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: Tait D Shanafelt, Alan G Ramsay, Clive S Zent, Jose F Leis, Han W Tun, Timothy G Call, Betsy LaPlant, Deborah Bowen, Adam Pettinger, Diane F Jelinek, Curtis A Hanson, Neil E Kay
• Journal: Blood (Blood) Vol. 121 Issue 20 Pg. 4137-41 (May 16 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23493782 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Thalidomide
• Lenalidomide

Topics

• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Cohort Studies
• Combined Modality Therapy
• Consolidation Chemotherapy
• Humans
• Immunological Synapses (drug effects, physiology)
• Immunotherapy (methods)
• Lenalidomide
• Leukemia, Lymphocytic, Chronic, B-Cell (immunology, physiopathology, therapy)
• Neoadjuvant Therapy
• Recovery of Function (drug effects, immunology)
• Retrospective Studies
• T-Lymphocytes (drug effects, immunology, pathology)
• Thalidomide (administration & dosage, analogs & derivatives)
• Time Factors
• Treatment Outcome