[Multibilly]

Re: FDA approves Empliciti (elotuzumab)

by Multibilly on Fri Dec 04, 2015 8:09 pm

Mike,

Regarding your earlier question about how elo works with NK cells, this video might help you better understand it. The relevant part of the video starts about 13 minutes in.

http://mp.peerviewpress.com/player/56675/4945/2#2

[JPC]

Re: FDA approves Empliciti (elotuzumab)

by JPC on Sat Dec 05, 2015 9:41 am

Good morning:

I think I might have learned a little terminology and details based on the homework given to me by Cheryl, Multibilly, and started by MikeB, so I will try to report back . I earlier got hung up on Elo's claim that it was the ONLY approved Mab with immunostimulatory properties. To me a suspicious claim given that it was approved after Dara. Now sometimes I try to get into the various diagrams on the inner working of cells, and since I am not trained in the biological sciences, my eyes glaze over. Sometimes with a little bit of help, I understand some of it. But I had understood that on a high level, all monoclonal antibodies (Mab's) are immunotherapies that re-activate the bodies own immune system in suppressing the multiple myeloma by identifying "targets" on the surface of multiple myeloma cells so that the immune system can "see" the multiple myeloma cells better, and attack them.

I think that Cheryl nailed it in that Dara has a process (different from Elo's) that also stimulates the immune system into action. Elo, however, has been shown to raise the level of Natural Killer (NK) cells, in addition to "tagging" the CS-1 positive (aka SLAMF-7) cells. This means of action (increase in NK levels), specifically cited in the FDA approval is the basis of the claim by Bristol Myers Squibb. So far I am just re-stating what Cheryl stated in my own words. After studying the issue, I am still disliking the use of the word "ONLY", even more so. Now, apart from that, I like both Elo and Dara very very much. The best part for both is that doctors reported, based on early signals, that both Elo and Dara (and maybe all future Mab's) neutralize cytogenetic abnormalities, and in my wife's case, she is t 4,14 positive.

Here is a quote from Dr. Lonial, in one of the links cited by Multibilly:

"Of note, patients at high risk as a result of the 19p deletion or t(4;14) genetic abnormalities had a similar benefit from elotuzumab as patients with average risk. These patients typically have less benefit from conventional therapies, Dr Lonial noted."

I have heard Dr. Richardson note the same observation for data from elo trials at Dana Farber. And I have heard Dr. Langren state that with respect to combo's, that it will be very beneficial to match up surface targeted therapies with IMID's and PI's, which work on the interior of multiple myeloma cells. He hypothesized that the combinations might be very synergistic, and the subject of some of the next clinical trials. Now that the two Mab's are approved, one of the next steps is to work out optimal combinations, using the Mab's with Novel agents, for different situations (high risk/standard risk, ND or relapse, etc.). Lastly, I have read that so far, it is felt that Mab's have side effects that are of relatively short duration, and not accumulative. Accordingly, the traditional reticence to treat SMM at all may be addressed by use of Mab's, in that there would potentially be little risk of long term adverse effects by the administration of Mab class of drugs in the SMM and MGUS conditions.

I understand that I am dragging this discussion into a level of detail that most might find tedious, but it does look like it is of interest to at least a few of us. Best Regards, JPC