Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients.

Abstract

Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.

• Authors: Carlo Gambacorti Passerini, Francesca Farina, Alessandra Stasia, Sara Redaelli, Monica Ceccon, Luca Mologni, Cristina Messa, Luca Guerra, Giovanni Giudici, Elena Sala, Lara Mussolin, Dries Deeren, Michael H King, Michael Steurer, Rainer Ordemann, Amos M Cohen, Matthias Grube, Lea Bernard, Gianpaolo Chiriano, Laura Antolini, Rocco Piazza
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 106 Issue 2 Pg. djt378 (Feb 2014) ISSN: 1460-2105 [Electronic] United States
• PMID: 24491302 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Pyrazoles
• Pyridines
• Crizotinib
• p80(NPM-ALK) protein
• ALK protein, human
• Anaplastic Lymphoma Kinase
• Protein-Tyrosine Kinases
• Receptor Protein-Tyrosine Kinases

Topics

• Adult
• Anaplastic Lymphoma Kinase
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Crizotinib
• Disease-Free Survival
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Female
• Follow-Up Studies
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Kaplan-Meier Estimate
• Lymphoma, Non-Hodgkin (drug therapy, enzymology)
• Male
• Middle Aged
• Molecular Targeted Therapy (methods)
• Prospective Studies
• Protein Kinase Inhibitors (administration & dosage, therapeutic use)
• Protein-Tyrosine Kinases (analysis, drug effects)
• Pyrazoles (administration & dosage, therapeutic use)
• Pyridines (administration & dosage, therapeutic use)
• Receptor Protein-Tyrosine Kinases (analysis, drug effects)
• Recurrence
• Reverse Transcriptase Polymerase Chain Reaction
• Treatment Outcome