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Vincent Rajkumar Profile picture
@VincentRK
Aug 14, 2020 • 9 tweets • 5 min read • Read on X
There are at least 4 possible reasons why some people with COVID have little or no symptoms.

1) A rapid immune response that conquers the virus
2) Pre-existing cross reactive immunity
3) Genetic factors
4) Low viral load at time of infection

We have emerging data for each. 👇
1) Rapid immune response: This paper from Karolinska just out in @CellCellPress shows asymptomatic and mildly symptomatic patients have high SARS CoV-2 specific cytotoxic T cell responses. cell.com/cell/pdf/S0092… Image
2) Cross reactive immunity:

Many studies show presence of cross reactive T cells presumably from prior corona viral infections. They may not prevent COVID but can attenuate the severity of the disease. I think this is one reason India has less mortality. @nramind
3) Genetic factors: Lots to learn. But from ABO group to ACE polymorphisms studies are coming out on genetic susceptibility. An interesting facotr associated with severe disease is TLR-7 mutations on X chromosome: also explains milder disease in women. jamanetwork.com/journals/jama/…
4) Viral dose at exposure. This is NOT the same as viral dose measured in asymptomatic vs symptomatic people. It’s the initial exposure dose that’s almost impossible to measure. But we have circumstantial evidence. @jeremyphoward @DrSidMukherjee @AliNouriPhD @DrEricDing @ASlavitt
Understanding why some people have completely asymptomatic disease and some get life threatening disease is critical. I’m amazed we know so much in such a short time. But this is nothing compared to what we will know in 6 months to a year. @Rfonsi1
I study cancers of the immune system. My job is to kill the cells that help us fight infection. The same cells that make antibodies. To kill them, we have to understand them. And the one think I’ve learnt is that it’s extraordinarily hard to get rid of them: Normal or cancerous.
Which is why I have hope that natural infection or vaccines will be effective. Maybe not in preventing a recurrent infection. But certainly attenuating the disease and making future versions more like regular flu or hopefully milder.
What is happening in India where disease severity and mortality appear much lower, is related to what I have posted as the 4 factors. And the main one I suspect of the 4 to be playing a role in India is cross reactive prior immunity.

See related thread.
@sumanthraman

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More from @VincentRK

Vincent Rajkumar Profile picture
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
Vincent Rajkumar Profile picture
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
Vincent Rajkumar Profile picture
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
Vincent Rajkumar Profile picture
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
Vincent Rajkumar Profile picture
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
Vincent Rajkumar Profile picture
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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