For those of you interested in multiple myeloma, here is a brief state of the science for treatment.
1/ For newly diagnosed patients, triplets, VRd or DRd, are the standard of care. Current RCTs are examining if we can improve outcome using quadruplets. Eg. PERSEUS trial.
2/ In newly diagnosed myeloma, another question given the cost & potential toxicity of quadruplets is to start with a triplet, and based on MRD status identify patients who need 4 drugs versus this who do equally well with 3 drugs. Eg: EQUATE trial. @myelomaMD@mtmdphd@eaonc
3/ Auto stem cell transplant is still standard of care for eligible patients. Current data indicate overall survival is similar whether the transplant is done early or delayed. But for many reasons we prefer early transplant for most patients.
4/ Lenalidomide maintenance is standard of care after initial therapy. For high risk patients, lenalidomide + bortezomib. Current research questions include whether we can stop maintenance after 2 years, or adjust maintenance based on MRD status. Eg: SWOG trial; OPTIMUM trial
5/ For Relapsed myeloma numerous treatments are being investigated alone and in combination across the world. The more active drug classes we have, the longer the survival. Great progress.
6/ Immunotherapy is the major advance in myeloma. Bispecific antibodies and CAR-T cell therapy hold great promise. Multiple options available for myeloma refractory to lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, isatuximab, alkylators, and transplant.
7/ For smoldering myeloma, we now feel that early therapy is indicated for high risk patients. A comprehensive trial strategy is underway, specifically to see if patients with high risk SMM do better with myeloma like treatment like DRd, or if mild treatment like Rd is enough.
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In the year 2000, a few of us attended an angiogenesis meeting in Boston. We were there to discuss thalidomide
But a side meeting that evening led to trial that went on to get Velcade FDA approved for myeloma. @NEJM
Story in thread.
Velcade (bortezomib) was first introduced to cancer research by the name PS-341.
It was a novel proteasome inhibitor developed by Julian Adams and colleagues a a potential anti cancer agent. @CR_AACR @AACR aacrjournals.org/cancerres/arti…
The ubiquitin-proteasome garbage disposal pathway in cells is a Nobel prize winning discovery.
Proteins that need to be degraded are tagged with ubiquitin tails. Tagged proteins are degraded by the proteasome complex. (This review has details )
The fascinating story of Thalidomide: how this most notorious drug on the planet, banned in the 1960s, made an incredible comeback and revolutionized the treatment of myeloma.
I will also highlight one person whose role is not recognized: Without Dr. Leif Bergsagel there will be no thalidomide for myeloma.
Read on #MedTwitter
The thalidomide story has many takeaways and lessons.
It shows drug development from bedside to bench and back to bedside.
It shows the power and impact of astute clinicians
It shows the power of investigator courage
The role of serendipity
But let’s start at the very beginning.
Thalidomide was synthesized in 1954, and then developed as a sleeping pill by the German company Chemie Grünenthal in the 1950s.
At the time the only sedatives available were barbiturates which had risks of intentional or accidental overdose.
Because thalidomide was felt to be a drug that cannot cause death due to overdose it was marketed as one of the safest sedatives.
By 1961, it was sold in over 40 countries as a sleeping. It was also tragically used to control morning sickness of early pregnancy.
AQUILA trial for high risk smoldering myeloma published in @NEJM today.
@thanosdimop
Personally for me, it is a huge milestone along 25 years of work that started in 1998. #ASH24 #ASH24VR
This story below may help those interested in a clinical trialist career. 1/
In 1998, as a fellow @MayoClinic I was keen to determine if early intervention delayed progression and improved survival in SMM. #ASH24
In 1999, with the help of Tom Witzig, I led a small phase II trial of thalidomide for SMM. @LeukemiaJnl 2/
I was then so fortunate to examine the natural history of SMM, with the legendary Bob Kyle. Honored to be last author on @NEJM paper that also provided data that most progressions occur in the first 5 years of diagnosis.
The start of the concept of high risk vs low risk SMM. 3/