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.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Anaplastic Lymphoma Kinase
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Crizotinib
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Disease-Free Survival
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Drug Administration Schedule
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Drug Resistance, Neoplasm
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Female
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Follow-Up Studies
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Humans
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Immunohistochemistry
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In Situ Hybridization, Fluorescence
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Kaplan-Meier Estimate
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Lymphoma, Non-Hodgkin / drug therapy*
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Lymphoma, Non-Hodgkin / enzymology
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Male
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Middle Aged
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Molecular Targeted Therapy / methods*
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Prospective Studies
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / therapeutic use*
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Protein-Tyrosine Kinases / analysis*
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Protein-Tyrosine Kinases / drug effects
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Pyrazoles / administration & dosage
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Pyrazoles / therapeutic use*
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Pyridines / administration & dosage
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Pyridines / therapeutic use*
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Receptor Protein-Tyrosine Kinases / analysis*
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Receptor Protein-Tyrosine Kinases / drug effects
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Recurrence
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Reverse Transcriptase Polymerase Chain Reaction
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Treatment Outcome
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Pyrazoles
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Pyridines
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Crizotinib
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p80(NPM-ALK) protein
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ALK protein, human
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Anaplastic Lymphoma Kinase
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Protein-Tyrosine Kinases
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Receptor Protein-Tyrosine Kinases