I don’t think I’ve ever slept as much as I did this weekend. Coming off my first pomalidomide/dex maintenance cycle, I hit the wall. If I didn’t know better I’d say my GI issues are improving. Time will tell. It’s been two steps forward, one back.

I feel rested and ready to rock ‘n roll today. What a week last week! I haven’t written about it much, but daratumumab has the potential to be more than just another new drug. If dara (or another immunotherapy) can soften up targeted myeloma cells, maybe researchers can begin overcoming the riddle of drug resistance.

Or maybe myeloma researchers can make progress overcoming drug resistance through a side door like the one Danny is investigating. Here is Danny Parker’s third installment investigating links between blood sugar levels and a related drug, metformin:

Low Glucose Environment and the Reduction Myeloma Mutation Rates

There is no conclusive evidence that diabetes is associated with the likelihood of developing myeloma as seen in a meta-analysis by Khan et al. (2008):

http://www.ncbi.nlm.nih.gov/pubmed/18443270/

However, once one has myeloma, then we see that having high blood sugar and diabetes appears an adverse risk factor for myeloma progression. And there are physiological reasons for that association.

Blood sugar graph

The propensity of myeloma clones to mutate (mutagenesis) is a known issue with the development by the disease of resistance to drugs currently used for treatment. An article if from the Hematology Times from March 2014 showed that a low glucose environment is associated with a reduced proliferation of myeloma cell lines—more mutations is usually a bad thing. The myeloma mutates to find a way around the chemotherapy drugs we use to control it:

http://www.hematologytimes.com/p_article.do?id=3986

As described earlier, clinical outcomes in multiple myeloma with blood glucose levels has also shown association in existing research. Thus, there is accumulating evidence that even normal high serum glucose may be a risk factor for developing myeloma and other cancers:

http://www.researchgate.net/profile/Hans_Concin/publication/7222680_Fasting_blood_glucose_and_cancer_risk_in_a_cohort_of_more_than_140000_adults_in_Austria/links/00b7d529ce4d3486a2000000.pdf

Moreover, data from Chou et al., (2012) shows that diagnosed myeloma patients who either have or develop diabetes over the course of the disease have worse survival than those that do not:

http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2012.01828.x/abstract;jsessionid=F79ABE048151E403E60F92B6A992546F.f01t02

Thus, there is a strong physical basis for the reported influence of metformin associated with hematological malignancies. Metformin downregulates Insulin like growth factor-1 (IGF-1)- a known growth factor for myeloma cells. Moreover, an extensive research literature shows that obesity is associated with MGUS and also with the likelihood of developing myeloma.

Finally, use of metformin has also been associated with lower risk of other cancers in other epidemiological studies. Three supporting studies among many:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334849/

https://www.ncbi.nlm.nih.gov/pubmed/20980415/

Zhi et al., (2013)http://www.ncbi.nlm.nih.gov/pubmed/23945247

Tomorrow Danny makes a case for using metformin as an anti-myeloma therapy. While the FDA is busy approving new molecules to battle myeloma, I’m hoping existing drugs–used primarily for other uses–may be able to contribute and help us, too.

Feel good and keep smiling! Pat