Therapeutic Vaccinations with p210 Peptides in Imatinib-Treated Chronic Myeloid Leukemia Patients: 10 Years Follow-Up of GIMEMA CML0206 and SI0207 Studies

<b>Background:</b> We previously showed that peptides encompassing the unique b3a2 or b2a2 breakpoint amino-acid sequence of oncogenic p210 induced peptide-specific T-cell responses in chronic myeloid leukemia (CML) patients. <b>Methods</b>: From 2007 to 2011, two multicenter peptide vaccine phase II studies, GIMEMA CML0206 and SI0207, enrolling overall 109 CML patients (68 b3a2 and 41 b2a2) with persistence of molecular disease during imatinib treatment, were carried out. Peptide vaccination schedule included the following: "immunization phase" (six vaccinations every 2 weeks); "reinforcement" phase (three monthly boosts) and "maintenance" phase (two boosts at 3-month intervals). GM-CSF (granulocyte-macrophage-colony-stimulating factor, sarmograstim) served as the immunological adjuvant. <b>Results</b>: The short-term results (at completion of vaccine protocol-12 months) and long-term follow-up are reported. All patients completed the vaccination schedule with no toxicity. After vaccinations, the BCR::ABL1 peptide-specific CD4+ T-cell response was documented in 80% of patients. In the short term, 30% of patients achieved a reduction in BCR::ABL1, while the majority showed stable molecular disease with fluctuations. The median follow-up since diagnosis and last vaccination are 18 and 10 years, respectively, with an overall survival (OS) rate at 18 years of 89%. In addition, 97/109 (89%) patients are alive, while 12/109 (11%) died of CML-unrelated reasons. Overall, 18/109 (16.5%) patients are in treatment-free remission (TFR) for a median time of 48 months. <b>Conclusions</b>: The long-term results of p210 peptide vaccinations in CML patients with persisting disease during imatinib treatment showed its feasibility, safety, absence of off-targets events, high OS and not negligible rate of successful TFR. Active immunotherapeutic approaches in CML patients with low disease burden, eventually employing newer vaccine strategies such as mRNA vaccines, may be reconsidered.

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Journal
Vaccines
Published
2025-04-16
DOI
https://doi.org/10.3390/vaccines13040419
Citations
2
Primary Topic
Chronic Myeloid Leukemia Treatments
Type
article
Field-Weighted Citation Impact
3.54
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article

Therapeutic Vaccinations with p210 Peptides in Imatinib-Treated Chronic Myeloid Leukemia Patients: 10 Years Follow-Up of GIMEMA CML0206 and SI0207 Studies

Sara Galimberti, Monica Bocchia, Giovanna Rege Cambrin, Andrea Patriarca et al.
2 citations
Vaccines
Chronic Myeloid Leukemia Treatments
3.54
article

Therapeutic Vaccinations with p210 Peptides in Imatinib-Treated Chronic Myeloid Leukemia Patients: 10 Years Follow-Up of GIMEMA CML0206 and SI0207 Studies

Sara Galimberti, Monica Bocchia, Giovanna Rege Cambrin, Andrea Patriarca, Vincenzo Sammartano, Michele Malagola, Fausto Castagnetti, Gabriele Gugliotta, Vladan Vučinić, Emanuele Cencini, Alfonso Piciocchi, Dietger Niederwieser, Monia Lunghi, Francesco Iuliano, Arianna Rughini, Alessandra Cartocci, Elisabetta Abruzzese, Cristiana Cafarelli, Marzia Defina, Tamara Intermesoli, Anna Sicuranza, Luigiana Luciano, Paola Pacelli, Alessandra Malato, Massimo Breccia, Antonella Russo Rossi, Mariella D’Adda
article en
2 citations

Abstract

<b>Background:</b> We previously showed that peptides encompassing the unique b3a2 or b2a2 breakpoint amino-acid sequence of oncogenic p210 induced peptide-specific T-cell responses in chronic myeloid leukemia (CML) patients. <b>Methods</b>: From 2007 to 2011, two multicenter peptide vaccine phase II studies, GIMEMA CML0206 and SI0207, enrolling overall 109 CML patients (68 b3a2 and 41 b2a2) with persistence of molecular disease during imatinib treatment, were carried out. Peptide vaccination schedule included the following: "immunization phase" (six vaccinations every 2 weeks); "reinforcement" phase (three monthly boosts) and "maintenance" phase (two boosts at 3-month intervals). GM-CSF (granulocyte-macrophage-colony-stimulating factor, sarmograstim) served as the immunological adjuvant. <b>Results</b>: The short-term results (at completion of vaccine protocol-12 months) and long-term follow-up are reported. All patients completed the vaccination schedule with no toxicity. After vaccinations, the BCR::ABL1 peptide-specific CD4+ T-cell response was documented in 80% of patients. In the short term, 30% of patients achieved a reduction in BCR::ABL1, while the majority showed stable molecular disease with fluctuations. The median follow-up since diagnosis and last vaccination are 18 and 10 years, respectively, with an overall survival (OS) rate at 18 years of 89%. In addition, 97/109 (89%) patients are alive, while 12/109 (11%) died of CML-unrelated reasons. Overall, 18/109 (16.5%) patients are in treatment-free remission (TFR) for a median time of 48 months. <b>Conclusions</b>: The long-term results of p210 peptide vaccinations in CML patients with persisting disease during imatinib treatment showed its feasibility, safety, absence of off-targets events, high OS and not negligible rate of successful TFR. Active immunotherapeutic approaches in CML patients with low disease burden, eventually employing newer vaccine strategies such as mRNA vaccines, may be reconsidered.

VaccinesVol. 13(4)
University of Siena (IT), University of Pisa (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT), Ospedale Vincenzo Cervello (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale Papa Giovanni XXIII (IT), Fondazione Gimema Onlus (IT), Presidio Ospedaliero (IT), University Hospital Leipzig (DE), Azienda Ospedaliera Universitaria Senese (IT), St. Eugenio Hospital (IT), Klinik und Poliklinik für Neurologie (DE), Ospedale San Luigi Gonzaga (IT), University of Bari Aldo Moro (IT), University of Naples Federico II (IT), University of Brescia (IT), Sapienza University of Rome (IT), University of Bologna (IT)
Good health and well-being
Openalex Percentile: Top 8%
Chronic Myeloid Leukemia Treatments
3.54
DOIOpen Access PDFOpenAlex
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