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.
Subject(s)
Antineoplastic Agents/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Molecular Targeted Therapy/methods , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/analysis , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Receptor Protein-Tyrosine Kinases/analysis , Adult , Anaplastic Lymphoma Kinase , Antineoplastic Agents/administration & dosage , 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/enzymology , Male , Middle Aged , Prospective Studies , Protein Kinase Inhibitors/administration & dosage , Protein-Tyrosine Kinases/drug effects , Pyrazoles/administration & dosage , Pyridines/administration & dosage , Receptor Protein-Tyrosine Kinases/drug effects , Recurrence , Reverse Transcriptase Polymerase Chain Reaction , Treatment OutcomeABSTRACT
We report an unusual case of a primary osteosarcoma of the lung in an asymptomatic 77-year-old male, who underwent lobectomy with complete resection of the lung lesion. His pattern of relapse was to multiple lymph nodes. The first relapse was 11 weeks after lobectomy in subcarinal lymph nodes, confirmed on needle aspiration to be consistent with sarcoma. Given his excellent performance status, this was treated with radical radiotherapy to 70 Gy in 35 fractions with good control. He relapsed to other lymph node regions. A biopsy of the external iliac lymph node was done and revealed osteoid production, consistent with osteosarcoma. He received palliative radiotherapy to several nodal areas with good clinical response. We review the literature of this rare tumor with an unusual pattern of relapse.
