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SUMMARY of ASH 2015

| Jack Aiello

Before presenting my ASH summary, I’ll mention a late-breaking abstract presentation that I attended this morning.  Maybe you’ve already heard about CAR-T therapy (Chimeric Antigen Receptor for T-cells).  This very new immunology treatment removes T-cells from the patient and re-engineers and re-infuses them in the patient, so that these CAR-T cells recognize and destroy cancer cells.  It’s been primarily used in ALL patients, but is being tried in other blood cancers (and perhaps solid tumor cancers) more recently.

This very early study looked at 12 multiple myeloma patients who had relapsed and had at least three prior lines of therapy.  These heavily pre-treated patients had T-cells harvested and re-engineered to recognize the B-cell maturation antigen (BCMA) expressed on multiple myeloma (MM)cells (in 60% to70% of MM cases, which was an eligibility requirement for the trial).  Before CAR-T cell infusion, patients were given cytoxin and fludarabine for three days. However, I don’t believe this constituted a stem cell transplant (SCT) typically done before CAR-T therapies.  These patients were then infused with low levels of CAR-T’s to start with and higher levels for subsequent patients.  In all, every patient achieved >= Stable Disease (SD) including one stringent complete response (sCR), one very good partial response (VGPR),  and two partial responses (PRs).  Patients also experienced substantial toxicities (fevers, cytokine release, the need for platelet infusions, and more), but the side effects were all reversible.  That said, in their future trial, CAR-T (BCMA) will only be administered to patients with fewer than 50% plasma cells.  Because the longest a patient is out is only 12 weeks, we don’t know if these responses are durable Still, it’s exciting.

Here’s my preliminary summary of ASH 2015, and I emphasize “preliminary” because I’ll be learning more about the interpretation ASH 2015 results as I listen to follow-up presentations by MM expert oncologists over the next 1-2 months.

  • Smoldering multiple myeloma patients (SMM) that have some indication of high-risk features (e.g. plasma percentage greater than 10% and free light chain ratio greater than 6) should investigate participation in a clinical trial to determine the efficacy of early treatment
  • Three-drug (VELCADE®/Revilmid®/dexamethasone) therapy for newly diagnosed patients has been shown to have longer progression free survival (PFS) and overall survival (OS) than two drugs and should be considered the standard of care.
  • For relapsed patients, treatment isn’t as clear cut but with the approvals of Darzalex (dratumumab), Ninlaro (ixazomib), and Empliciti (elotuzumab), patients have more options as they combine each of these with the baseline Rev-dex. How clinicians will use or “sequence” Dara-Rd, Ixa-Rd, and Elo-Rd will likely be better understood over the next one to two years.
  • Minimum Residual Disease (MRD) testing is not ready for prime time, but it has good prognostic value for MM patients. However, more trials need to integrate MRD so that clinicians can eventually use MRD results to help guide future treatment plans.  And probably, MRD needs to be combined with PET-CT to get the complete picture.
  • In the large French/US study comparing early versus late SCT, the French showed a PFS benefit but not three-yr OS benefit (both arms about 83%), probably because trial results aren not mature. However, the French part of the study only uses only one year of maintenance, whereas the US does maintenance until progression.  The US has yet to report data so will maintenance make a difference?  We’ll see.

* And the future? Other drugs, such as more monoclonal antiboidies (mAbs), new drug categories such as checkpoint inhibitors, as well as the aforementioned CAR-T therapies and vaccines, make it appear that the myeloma future is bright.

So the best recommendation I can make is for you are to stay educated and consider participation in clinical trials because that how myeloma treatments are advanced. Wishing all of you the best of success.

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

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