title: Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma.
abstract: 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.
authors.affiliation: III Medical Department, Technische Universität München, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Heidegger
authors.affiliation: Nuclear Medicine Department, Technische Universität München, Munich, Germany.
authors.forename: Ambros J
authors.initials: AJ
authors.lastname: Beer
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Geissinger
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: III Medical Department, Technische Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.affiliation: III Medical Department, Technische Universität München, Munich, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ringshausen
authors.affiliation: III Medical Department, Technische Universität München, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
keywords: DHAP; anaplastic large cell lymphoma (ALCL); anti-CD30 drug conjugate; combined therapy; refractory relapsed lymphoma