983P - Excellent quality of lives for previously treated adult T-cell leukemia/lymphoma patients after autologous dendritic cell vaccine therapy targeting...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Leukaemia
Lymphomas
Cancer Immunology and Immunotherapy
Presenter Youko Suehiro
Citation Annals of Oncology (2014) 25 (suppl_4): iv327-iv339. 10.1093/annonc/mdu339
Authors Y. Suehiro1, T. Iino2, A. Hasegawa3, N. Watanabe4, M. Matsuoka5, R. Tanosaki6, A. Utsunomiya7, I. Choi1, M. Shiratsuchi8, T. Teshima9, K.A. Akashi10, M. Kannagi3, N. Uike1, J. Okamura11
  • 1Hematology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 2Center For Advanced Medicine Innovation, Kyushu University, Fukuoka/JP
  • 3Immunotherapeutics, Tokyo Medical and Dental University, Tokyo/JP
  • 4Institute Of Medical Science, University of Tokyo, Tokyo/JP
  • 5Institute For Virus Research, Kyoto University, Kyoto/JP
  • 6Clinical Laboratory Division, National Cancer Center Hospital, Tokyo/JP
  • 7Hematology, Imamura Bun-in Hospital, Kagoshima/JP
  • 8Medicine And Bioregulatory Science, Kyushu University, Fukuoka/JP
  • 9Hematology, Hokkaido University, Sapporo/JP
  • 10Medicine And Biosystemic Science, Kyushu University, Fukuoka/JP
  • 11Institute For Clinical Research, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP

Abstract

Aim

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type-1 (HTLV-1)-infected T-cell malignancy with extremely poor prognosis due to frequent relapse. Among HTLV-1 antigens, the viral regulatory protein Tax is widely recognized as a target of cytotoxic T lymphocytes (CTLs). We investigated the safety and feasibility of Tax peptide-pulsed dendritic cell (Tax-DC) vaccine therapy administered to augment Tax-specific CTL responses in ATL patients.

Methods

Three previously treated acute-type ATL patients possessing HLA-A*0201, A*2402 and/or A*1101 in stable condition were enrolled in the study. Autologous monocyte-derived dendritic cells (DCs) that exhibited the mature phenotype were pulsed with Tax peptides corresponding to the major epitopes of Tax-specific CTL previously identified from ATL patients who received stem cell transplantation. The vaccine protocol consists of three subcutaneous injections of Tax peptide-pulsed DC at 2-week intervals in a total 8-week observation period to assess adverse events. The primary endpoint of the study was to evaluate safety and feasibility of Tax-DC vaccine.

Results

DC vaccine-related toxicities were grade 1 or 2 and were considered relatively mild, and non-hematological toxicity was acceptable. Two patients achieved partial remission and one obtained stable disease. The performance status improved after vaccination in all patients and two of them are currently alive without any additional chemotherapy for 17 and 12 months respectively, while the third patient developed slowly progressive disease, although additional therapy was not required until 14 months after vaccination. In all three patients, the level of HTLV-1 proviral load in the peripheral blood mostly revealed below 100 copies per 1,000 PBMCs during the observation period, and Tax-specific CTL responses were observed with a peak at 16-20 weeks.

Conclusions

The good quality of lives and long-term treatment-free survival after vaccination observed in this first pilot study indicates that the Tax-DC vaccine is a safe and promising long-lasting maintenance therapy for ATL.

Disclosure

All authors have declared no conflicts of interest.