Vincent Rajkumar Profile picture
Feb 15, 2022 12 tweets 6 min read Read on X
How I Treat Myeloma: 2022 Update.

10 slides. Hope it's useful for oncologists and patients. @NorthTxMSG @MyelomaTeacher

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
Here is a summary of active drugs in myeloma and their mechanism of action. #MedTwitter #myelomaVR

Blue font: not yet approved.

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More from @VincentRK

Jun 27
What’s up with Beta 2 microglobulin (B2M) and myeloma?

Why is it the sole non-cytogenetic marker used in the new IMWG high risk definition?

Why does it matter whether the creatinine is high or not?

Thread
1/
Beta 2 microglobulin goes up in myeloma with either increasing tumor burden OR decreasing renal function.

Thus a high beta 2 microglobulin in myeloma is a reflection of high tumor burden or renal failure or both.

We need to distinguish why the B2M is high!
2/
When B2M is high, it confers adverse prognosis, but why it is high determines what you can do about it.

If the B2M is high because of tumor burden our strategy will be different than if it’s high due to renal failure.

3/
Read 7 tweets
May 24
The remarkable story of Velcade.

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. Image
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…Image
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 )

PS-341 was a proteasome inhibitorascopubs.org/doi/10.1200/JC…Image
Read 13 tweets
May 18
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 serendipityImage
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.Image
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. Image
Read 20 tweets
Dec 9, 2024
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/ Image
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/ Image
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/ Image
Read 12 tweets
Dec 9, 2024
Just out: Paradigm changing AQUILA randomized trial in high risk smoldering myeloma #ASH24
@thanosdimop @NEJM

Daratumumab significantly prolongs time to active myeloma and overall survival. Proud to be a lead investigator of this trial

Slides in thread nejm.org/doi/full/10.10…Image
Main Findings

Daratumumab prolongs:
-Time to active myeloma
-Time to CRAB
-PFS2
-Overall Survival

Plus: Low toxicity, no detriment to QOL, & limited duration therapy. #ASH24 #ASH24VR Image
390 patients with high risk SMM randomized. Largest trial in SMM ever conducted.
Limited duration therapy.

Significant improvement in time to progression to active myeloma or death with Dara.

Benefit seen in almost all subgroups. #ASH24 Image
Read 13 tweets
Aug 24, 2024
Why are prescription drug prices are far higher in the US that other developed countries.

I’ll break it down. A full 360.

1/ We don’t negotiate prices at launch of a new drug. Others do. Image
As a result, we spend billions on common drugs that other countries spend a fraction of the price on.

Some drugs we pay 10 or 100 times more!! Image
2) Generic and biosimilar entry, adoption, and utilization is slower in the US, and there are many barriers.

Timely and adequate free market competition is critically important for lowering price. Image
Read 21 tweets

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