Vaccines, Vol. 13, Pages 419: Therapeutic Vaccinations with p210 Peptides in Imatinib-Treated Chronic Myeloid Leukemia Patients: 10 Years Follow-Up of GIMEMA CML0206 and SI0207 Studies

Vaccines doi: 10.3390/vaccines13040419

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

Background: 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. Methods: 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. Results: 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. Conclusions: 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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Anna Sicuranza www.mdpi.com