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

Dec 9
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
Aug 24
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
Jul 8
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.
Read 13 tweets
Jun 25
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/
Read 13 tweets
Jun 1
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
Read 12 tweets
May 31
Just out: Updated mSMART recommendations for treatment of relapsed refractory myeloma. #MedTwitter @MayoMyeloma

1/ CART is now included as an option for second or higher relapse. msmart.org/mm-treatment-g…
2/ Even though CART (cilta-cel) is approved for first relapse we are NOT including it in our main algorithm. Reserved only for special circumstances in this population. We have a long track record with standard triplets, and we are concerned about CART side effects. Image
3/ The current approach for second or higher relapse continues to define 3 specific types of Triple Class refractory. This makes it easier for clinicians to consider options. Image
Read 6 tweets

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