CML is caused by the breakage and swapping of chromosomes 9 and 22, which results in a shortened chromosome called the Philadelphia chromosome. Cells with the abnormal chromosome make a protein that encourages aberrant growth and division. Patients with CML can be treated with a drug called imatinib or interferon alfa. Treatment with imatinib can lead to complete cytogenetic remission, where no Philadelphia chromosomes are detected during cell division. However, a complete molecular response, where there is no evidence of the protein produced by the Philadelphia chromosomes, is rare.
Monica Bocchia (University of Siena, Italy) and colleagues tested whether a vaccine that targets a protein derived from the Philadelphia chromosome could help to eradicate the disease in patients. The investigators enrolled 16 individuals (10 patients on imatinib and 6 on interferon) with stable, but detectable disease into the trial. Patients were given one dose (six injections) of the protein vaccine every 2 weeks while they continued their conventional treatment. Patients were assessed before vaccination and after three and six doses for evidence of the disease.
Nine patients on imatinib showed progressive reduction of their residual disease after three and six doses of the vaccine with five patients reaching complete cytogenetic remission. Three of the five patients also obtained undetectable disease at a molecular level. Of the six patients on interferon alfa, five showed a reduction of their stable disease during vaccinations, with two reaching complete cytogenetic remission.
Dr Bocchia comments: "Our preliminary data suggest that the addition of this vaccine to patients treated with conventional treatment might favour further reduction of the residual disease and increase the number of patients who reach a molecular response, the best surrogate of cure for those with chronic myeloid leukaemia.
"Studies that focused on improving the assessment of residual disease after vaccination, including larger numbers of patients as well as longer follow-up are under way to assess definitively the role of this vaccine against leukaemia."
In an accompanying commentary Saswati Chatterjee and Dr K.K. Wong (City of Hope National Medical Centre, California, USA) and colleagues comment that although almost identical to other previous studies on this vaccine, Bocchia's research is the first to show a clinical response.
Dr Chatterjee concludes: "Given the ease of administration, lack of toxicity, and early promise of efficacy, vaccine development against the fusion protein or other CML specific antigens appears to be a reasonable avenue for further investigation. In the meantime, we will eagerly await the results of disease free-survival in the vaccinated group and confirmatory studies by other investigators in the field."
Contact: Dr Monica Bocchia, Department of Hematology, Ospedale A Sclavo
Via Tufi 153100 Siena, Italy. T) 39-057-758-6798 bocchia@unisi.it
(comment) Dr Saswati Chatterjee, Division of Virology and Dr K.K. Wong, Division of Hematology & Hematopoietic Cell Transplantation
City of Hope National Medical Center, Duarte, CA 91024, USA. T) 1-626-301-8436 schatterjee@coh.org
Journal
The Lancet