Pilot trial of ibrutinib in patients with relapsed or refractory T-cell lymphoma Journal Article
| Authors: | Kumar, A.; Vardhana, S.; Moskowitz, A. J.; Porcu, P.; Dogan, A.; Dubovsky, J. A.; Matasar, M. J.; Zhang, Z.; Younes, A.; Horwitz, S. M. |
| Article Title: | Pilot trial of ibrutinib in patients with relapsed or refractory T-cell lymphoma |
| Abstract: | Ibrutinib has previously been shown to inhibit Bruton's tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively. BTK inhibition with ibrutinib has demonstrated impressive clinical responses in a variety of B-cell malignancies. Whether ibrutinib inhibition of ITK can lead to clinical response in T-cell malignancies is unknown. We hypothesized that ibrutinib-mediated ITK inhibition in T-cell lymphoma would result in decreased signaling through the T-cell receptor pathway and promote antitumor immune response by driving selective cytotoxic Th1 CD4 effector T-cell differentiation. This pilot clinical trial evaluated 2 dose levels of ibrutinib: 560 and 840 mg orally daily. Fourteen patients with relapsed, refractory peripheral T-cell lymphoma and cutaneous T-cell lymphoma were enrolled. Both dose levels were safe and well tolerated, and no dose-limiting toxicities were observed. One patient achieved a partial response (overall response rate, 8% [1/13]). ITK occupancy studies demonstrated a mean occupancy of 50% (range, 15%-80%). Higher ITK occupancy of more than 50% correlated with higher serum levels of tumor necrosis factor-α and interferon-γ and favored a Th1 phenotype. Our data suggest that ibrutinib inhibition of ITK has limited clinical activity in T-cell lymphoma. This study is registered at www.clinicaltrials.gov as #NCT02309580. © 2018 by The American Society of Hematology. |
| Keywords: | adult; treatment outcome; aged; aged, 80 and over; middle aged; clinical trial; salvage therapy; protein kinase inhibitor; pyrimidines; protein kinase inhibitors; cutaneous t cell lymphoma; peripheral t cell lymphoma; t cell lymphoma; lymphoma, t-cell; pilot study; pilot projects; pyrazole derivative; pyrazoles; pyrimidine derivative; lymphoma, t-cell, peripheral; procedures; lymphoma, t-cell, cutaneous; ibrutinib; very elderly; humans; human; male; female |
| Journal Title: | Blood Advances |
| Volume: | 2 |
| Issue: | 8 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2018-04-24 |
| Start Page: | 871 |
| End Page: | 876 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2017011916 |
| PUBMED: | 29669753 |
| PROVIDER: | scopus |
| PMCID: | PMC5915998 |
| DOI/URL: | |
| Notes: | Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work