Stillwater – January 2017: ASH Highlights

American Society of Hematology (ASH) 2016:
Bev Culy and Barb Davis’s Notes

Smoldering myeloma treatment is still a bit of a mystery as experts don’t want to “overtreat” if the disease is not progressing nor do they want to “undertreat” if the disease is aggressive and quickly evolving into multiple myeloma.   There are a couple of treatment options being tried as well as monthly monitoring to keep tabs on the state of the disease.

•  VRd (Velcade, Revlimid and Dexamethasone)  appears to be the most common and also a very good induction therapy whether the patient proceeds to transplant or not.   Studies show responses exceed that of Revlimid/Dex alone.

Tandem Transplants – A new study shows no long term benefit of having back-to-back stem cell transplants but a single transplant followed by long term maintenance therapy still seems to be the standard of care.

MRD (Minimuum Residual Disease) Testing –  a valuable tool to track the likely long term response in patients.  At this time there perhaps needs to be a large database built following those who test MRD negative to see if those who eventually progress have common characteristics.   Too early to say someone who tested MRD (-) is safe to discontinue treatment as some still do relapse.   Long term patient follow needed.  MRD (-) is most important in high risk patients.  At this time doctors are testing and collecting MRD status but aren’t using to determine treatment.

Darzalex continues to work well for many patients.  Continue to follow what combinations work best for patients who are refractory or high risk.  Becoming the common choice of treatment at first relapse.  Combos are truly validating themselves and being used earlier.

Nelfinavir – an AIDS drug- in combination with Velcade has shown some potentially good trial results (may overcome Velcade resistance)  but with rather severe side effects and toxicities.  Small number of patients on trial – sounds like more trial validation needed before becoming a serious combination.  Other researchers will be looking at similar combinations with these kinds of drugs.

Venetoclax is a promising BCL-2 inhibitor – has shown particularly good results in patients with the T(11:14).  There was an additional trial combining Venetoclax and Velcade which showed some positive results for the larger patient population.  It has had some success with some leukemias and lymphomas.  This is an oral drug and well tolerated without too many neuropathy or hem issues.  This trial is being run by Shaji Kumar at Mayo in Rochester.

Selinexor + dex has been in trials with heavily treated and refractory patients and still has shown some degree of response (around 20%).   There were early challenges with G.I. issues but with aggressive early management most patients can tolerate. This is another oral medication.

CAR-T cell therapy is being tried with 3 different targets:  CD-19, BCMA, or antibody.  Experts say the potential is exciting but not sure if the perfect target has been found yet and also quite concerned about the toxicity of the treatment as it can make patients very very ill.  Advise to use caution before considering.

Joe Mikhael of Mayo Clinic top ASH Points:
1. Fewer if any tandem transplants.
2. Darzalex Combos are truly validating themselves and being used earlier
3. Selinexor and Venetoclex need to get approval sooner rather than later
4. CAR-T therapy close but not for sure if yet ready for everyone

Dr. Sagar Lonial, Emory University top point:
Target and Enhance immune function against MM

Links to IMF online videos:
ASH 2016: IMWG Conference Series: Making Sense of Treament
ASH 2016: New agents/combos

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