Velcade makes a lot of myeloma cells sleepy

I am still stuck in a “busyness” quagmire, but a recent post by an MMA list member caught my attention, so I took some time today to do a bit of research. Here goes. Apparently, many myeloma patients do not respond to Velcade. And those who do eventually relapse. Well, it appears that researchers may have found out why.

 

A study on Velcade and its effects on myeloma cells was published in “Cancer Research” in February 2009 (see abstract: http://tinyurl.com/czsn2e). Velcade by itself doesn’t kill every single myeloma cell in the body. Indeed, it apparently creates the conditions whereby quite a number of them are able to slip into a state of dormancy, just like ants that go to sleep in order to survive harsh winters in Finland, e.g. When the dormant cells resume their active state, boom!, myeloma rears its ugly head again.

 

But it seems that when salubrinal, a “selective inhibitor of enzymes that dephosphorylate EIF 2-alpha” (don’t ask!),  is added to Velcade, there are very few survivors. In other words, these two drugs together are able to wipe out almost all the ants in Fin…I mean, almost the entire population of dormant myeloma cells.

When I was about 2/3 of the way through the abstract, the following thought popped into my head: why not try to figure out how we can use this bit of information to kill our dormant myeloma cells via natural treatments, or at least keep them in a state of dormancy? Or…is that what we are doing right now with curcumin etc.? I began to look into this very matter earlier today but soon realized that I need a bigger chunk of free time to do a semi-decent job. Ant…I mean, and I need the full study. More to come…

6 Comments

  1. Thank you Margaret for clarifying a very interesting article on Velcade and salubrinal combo. I had read the article and saved it and love when you give your clarifying take on things. thank you.

    off topic, I was just trying to install a new trackball point cover (not important what it is) on my laptop and all my juggling around must have stirred up my stored bookmarks and this interesting research that I had wanted to keep up with popped up on my screen. So I stopped the computer maintenance and started reading (my attention deficit is always in play).
    http://clinicaltrials.gov/archive/NCT00006219
    These pages show no publication and no recruitment and completed study in 2006 of stage II study, but this last page shows recruitment as of 2/20/2009. I don’t know if that means just followup of past study patients or a stage III study. John Lust at Mayo Clinic was in charge of the study at various Mayo clinics. I don’t know much about studies or how to get involved but this one interests me and I would not try DHEA unless under the care of a doctor.
    However, a 2005 publication is available (was given on ACOR list) seeming to indicate success.
    http://cancerres.aacrjournals.org/cgi/reprint/65/6/2269
    You have to click onto manual download for the PDF article.
    It is about chemoprevention for high risk myeloma. Not sure how DHEA and clarithromycin (biaxin) are chemo but apparently so. There was some minimal talk of this recently on the ACOR list but not much followup. However, the study is regarding the success of DHEA and clarithromycin on prevention for patients with high risk myeloma Since nothing has come of this since the close of study in 2006….. is there nothing to it? For some reason this study makes my heart beat a little faster, don’t know why, could just be too much coffee. I’ve never heard of success of stabilizing the m spike from those who have tried DHEA on its own, known to be an immune stimulant which I try to avoid for fear of stimulating the wrong thing. I try to stay with the immune modulators. But I like what I am reading. comments anyone???

  2. off specific topic but about curcumin:
    newly released article by Dr. Aggarwal
    Not sure how to get to it on-line, as a friend from the myeloma group sent me the PDF, but Google the label Aggarwal-TIPS-200
    or Pharmacological basis for the role of curcumin in chronic diseases

    Maybe you already have posted this, I’m a newbie here.
    Has anyone ever tried to gather data on the myeloma types correlated to success or lack of success with curcumin/ Just wondered. I know Don said it didn’t work for him.
    My patient’s type is the dreaded IGA and Lambda.

    He has finally agreed to try curcumin but only very slowly. We just got his genetic results and there are three bad markers in that information, so I am pretty sure they are moving his classification from smoldering, perhaps all the way to 3, and probably contemplating a transplant faster than I can get him up to a full dose of curcumin. His immediate problem is extreme pain requiring back damage repair. His PET scan looked PERFECT and he has no M-spike, but his Beta2microglobulin went from okay to bad between Dec. and March.

    Would anyone care to respond about their IG type and Lambda/Kappa in relation to their success with curcumin, or is that info already somewhere in Margaret’s excellent archives?

  3. To Julie
    From my prospective beta-2-microglobulin is the most important marker in multiple myeloma. The relation what are you looking is probably no there. At least I do not see it.
    Peter 06

  4. Peter,
    I understand what you are saying about mm type and curcumin and I’d love to think the curcumin works on even the evil IGA Lambda as well as it has for other types, so I’ll gladly make the same assumption.
    I’m not sure what your reference to the B2M means. Do you mean that the patients who don’t respond to curcumin are more likely those with high B2M, or are you just mentioning that you think over all the B2M is more predictive than the type (eg Lambda, Kappa etc)? I’ve seen some percentages on the types and which are associated with better prognosis, independent of the B2M. Although we were told initially that the B2M was the most important indicator. At the time we were quite happy to hear that. Initially Van’s was in the normal range quite comfortably. It kind of freaked me out that it went to 1.98 in just three months (by the second test, after we escaped the two months in the hospital and traveled to Mayo). I wondered if the radiation on the plasmacytoma made the cancer more active.

    So maybe the question is whether success correlates with their B2M?

    I’d sure like to think cucumin might work for my husband, I’m bucking his doctor and the patient himself to get him to try it. Ridicuolously, part of the argument rests on not using Advil on top of his prescription pain meds (methadone, dilaudid, Lyrica) – there have to be dozens of alternatives, but somehow his doctor is convinced that he needs Advil (an NSAID, not compatible with curcumin). He is in terrible pain from compression fractures in his L-5 where he had radiation for a plasmacytoma and awaiting rod implant surgery.
    The pain has totally limits his mobility and trashed his quality of life, so the cancer has become secondary to him.

    More details than you needed, I’m sure, but I know I’m going to have a tough time keeping him on the curcumin and I wish I had a crystal ball to know the effects will show up in his blood numbers in a month.

  5. To Julie
    B2M is the best marker overall independent from Lambda or Kappa free light chains. Lambda is worse then Kappa. IgA is worse then IgG. Plasmacytoma is better then myeloma, but specific locations like spine may make it difficult. 1.98 is not big number for myeloma, but the same number for plasmacytoma means that active disease is concentrated to smaller area. Radiation may aggravate cancer, but at the time kills cancer. This is delicate balance. I am not so sure if curcumin will work, but I wonder if somebody else could answer that. The information what are you looking for is probably not on this web page.
    Peter 06

  6. I had just finished Velcade when I found curcumin, looking for something to gain back bone. I was dxed with MM stage 3B in Dec 96, twelve years ago. I have kappa light chain IgG. I started curcumin in mid January, but the cancer came back in Feb. My onc was deeply concerned and wanted me to go on doxil, but I declined and chose Velcade once again, with curcumin. I had labs today to see if V is working with the curcumin and very low dose prednisone. It had barely budged last time. So for me, so far, curcumin has not been successful of MM, but it definitely helped my back pain (a have a broken back and three thinline fracures in the spine, plus a broken hip and a skull that looks like swiss cheese, even from the outside.

    I continue to take the curcumin for other things, but have to admit that it has not yet worked for the MM, although I take 4 grams a day.

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