This morning the newswires (HT Mike Huckman) are full of the BioSante (formerly Cell Genesys) news on their leukemia vaccine, GVAX, which is being tested to see whether it is a viable approach for eradication of minimal residual disease. Accordingly, BioSante announced:

"Positive results of a human clinical study that show that its GVAX Leukemia vaccine may be able to reduce or eliminate the last remaining cancer cells in some chronic myeloid leukemia (CML) patients taking the drug Gleevec (imatinib mesylate). All patients enrolled in the trial used Gleevec for at least one year and still had cancer cells present. The study was conducted by researchers at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, led by Hyam Levitsky, M.D., professor of oncology, medicine and urology at the Cancer Center. The research was funded by the National Institutes of Health."

Currently standard of care for CML is daily treatment with an oral tyrosine kinase inhibitor (TKI), imatinib (Gleevec), with the option of two second generation TKI's nilotinib (Tasigna) and dasatinib (Sprycel) being available if the imatinib fails.  All three of these drugs are effective at inhibiting the enzyme associated with the gene BCR-ABL, which occurs in every CML patient and essentially shut off production of the excess white blood cells so that the cells stop growing and eventually die.

There are various degrees of response with TKIs and at the American Society of Hematology meeting in December, Tim Hughes from Adelaide presented the concept of a safe haven as you can see from the chart below:

Hughes_MMR
Source: Dr Tim Hughes, Adelaide, Australia

Obviously, the deeper the response, the more likely a patient would attain a major molecular response (MMR) and provide a safe haven from treatment relapse.

The important question then becomes one of how low should one go in order to 

  • Optimise treatment response and 
  • Provide enough protection without increasing side effects?

Going back to the quote at the top of the post about GVAX, we can see that the researchers goal was to eliminate minimal residual disease (MRD) and kill all detectable cancer cells below what is currently possible with TKI therapy.  

In the article published in Cancer Clinical Research (free PDF download courtesy of AACR), it seems that according to the researchers

"Thirteen patients had a progressive decline in disease burden, 8 of whom had increasing disease burden before vaccination. Twelve patients achieved their lowest tumor burden measurements to date following vaccine, including seven subjects who became PCR-undetectable."

Now while this is very good news to hear that it can be accomplished, the numbers are very small and we don't have any data whatsoever yet to prove that achieving the nirvana of MMR is actually necessary for the majority of CML patients. None, nada, zilch.  We also do not have any idea from the article how durable the vaccine results will be yet as there may be an attenuation of response over time.

We do know from the IRIS updates that newly diagnosed people with CML now have a much longer life expectancy of around 7+ years on average when treated with imatinib.  Stem cell transplants are curative in some patients, but that decision is fraught with a risk-benefit trade-off of 20% procedure related mortality and the risk of graft-versus-host disease and other long term complications afterwards.

In conclusion: 

It will be interesting to see what impact this vaccine will have in the long term in terms of improved survival for people living with CML and whether future research will demonstrate a clear need to eliminate minimal residual disease below what is currently possible.  These are promising results and I look forward to seeing more data over the next few years as the answers evolve.  The ultimate goal is always to find a cure but whether this approach will help achieve that remains to be seen.


ResearchBlogging.org
Smith, B., Kasamon, Y., Kowalski, J., Gocke, C., Murphy, K., Miller, C., Garrett-Mayer, E., Tsai, H., Qin, L., Chia, C., Biedrzycki, B., Harding, T., Tu, G., Jones, R., Hege, K., & Levitsky, H. (2010). K562/GM-CSF Immunotherapy Reduces Tumor Burden in Chronic Myeloid Leukemia Patients with Residual Disease on Imatinib Mesylate Clinical Cancer Research, 16 (1), 338-347 DOI: 10.1158/1078-0432.CCR-09-2046