OncoTargets and Therapy (Jun 2014)
Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma
Abstract
Simon Heidegger,1 Ambros Beer,2 Eva Geissinger,3 Andreas Rosenwald,3 Christian Peschel,1 Ingo Ringshausen,1 Ulrich Keller11III Medical Department, 2Nuclear Medicine Department, Technische Universität München, Munich, Germany; 3Institute of Pathology, University of Würzburg, Würzburg, GermanyAbstract: Anaplastic large cell lymphoma (ALCL) is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone) was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.Keywords: anaplastic large cell lymphoma (ALCL), refractory/relapsed lymphoma, anti-CD30 drug conjugate, DHAP, combined therapy