PR1 Vaccine Elicited Immunological Response after Hematopoietic Stem Cell Transplantation Is Associated with Better Clinical Response and Event-Free Survival.
2007; Elsevier BV; Volume: 110; Issue: 11 Linguagem: Inglês
10.1182/blood.v110.11.577.577
ISSN1528-0020
AutoresMuzaffar H. Qazilbash, Eric Wieder, Peter F. Thall, Xuemei Wang, Rosa L. Rios, Sijie Lu, Shreya Kant, Sergio Giralt, Elihu H. Estey, Jorge E. Cortés, Krishna V. Komanduri, Richard E. Champlin, Jeffrey J. Molldrem,
Tópico(s)Monoclonal and Polyclonal Antibodies Research
ResumoAbstract Background: PR1 peptide has been established as a human myeloid leukemia-associated antigen. We studied PR1 peptide vaccine in a phase I/II clinical trial in HLA-A2 + patients with AML, MDS and CML. To address whether prior HSCT or prior use immunosuppressive drugs would prevent PR1-induce cytotoxic T lymphocyte (PR1-CTL) immunity after vaccination with PR1 peptide vaccine, we studied the outcome in 20 patients with a prior HSCT, who were treated on the PR1 vaccine trial. Methods: Twenty patients (13 with AML or MDS, 7 with CML) were vaccinated at a median time of 9.5 months (range: 1–220) after HSCT. Sixteen patients had received a prior allogeneic HSCT (12 had allogeneic related, 3 had allogeneic unrelated, and 1 had syngeneic) and 4 patients had a prior autologous HSCT. At the time of vaccination, 5 patients were in CR, and 15 had measurable disease. Patients could not receive systemic immunosuppressive therapy for at least 4 weeks prior to vaccination, and had to be free of acute or chronic GVHD requiring systemic therapy. The vaccine was given subcutaneously every 3 weeks for a total of 3 injections at one of three dose levels: 0.25, 0.5 and 1.0 mg. GM-CSF at a dose of 75 mg was injected subcutaneously into the same site. Immune response to the vaccine (IRV) was defined as > 2-fold increase in PR1-CTL by PR1/HLA-A2 tetramer assay. Results: After a median follow up of 56.5 months (range: 27–89), toxicity was limited to grade I/II injection site reactions in 7 (35%) patients. IRV were observed in 11/20 (55%) patients. Nine of 11 (82%) IRV+ patients versus 1 of 9 (11%) IRV- patients had clinical responses (p = .005). Median event-free survival (EFS) was 23.8 months in IRV+ patients versus 1.9 months in IRV- patients (p=0.03). Median overall survival (OS) in IRV+ patients has not yet been reached vs. 40 months in IRV- patients (p = 0.08). Only 2 patients with pre-existing, limited chronic GVHD experienced a mild exacerbation within 3 months of vaccination, which was controlled with topical steroids. PR1-CTL were enriched in central memory phenotype (TCM) that persisted up to 4 years in clinical responders. Univariate and multivariate Cox proportional hazards analyses showed a low pre-vaccine bone marrow blast count (<10%) was associated with a lower risk of progression (p=0.001 and 0.001, respectively). Type of HSCT, interval between HSCT and PR1 vaccine, PR1 dose level and disease status at HSCT did not have a significant impact on EFS or OS. Conclusion: PR1 vaccine produced PR1-CTL in 11/20 (55%) patients after HSCT. IRV was associated with significantly better clinical response and longer EFS. Figure Figure
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