Complete molecular response in CML after p210 BCR–ABL1-derived peptide vaccination

Abstract

A 63-year-old woman with chronic myeloid leukemia who achieved a complete cytogenic response after 6 years of interferon-alpha went on to lose molecular response 2 years after treatment cessation. In this Case Study, Monica Bocchia and colleagues demonstrate the positive outcome in this patient following treatment with a therapeutic vaccine that consists of the p210 BCR–ABL1-derived peptide. The patient has maintained a complete molecular response for over 39 months. Background. A 63-year-old woman with chronic myeloid leukemia (CML) received treatment with interferon (IFN)-α for 6 years. After achieving a complete cytogenetic response that was repetitively documented, IFN-α treatment was stopped. Despite maintenance of a complete cytogenetic response, a progressive rise of the BCR–ABL1 transcript was detected and loss of major molecular response occurred about 2 years after stopping IFN-α therapy. Disease remained at molecular level. Investigations. Peripheral blood quantitative real-time PCR every 3 months and periodical bone marrow aspirate were performed to monitor disease. Diagnosis. Chronic-phase, Philadelphia-positive CML that was still detectable after complete cytogenic response 2 years after cessation of IFN-α therapy. Management. The patient was treated with a target immune approach receiving a therapeutic vaccine that consisted of an immunogenic 25-mer b2a2 breakpoint-derived peptide (CMLb2a2–25) with binding properties for several HLA–DR molecules. After nine boosts of vaccine the patient developed an adequate b2a2–25 peptide-specific CD4+ T-cell response and BCR–ABL1 transcript started to decline in peripheral blood. No hematological or extrahematological effects were documented during therapy. At the last evaluation, 39 months since vaccinations commenced, the patient is in complete molecular response with an undetectable level of BCR–ABL1 transcript both in peripheral blood and in bone marrow and she continues to receive boosts of vaccine every 3 months as the only treatment.