Friday was the day before the official start of ASH, otherwise known as Symposium Day where organizations like the International Myeloma Foundation (IMF) provide a panel of myeloma (MM) experts to discuss various topics and are typically attended by hundreds of clinicians.
But first, I have two other topics of discussion. I attended a meeting of the IMF's Global Myeloma Alliance, where representatives of advocacy organizations around the world attended in person or by phone. Participating countries included Canada, Israel, UK, Spain, Australia, South Korea, Malaysia and more. The goal of the GMA is to build upon the knowledge that exists within different countries on topics such as drug access and funding, and leverage that expertise in countries that need it.
Also, I just saw a joint press release from the IMF and Onyx (carfilzomib/Kyprolis) announcing a partnership in support of the IMF's Black Swan Research InitiativeÂ®. The goal of BSRIÂ® is to develop better testing (MRD -- minimum residual disease) that can more quickly determine new drug efficacy and possible cures (MRD-Zero).
Next I attended the IMF Symposium, which was moderated by IMF Chairman Dr. Brian Durie and featured myeloma experts Doctors Shaji Kumar and Vincent Rajkumar (Mayo Clinic); Philippe Moreau (France), Jesus San-Miguel (Spain) and Antonio Palumbo (Italy). The format of this meeting attended by nearly 1,000 clinicians from around the world was to look at 5 case studies. For each study, a treatment question was asked, 2 experts presented Pro (Yes) and Con (No) sides, there was discussion, and the audience voted before and after each case study.
Overall, this symposium validated the importance of having a myeloma expert on your side. Beware though, if you have two or more, they may disagree.
What follows are the questions and my takeaways in some detail:
I) Treat High Risk Smoldering Myeloma (HR-SMM)?
First we need to agree on the definition of HR-SMM. M-spike > 5 g/l AND plasma % > 33% is a possibility but there are others. Dr. San-Miguel (Pro) noted that every other cancer, e.g. breast, lung, benefit from early treatment so why not SMM, where the standard of care is "watch and wait"? And a recent Spanish study for HR-SMM (different definition) using Revlimd + dexamethasone showed an improvement of progression free survival (PFS) by about 2 years. Dr. Rajkumar (Con) said HR-SMM is not defined well. We should look at ultra-HR-SMM (with del 17p or t(4:14)) and treat as MM. And for standard risk SMM, watch and wait. Then for the other group of HR-SMM, look at an on-going trial such as E3A06 that compares arms Revlimid-only (no dex) usage versus watch and wait. The audience voted about 37% pro vs 63% con.
II) Early Stem Cell Transplant (SCT) -Yes or No?
Dr. Moreau argued the Yes side, noting various studies. One showed three-year overall survival of 94% (w SCT) versus 78% (w/o SCT). Dr. Kumar argued No, countering that while an SCT can clearly help some patients, we don't know who they are. An SCT should not be mandatory but could be done at relapse. Both agreed that future results from the on-going IFM-DFCI trial comparing early versus late SCT will be valuable. The audience voted about 82% yes and 18% no.
III) Should Melphalan (Mel) be considered for induction treatment?
Dr. San-Miguel (Yes) showed that in a study of Mel-Pred-Rev versus Mel-Pred, the results were nearly the same. So Mel had a bigger influence on treatment response than Rev. While Dr. Palumbo (No) noted that complete response (CR) rates correlate to long-term outcomes and showed there are better alternatives than Mel combinations (e.g. Vel-Mel-Pred) for generating CR's (e.g. Cfz-Rev-dex). The audience voted about 44% yes and 56% no.
IV) Maintenance Therapy...Yes or No?
The audience vote going into this presentation was 71% yes versus 29% no. Dr. Palumbo (Yes) showed trial results for either Rev or Vel maintenance provided a 1-year improvement before the myeloma reappears. Maintenance has also resulted in fewer deaths compared to non-maintenance arms in trials. As he stated, "Maintenance is really continued treatment." And drug-resistant relapse is much less of an issue than clonal MM cells causing relapse. Dr. Rajkumar (No) countered with the fact that "maintenance after an SCT removes the allure of a treatment-free benefit." He also noted that PFS is not the right endpoint and OS benefits are inconsistent. He recommend that high-risk MM pts (del 17 or t(4:14)) benefit from Velcade maintenance; however standard-risk patients who achieve less than a VGPR (Very Good Partial Response) from the SCT should get Rev maintenance for 2 years, while those getting a VGPR or better should not get any maintenance. His arguments changed the minds of the audience, which then voted 45% yes and 55% no.
V) Should new therapies such as carfilzomib (Cfz) or pomolidomide (Pom) be used in the salvage setting - Yes or No?
Before the presentation, the audience voted 60% yes and 40% no. Dr. Kumar (Yes) showed that both Cfz and Pom have had good Overall Response Rates (ORR) in patients refractory to both Rev and Vel. Dr Moreau (No) argued that since the case study had relapsed after 3 years on Rev maintenance after an SCT, that both non-Rev trials as well as a second SCT were viable treatment options. He convinced the audience which changed their vote to 41% yes and 59% no.
That's it. Great session, demonstrating the complexities of myeloma (there really are "multiple" myelomas) and treatment options.
-- Jack Aiello