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Day 1 at ASH 2015

| Jack Aiello

Today was a very long but exciting day at ASH.  It began with a 6 am working breakfast of the IMF’s International Myeloma Working Group (IMWG) that consists of nearly 200 myeloma experts from around the world. From 2003-2015, IMWG has produced 22 written Guidelines covering various treatment topics and has 7 more in review: MRD Definition, Renal Failure, High Risk MM, Salvage Transplant, PET Scans, Secondary Primary Malignancies, and Bone Augmentation. Additional topics under consideration are Long-Term Complete Remission (CR), Whole Body Low Dose CT, and Plasma Cell Leukemia (PCL) Prospectives.

The IMWG members discussed four abstracts to be presented later at ASH. I’ll identify each of them with a quick note but explore more after hearing the complete abstract presentation: 1) RVd versus Rd induction therapy (Triplet therapy proves superior); 2) French half of the French/US Determination trial comparing transplant or not (Transplant shows early Progression-Free Survival benefit, but it’s early and US still needs to report, especially considering the Maintenance difference of one year versus until progression); and two other abstracts on VTD versus VCD induction and on Minimum Residual Disease (MRD).

The IMWG meeting had to be cut short in order to attend the 7:30 am oral session on Myeloma Therapy, with the first presentation given by Dr. Brian Durie, the primary investigator on a Phase 3 trial comparing RVd versus Rd induction for newly diagnosed MM patients. Overall Response Rate ORR (82% versus 72%), CR (16% versus 8%) Progression Free Survival PFS (43 versus 30 months) and Median Overall Survival OS (75 versus 64 months) all showed the benefits of triplet therapy over doublet. Clinical Trial presentations followed on ixazomib, daratumumab, and elotuzumab (all approved November 2015 with certain restrictions), and all produced positive safety and efficacy results.

In a session titled “The Path Toward Curing Myeloma” (you do hear that “C” word more these days), Dr. Alberto Orfao (Spain) said that MRD can only be effective if it’s a standard. He noted that PET-CT and MRI measure myeloma outside the bone marrow, while Next Generation Flow (8/10 color) and Next Generation Sequencing measure myeloma inside the bone marrow.

I also found it hopeful to hear more about CAR-T therapy.  Although these were pre-clinical studies, I’m always excited to see continuing research kind this area of immunology…how to make our own immune systems work better.

Finally, I attended an Education Session titled “Multiple Advances in Myeloma.”  Dr. S. Vincent Rajkumar (Mayo) made an interesting point that some smoldering myeloma (SMM) patients are really myeloma patients (they should be treated now) and other SMM patients are MGUS (who only progress to MM 1% per year). We just need good biomarkers to tell which is which, and these might be Plasma% >= 10% plus any one of the following: high-risk cytogenetics (e.g. del 17p, t(4:14), 1q+) or Free Light Chain Ratio 8-100, or something else to be determined. Dr. Thierry Facon (France) noted that there are currently 242 clinical trials involving maintenance (including consolidation and continuous therapy). These typically include combinations of IMiDS and/or proteasome inhibitors as maintenance, but the future might include a vaccine such as the dendritic cell vaccine being testing after a transplant. And Dr. Sagar Lonial (Emory) discussed combination approaches to myeloma. He said that “myeloma is not a single clonal disease but rather myeloma cells have subtle differences, making combination therapy more effective.”  While triplet therapy is today’s recommendation, tomorrow’s might be adding an mAb (daratumumab or elotuzumab) or HDAC inhibitor (panobinostat).

In between talks, I checked out posters (more on posters in my ASH Summary) and attended a lunch sponsored by Celgene, manufacturer of IMIDs and IMF sponsor to help educate patients.   And this evening I attended the IMF’s annual grants award reception.  After listening to some wonderful patient stories, I was encouraged to see young researchers presented with monetary awards to continue their research in areas that will potentially benefit myeloma patients. And it was touching to hear one of the awardees discuss how hearing patient stories is so personally motivating for him.

That’s it for a long day. Wishing you best of health.

Follow Jack on Twitter: @JackMAiello
http://www.sfbayareamyelomasupport.org
San Francisco Bay Multiple Myeloma Support Group
Meeting locations vary throughout the SF Bay

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