Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma

Blood. 2017 Apr 20;129(16):2224-2232. doi: 10.1182/blood-2016-10-747345. Epub 2017 Feb 6.

Abstract

Marginal zone lymphoma (MZL) is a heterogeneous B-cell malignancy for which no standard treatment exists. MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation. We conducted a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of ibrutinib in previously treated MZL. Patients with histologically confirmed MZL of all subtypes who received ≥1 prior therapy with an anti-CD20 antibody-containing regimen were treated with 560 mg ibrutinib orally once daily until progression or unacceptable toxicity. The primary end point was independent review committee-assessed overall response rate (ORR) by 2007 International Working Group criteria. Among 63 enrolled patients, median age was 66 years (range, 30-92). Median number of prior systemic therapies was 2 (range, 1-9), and 63% received ≥1 prior chemoimmunotherapy. In 60 evaluable patients, ORR was 48% (95% confidence interval [CI], 35-62). With median follow-up of 19.4 months, median duration of response was not reached (95% CI, 16.7 to not estimable), and median progression-free survival was 14.2 months (95% CI, 8.3 to not estimable). Grade ≥3 adverse events (AEs; >5%) included anemia, pneumonia, and fatigue. Serious AEs of any grade occurred in 44%, with grade 3-4 pneumonia being the most common (8%). Rates of discontinuation and dose reductions due to AEs were 17% and 10%, respectively. Single-agent ibrutinib induced durable responses with a favorable benefit-risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy. As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL. This study is registered at www.clinicaltrials.gov as #NCT01980628.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Agammaglobulinaemia Tyrosine Kinase
  • Aged
  • Aged, 80 and over
  • Anemia / chemically induced
  • Anemia / pathology
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Disease-Free Survival
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Fatigue / pathology
  • Female
  • Humans
  • Immunotherapy / methods
  • Lymphoma, B-Cell, Marginal Zone / immunology
  • Lymphoma, B-Cell, Marginal Zone / mortality
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphoma, B-Cell, Marginal Zone / therapy*
  • Male
  • Middle Aged
  • Pneumonia / chemically induced
  • Pneumonia / pathology
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Recurrence

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase

Associated data

  • ClinicalTrials.gov/NCT01980628
  • ClinicalTrials.gov/NCT01980628