1/ Risk stratification: This is important both for counseling patients and to decide on treatment options. The more high risk factors, the higher the risk.
2/ Initial therapy. The 3 main choices are VRd, DRd, and Dara-VRd.
I prefer VRd. But the other options are reasonable. Transplant eligible patients need 3-4 cycles, then stem cell collection.
3/ Initial Therapy. For patients not eligible for transplant, results with DRd are outstanding. But it is more expensive and requires prolonged use of a triplet.
4/ Future of Initial Therapy: Many trials are evaluating 3 vs 4 drugs.
Quadruplets may come out on top. But are they needed for everyone? Or can patients MRD- after a triplet do just as well without the 4th drug. This is what we are trying to answer in our current RCT @mtmdphd
5/ Transplant: Auto Transplant is still important. It's role is not in debate. Only the timing. In standard risk patients less than 65-70, early or delayed may be OK. Patient choice matters. Also prefer early transplant in high risk MM.
OS of early vs delayed at 8 years is same.
6/ Maintenance: Lenalidomide for standard risk; Lenalidomide plus Bortezomib for high risk is the current preferred approach.
Our current US cooperative group phase IIIs are looking at adding Dara, or MRD directed escalation or de-escalation.
7/ First Relapse. Thankfully with today's treatment first relapse occurs about 4 years following initial therapy. This will get longer with time.
When relapse occurs a number of options are available. Choice depends on what the patient is refractory to. My approach is below.
8/ Second or higher relapse. Thankfully the first relapse regimen can usually work for a long time. This is also improving.
There are a number of treatment options available for second or higher relapses.
9/ Immunotherapy provides great promise: especially CAR-T and bispecifics. One CAR-T is already approved (ide-cel). One more maybe in a month (cilta-cel).
A number of bispecifics are showing high activity. And unlike CAR-T are "off the shelf". But none are approved yet.
10/ In the future we may pick immunotherapy based on the target antigen. We will face the situation of myeloma refractory to BCMA targeted approaches. So I'm glad Talquetamab and Cevostamab target something besides BCMA.
Link to thread from yesterday on How we treat smoldering multiple myeloma. @SagarLonialMD@mvmateos
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/
FDA approval doesn’t necessarily mean standard of care.
Thread.
1/
For example FDA approved Dara VMP for frontline therapy in myeloma in 2018.
Literally no one used the regimen in the US.
Literally no one felt the regimen was standard of care in the US.
Before or after approval!
Why?
FDA adjudicates a sponsors submission on whether a given drug/regimen has met the burden of proving safety and efficacy.
Standard of care in clinical practice is a different standard: judgment of risk/benefit of available alternatives, and assessment of trial design/end points.
Cure is a simple word. But there is confusion when it comes to cancer. What cure is in cancer, and what we should aspire for?
When can we say that a given type of cancer is curable?
Thread
1/
There is a difference between when we can say a particular cancer is a curable type versus whether individual patients with a given cancer can be considered potentially cured.
They are not the same.
2/
To call a cancer curable we must be able to treat the cancer for a finite duration, stop all therapy, and know that a certain % of patients will never relapse
Early stage solid tumors, Hodgkin lymphoma, DLBCL, ALL, AML are curable. Real cure. The definition of curable cancer
3/
The 4 big myeloma randomized trials to watch out for @ASCO #ASCO24
1. Isa-VRd vs Isa-Rd newly diagnosed
2.Isa-VRd vs VRd (IMROZ)
3.DREAMM8 Bela-Pd vs Pd
4.Ven Dex vs Pom Dex (Canova)
See thread for why they are important.
1) The Triplet vs Quad trials with will define role of quads in elderly patients with newly diagnosed myeloma. They also provide frontline phase III data with Isatuximab— and a choice between Dara and Isa. For some patients Isa will be more cost effective. @Myeloma_Doc #ASCO24
2) Belantamab will make a comeback.
Corneal toxicity is low with reduced frequency dosing. The drug works very well. And in many patients with refractory myeloma belantamab may be safer and easier to do than bispecifics. We need options. #ASCO24