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Monday, December 16, 2013

More on Patient Symposium

One of the interesting presentations at the Patient Symposium (Irene Ghobrial) had to do with considering earlier treatment of Smoldering Multiple Myeloma (SMM) before it develops into full-scale MM.  The current standard of treatment is to do nothing until there is progression to MM.  On the average, SMM has about a 10% chance annual risk of progressing to MM.  However, there is a subset of SMM patients whose risk is much higher.  A clinical risk stratification profile has been established where:
  • bone marrow plasma cells > 10%
  • M-protein > 3 g/dl
  • Free Light Chain Ratio (FLC) <.125 or >8 
Patients with these risk factors have a 50% chance of developing MM within 2 years.  Additional risk factors also indicate a quick progression from SMM to MM, including greater than 60% plasma cells in the bone marrow and t(4;14) cytogenetics.  I can testify to the latter, as I was diagnosed with SMM in May 2011, having both more than 60% plasma cells and t(4;14).  Two months later, when I met Dr. Richardson, it had already progressed to full MM.  Current research is exploring early treatment of SMM patients who exhibit these elevated risk factors.  Early clinical trials have been very promising in preventing these patients from progressing to MM.  More data is needed, but future therapy options are clearly headed in this direction.

Ken Anderson was his usual scintillating self in his presentation, discussing novel MM therapies.  He summarized one of the ASH presentations which demonstrated the overwhelming case for using Revlimid maintenance therapy after stem cell transplant, both in time to progression (TTP) and overall survival (OS).   Yay!  That's me.  He also predicted that because of the effectiveness of the new induction therapies, someday it may not be necessary to do stem cell transplants at all! 

As to future directions, Ken is really excited about the prospects for the monoclonal antibodies.  Trials with daratumumab and elotuzumab have been very promising to date, especially in combination with other drugs.  Also, the oral proteasome inhibitor, MLN-9708 (Ixazomib), that I helped to pioneer during its Phase I trial, is entering Phase III trials and may be on target for FDA approval in the next year or so.  Trial results continue to be excellent.  Because it is an oral drug, Ken feels that one day Ixazomib may become a standard for maintenance therapy.  He is also optimistic about the HDAC inhibitor, ACY-1215, which has shown excellent synergistic results in combination with Velcade, Len, and dex. 

Paul Richardson also gave an excellent presentation.  He reported on the latest ASH stem cell transplant research showing updated results from RVD induction, ASCT,  and RVD consolidation, followed by Rev maintenance.  The results showed that consolidation therapy before maintenance upgraded the response rate by 26%!  That's the path I am on in my ASCT clinical trial.  Obviously, Paul must have known this when I got randomized for the trial, as he told me when I was selected that I was on the best arm of the trial.  I wonder if he had anything to do with my getting selected for this arm.  Hmmm.  In any case, thank you Paul!

Richardson also expounded on the continued proven benefits of carfilzomib (Kyprolis) and pomalidomide (Pomalyst) presented at ASH for relapsed MM, even for those who became refractory to Velcade and/or Revlimid.  This is great news to those of us looking forward to the options that may be available to us when we eventually relapse.  Results with these agents have been so good that future regimens may evolve so that carfilzomib/pomalidomide/dexamethasone (Car/Pom/dex) may someday become the standard front-line treatment for MM.

Paul also presented detailed followup on the latest Ixazomib trials, which continue to show outstanding results.  I'm really happy to have had the privilege of participating in the initial Phase I trials of this amazing drug.  He also presented results bolstering his bias to early ASCT rather than waiting until first relapse.  Finally, he presented excellent recent clinical trial results using the monoclonal antibody daratumumab along with Len and dex in relapsed or refractory MM patients.  The results are very encouraging, suggesting further clinical development.

Sorry for the plethora of technical details in this blog post, but I wanted to do a data dump of what I learned on Saturday before it all faded from my memory and/or I could no longer decipher my cryptic notes.

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