Clinical evaluation of BCR-ABL peptide immunisation in chronic myeloid leukaemia: results of the EPIC study

Peptides from the e14a2 Bcr-Abl junction will elicit T-cell responses in vitro. Here, 19 imatinib treated CML patients in first chronic phase were vaccinated with Bcr-Abl peptides spanning the e14a2 fusion junction, some of which were linked to the pan DR epitope PADRE to augment CD4+ T cell help. Six vaccinations were given over 9 weeks, together with sargramostim. All patients developed mild local reactions. T cell responses to PADRE were seen in all patients. Fourteen of 19 patients developed T cell responses to Bcr-Abl peptides. The development of an anti-BCR-ABL T cell response correlated with a subsequent fall in Bcr-Abl transcripts. No molecular benefit was seen in the 5 patients not in major cytogenetic response (MCR) at baseline. However, of the 14 patients in MCR at baseline, 13 developed at least 1 log fall in Bcr-Abl transcripts, though this occurred several months after completing vaccination, consistent with an effect at a primitive CML stem cell level. Vaccination may improve the fall in Bcr-Abl transcripts in patients who have received imatinib for more than 12 months. Bcr-Abl peptide vaccination may improve control of CML, especially in patients responding well to imatinib. Randomised trials are required to address this further.