The IMF sponsored a superb multiple myeloma workshop at Mayo Scottsdale. Street cred to Joe Mikhael (Mayo), Jonathan Kaufman (Emory), Keith Stewart (Mayo), Angela Mayo (Mayo), and Kelly Cox from the International Myeloma Foundation. Having just gotten back from EORTC and getting ready for ASH, I was unsure about giving up my Saturday for a patient-centric MM meeting. But I have to say that for those who spend too much time looking through the “mechanism of action” lens it is really eye-opening to listen to some of the best MM investigators actually interact with patients who they obviously care about deeply.
The value of this program is two-fold. For the patients who attended, all of the speakers, but Joe Mikhael in particular, framed some very technical immunotherapy concepts in terms that anybody can understand. And for those who spend their time interpreting the meaning of MM clinical trial data, the partitioning of clinical trial results by treatment stage (induction, consolidation, maintenance, relapse), risk stratification, and transplant eligibility, yielded a great framework for thinking about where new results fit into the existing standards of care.
I’m pretty sure all of these people will freely share the slides that they presented. Reach out, let me know you want them and I’ll beg for you. In the mean time, for the rest of this blog, I am actually going to mention two very upstream chemical entities that have my attention. A little background…
At EORTC one of the key messages was that you can arrest cell cycles all you want, but if you don’t KILL the tumor cells, they’re coming back. So my soap box nowadays, to anybody who will listen, is i’m tired of hearing about multiple hits along a pathway, or a hit on this pathway and then another hit on the feedback pathway. I WANNA SEE SOME TUMOR ASSASSINATION. As Tak Mak said at EORTC, (paraphrased) “Push the cancer cells over the apoptotic cliff”. Simplified, use your pathway inhibitory agent (you pick the tumor, and the “MOA du jour”) to destabilize the tumor enough that the apoptotic can activate irreversible death machinery.
Now, everybody has their favorite apoptotic on the shelf. I just want to mention two of them that got some press at the workshop. The first is dinaciclib, a CKD inhibitor from Merck. Keith showed some results from a Ph-II trial in a patient who had seen bortezomib/dex, then melphalan/prednisone/thalidomide, then Thalidomide, and then blew through lenalidomide/dex. Treatment with dinaciclib monotherapy dramatically reduced tumor burden. It will be informative to see what earlier combination of this apoptotic does.
So the second example: For a guy who professes pacifism, Joe actually had a lot of pretty militaristic analogies. One had to do with whether you would blow up an entire building across the street if that’s where the enemy was, or would it be better to “blow up the back room on the 3rd floor, and spare the rest of the building”. Along the lines of choice #2 is an antibody-drug conjugate from Genentech (see their patent EP2414395) that links FCRH5 (Fc receptor homolog) with a warhead. They did not present any new data on this molecule. I suspect that they’re just being modest (or not pre-disclosing).