Vaccine for Chronic Myelogenous Leukemia Shows Promise

[Guest guest]

I think we may have read this already, but it is coming across on my

newswire again today, so I thought I'd post it.

Good reading!

Cheryl-Anne

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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