title: Long-term repair of T-cell synapse activity in a phase II trial of chemoimmunotherapy followed by lenalidomide consolidation in previously untreated chronic lymphocytic leukemia (CLL).
abstract: Immunotherapy that facilitates endogenous T-cell activity has the potential to target therapy-resistant tumor clones. In vitro studies have demonstrated that lenalidomide repairs the T-cell immunologic synapse defect in chronic lymphocytic leukemia (CLL). Pentostatin, cyclophosphamide, and rituximab (PCR) in CLL is clinically active with modest toxicity, indicating suitability of this chemoimmunotherapy (CIT) platform for combination with immunotherapy. Here we report on a trial of PCR followed by lenalidomide consolidation. Of 34 patients who received lenalidomide, 24% improved their quality of response and 4 patients converted to minimal residual disease negative status. Retrospective comparison to a historical PCR trial indicated that lenalidomide consolidation extends time to progression requiring salvage therapy. Longitudinal analysis showed that antitumor T-cell immune synapse activity improved post-PCR and was further enhanced after lenalidomide consolidation. These novel data showing repair of T-cell defects provide proof-of-principle that lenalidomide-based consolidation after CIT could have a beneficial clinical and immunologic role in CLL.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA. hanafelt.tait@mayo.edu.
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Alan G
authors.initials: AG
authors.lastname: Ramsay
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Jose F
authors.initials: JF
authors.lastname: Leis
authors.forename: Han W
authors.initials: HW
authors.lastname: Tun
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.forename: Betsy
authors.initials: B
authors.lastname: LaPlant
authors.forename: Deborah
authors.initials: D
authors.lastname: Bowen
authors.forename: Adam
authors.initials: A
authors.lastname: Pettinger
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D006801:Humans; D054992:Immunological Synapses / Q000187:drug effects / Q000502:physiology*; D007167:Immunotherapy / Q000379:methods; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D020360:Neoadjuvant Therapy; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide