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

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 AntoliniRocco Piazza

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalJournal of the National Cancer Institute
Volume106
Issue number2
DOIs
StatePublished - Feb 2014

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