Vaccine for Chronic Myelogenous Leukemia Shows Promise

According to the results of a study recently reported in the Lancet, researchers from Italy have reported that a new vaccine may eradicate residual leukemia cells left in the bone marrow after treatment with Gleevec® or interferon for chronic myeloid leukemia (CML).

Chronic myelogenous leukemia (CML) is a blood disease characterized by excess production of white blood cells. This disease is associated with a chromosomal abnormality called the Philadelphia chromosome. Some patients have what is called a BCR-ABL-derived p210 fusion protein which can be recognized by the body as “non-self” and can potentially be a target for immune therapies. For the past several years, all newly diagnosed patients have been treated with a drug called Gleevec® (imatinib), which results in clinical remissions and disappearance of the Philadelphia chromosome in most cases. There is also evidence that Gleevec® improves survival over the previous best therapy, which was interferon. However, most patients treated with Gleevec® still have residual leukemia as detected in a molecular test called polymerase chain reaction (PCR). Younger patients who fail Gleevec® therapy are usually treated with an allogeneic stem cell transplant, which is the only treatment that truly eradicates the leukemic clone. However, this is a risky procedure and researchers are seeking alternative immune therapies for patients with CML.

In this recent study, researchers investigated the role of a vaccine as a targeted treatment for CML. In order to be eligible for this study, patients had to have specific histocompatibility (HLA) types and have the type of CML targeted by the vaccine. Sixteen patients diagnosed with CML were enrolled. Each patient was determined to have stable disease and had completed a minimum of 12 months of treatment with Gleevec® or 24 months of treatment with interferon, and had no further reduction in residual disease within six months of enrollment. All participants were treated with six injections of a protein-based vaccine that was target-specific for CML. Response was measured by evaluating the patient’s immune response, as well as the disease response.

Ten of the patients in this study had been treated with Gleevec®, nine of whom had an average of 10 months of stable disease and one patient started the study with a stable, complete clinical response. All patients who had been treated with Gleevec® showed an improvement at the cellular level after receiving the six vaccinations, with five patients reaching a complete clinical response. Interestingly, three of the five were found to have undetectable levels of disease by PCR.

These authors reportred that all 10 Gleevec® and 5 of 6 interferon patients had decreased numbers of Philadelphia chromosome positive cells after treatment. The complete cytogenetic response rate was 7 of 16 and 4 had complete molecular remissions as tested by PCR. Toxicities associated with the vaccines were considered minimal. Eleven of the 16 patients had a positive skin test to the vaccine indicating successful vaccination.

A discussion among the researchers and other colleagues reveals that the success of this study, along with the lack of toxicity, supports the development of immune strategies for the treatment of CML. The current thinking is that cure of CML will be associated with complete eradication of the CML clone as measured by sensitive PCR testing. Immune therapies appear to be the best approach for eradication of minimal residual disease. Patients with CML who have not had a complete molecular remission to Gleevec® should seek out experimental treatments designed to eradicate the last leukemia cell.

References:

Wong K, Chatterjee S. Vaccine Development for Chronic Myelogenous Leukemia. Lancet. 2005; 365: 631-632.

Bocchia M, Gentili S, Abruzzese E. et al. Effect of a p210 Multipeptide Vaccine Associated With Imatinib or Interferon in Patients with Chronic Myeloid Leukemia and Persistent Residual Disease: a Multicenter Observational Trial. Lancet 2005; 365: 657-662.

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