Abstract
T cell prolymphocytic leukemia (T-PLL) is a rare, mature T cell neoplasm with distinct features and an aggressive clinical course. Early relapse and short overall survival are commonplace. Use of the monoclonal anti-CD52 antibody alemtuzumab has improved the rate of complete remission and duration of response to more than 50% and between 6 and 12 months, respectively. Despite this advance, without an allogeneic transplant, resistant relapse is inevitable. We report seven complete and one partial remission in eight patients receiving alemtuzumab and cladribine with or without a histone deacetylase inhibitor. These data show that administration of epigenetic agents can overcome alemtuzumab resistance. We also report epigenetically induced expression of the surface receptor protein CD30 in T-PLL. Subsequent treatment with the anti-CD30 antibody-drug conjugate brentuximab vedotin overcame organ-specific (skin) resistance to alemtuzumab. Our findings demonstrate activity of combination epigenetic and immunotherapy in the incurable illness T-PLL, particularly in the setting of previous alemtuzumab therapy.
Copyright © 2015, American Association for the Advancement of Science.
Publication types
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Clinical Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Alemtuzumab
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Antibodies, Monoclonal, Humanized / pharmacology
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Antibodies, Monoclonal, Humanized / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Brentuximab Vedotin
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Cell Proliferation / drug effects
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Chromatin / metabolism
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics*
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Epigenesis, Genetic* / drug effects
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Female
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Gene Expression Regulation, Leukemic / drug effects
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Humans
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Immunoconjugates / pharmacology
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Immunoconjugates / therapeutic use
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Ki-1 Antigen / metabolism
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Leukemia, Prolymphocytic, T-Cell / blood
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Leukemia, Prolymphocytic, T-Cell / drug therapy
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Leukemia, Prolymphocytic, T-Cell / genetics*
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Leukocyte Count
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Male
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Middle Aged
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Oligonucleotide Array Sequence Analysis
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Promoter Regions, Genetic / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Real-Time Polymerase Chain Reaction
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STAT5 Transcription Factor / genetics
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Skin / drug effects
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Skin / pathology
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Treatment Outcome
Substances
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Antibodies, Monoclonal, Humanized
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Chromatin
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Immunoconjugates
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Ki-1 Antigen
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RNA, Messenger
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STAT5 Transcription Factor
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Alemtuzumab
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Brentuximab Vedotin