Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 2517
© 2004 American Society of Clinical Oncology

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Abstract

Peptide-vaccine treatment associated with imatinib in patients with residual CML disease is able to induce both immunologic response and molecular remission

Tor Vergata University, S. Eugenio Hospital, Rome, Italy; Hematology, Siena, Italy; Hematology, Catanzaro, Italy

2517

Background: The main objective in the intent to "cure" chronic myeloid leukemia (CML) is to obtain complete cytogenetic (CCR) and molecular remission (MR). Interferon-A and Imatinib have only partially achieved this goal. An alternative approach to target the residual disease is specific immunotherapy. We associated Imatinib and immunogenic peptides derived form the p210 b3a2 fusion protein in patients on Imatinib with stable disease at cytogenetic level. Methods: Ten patients with CML in chronic phase on Imatinib for a median time of 15.5 months (range 12–24) were enrolled. All patients were on their +2nd line treatment being resistant or refractory to IFN-based previous therapies. They presented with an unchanged residual disease from a median of 10 months (range 6–18) consisting of bone marrow Ph+ metaphases ranging from 2–43%. Vaccination included GM-CSF pre treatment and administration of 500 mcg of 5 different length(8–25 aa)peptides mixture of restricted for HLA class I and class II molecules, associated with immunologic adjuvant QS-21. All patients were tested with peptide mixture at 25 mcg dosage in absence of adjuvants (DTH) prior to vaccine to evaluate their sensitivity; all of them resulted negative. The immunotherapy consisted on 6 vaccinations every 2 weeks and 2 additional boosts at +4 and +10 months. Cytogenetic, FISH and molecular biology, immunologic response, cytokine production and immunophenotype were analyzed during treatment. Results: All patients showed a variable degree of progressive reduction of their residual Ph+ metaphases after 3, 6 vaccinations (3 months) and boosts, with 7/9 becoming CCR and 4/6 evaluable achieving MR. All patients presented with some degree of DTH indicating the in vivo "recognition" of peptides by effector T cells. Conclusions: These data suggest that the addition of b3a2-specific vaccine may have a synergistic effect with Imatinib favouring a rapid reduction of minimal residual disease and increasing the number of patients that reach MR.

No significant financial relationships to disclose.

Abstract presentation from the 2004 ASCO Annual Meeting