymphoma.

The drug has a novel mechanism of action, acting as an inhibitor of Bruton’s tyrosine kinase.

MZL develops at the margins, or edges, of lymph nodes and various tissues, and it accounts for about 12% of all cases of non-Hodgkin’s lymphoma in adults.

The new approval is for use in relapsed/refractory cases of MZL in patients who have already received at least one prior anti-CD20–based therapy.

This is an accelerated approval and is based on overall response rate (ORR), so further data on clinical benefit are awaited from a confirmatory trial. 

The data to support the approval come from a multicenter, open-label single arm of the phase 2 trial known as PCYC-1121, which involved 63 patients with MZL who received at least one prior therapy. All three subtypes of the disease were included: mucosa-associated lymphoid tissue (MALT; n = 32), nodal MZL (n = 17), and splenic MZL (n = 14).

Ibrutinib demonstrated a 46% ORR, with 3.2% of patients achieving complete responses and 42.9% achieving partial responses.  Efficacy was observed across all three MZL subtypes (with ORRs 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 - not reached), with median follow-up of 19.4 months. The median time to initial response was 4.5 months (range, 2.3 - 16.4).

These data were presented at the 58th Annual American Society of Hematology (ASH) Meeting in December 2016, the manufacturers note.

The most common adverse events 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%), and dyspnea and upper respiratory tract infection (21% each).

The most common grade 3 or 4 adverse events were decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%). Warnings and precautions for ibrutinib include hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity, the manufacturers note.

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