Crizotinib in Anaplastic Large-Cell Lymphoma

Crizotinib in Anaplastic Large-Cell LymphomaTo the Editor: Crizotinib, an inhibitor of the anaplastic lymphoma kinase (ALK) tyrosine kinase, is active in non-small-cell lung cancers that have ALK expression. 1 ALK is fused to several partner genes (mainly the gene encoding nucleophosmin) in the majority of anaplastic large-cell lymphomas (ALCLs).ALK tyrosine kinase activity represents the driver alteration in this disease. 2ALK-positive ALCLs are highly responsive to cytotoxic drugs.However, relapses occur and require salvage therapy.We treated two patients who had relapsed ALK-positive ALCL with crizotinib at a dose of 250 mg twice daily.No glucocorticoids or other drugs with antineoplastic activity were allowed.Patient 1, a 26-year-old woman, received seven cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-15) and had a partial response at 1 month.She was subsequently treated with standard salvage combination chemotherapy regimens in an attempt to prepare for autologous bone marrow transplantation.However, relapse occurred within 2 to 3 weeks after each regimen.Pretreatment evaluation included fever (temperatures >38°C), cervical and inguinal adenopathy, and positive results on positron-emission tomographic (PET) and computed tomographic (CT) images of paraaortic and iliac nodes; bone marrow aspiration showed 3% of cells with ALK rearrangement.She had a score of 3 on the Eastern Cooperative Oncology Group (ECOG) performance scale (indicating confinement to bed or chair 50% or more of waking hours).After the initiation of crizotinib, Patient 1's fever disappeared within 48 hours; by day 7, all palpable adenopathy had resolved.PET and CT images and bone marrow aspiration performed at 28 days showed complete regression of previous