Recs for using free light chains (FLC) in practice. #ASH21

1) We get a lot of consults for abnormal FLC ratios /levels. If FLCs are the only abnormality, you don't need to do much unless involved/uninvolved ratio is >8.

Don't chase minor abnormalities.

ashpublications.org/blood/article/…
2/ If there is clinical concern for light chain process like amyloid or if there is intact immunoglobulin M spike, u can do more. But uncomplicated FLC ratio <8 is almost never going to be high risk SMM. #ASH21

Light chain MGUS with FLC ratio <8 is managed like low risk MGUS.
3/ When we first established the normal FLC range it was a new test and the consequences of abnormal value was not known. A very strict cut off was used. We know now that the normal ratio is affected by age and creatinine. @sykristinsson #ASH21 ash.confex.com/ash/2021/webpr…
4/ An abnormal FLC ratio >20 in a patient with smoldering myeloma indicates high risk state if either bone marrow plasma cells >20 or M spike >2. Mayo 20-2-20 criteria. #ASH21

You can fine tune using this scoring system. @mvmateos @BloodCancerJnl nature.com/articles/s4140…
5/ >=10% clonal marrow plasma cells + FLC ratio >100 is used as a myeloma defining event.

But in some, FLC ratio can be markedly elevated due to dimerization of light chains, not excess production. Check urine M protein; if urine levels are very low it's not myeloma. #ASH21

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More from @VincentRK

13 Dec
Besides my Top 5 picks in myeloma at #ASH21 listed below the 3 most important findings being presented in myeloma this year are:

1) A variety of bispecifics showing high single agent activity
2) CAR-T efficacy
3) PFS improvement with Dara-VRd in GRIFFIN

#ASH21VR
Bispecifics and CART single agent activity is more than double of the single agent activity seen with existing drugs. Slide from @TomBmt133 #ASH21 Image
Cilta-cel efficacy presented by @TomBmt133 is also outstanding and well summarized in this tweet by @ninashah33 #ASH21
Read 5 tweets
13 Dec
The same insulin that was sold for $21 in 1996 sells for $275 in 2021.

We must provide relief to patients whose lives depend on insulin, and fix the broken system. @MayoProceedings mayoclinicproceedings.org/article/S0025-…
Only in a broken system can you increase prices like this. Every time your competitor increases price you do on the same day. Because you can. Because there is no completion. Because there is no law that prevents hikes like this on the exact same product. Image
The price hikes succeed because there is a vulnerable population that needs the drug to stay alive and so has to spend whatever it takes. It is government that needs to step in and protect them. @t1international #Insulin4all Image
Read 6 tweets
9 Dec
Reminder: You cannot compare seriousness of Omicron with delta or wild strain by comparing crude rates of hospitalization or deaths

Omicron faces a different, more immune population: half the world is vaccinated and/or had Covid. Millions of vulnerable have died due to COVID.
1/
Vaccination rates are very high in age >65 population. So the most susceptible now are younger & more fit. So Omicron even if intrinsically more serious will appear milder.

Even age adjusted comparisons won't account for pre-existing immunity from prior Covid or vaccination.
2/
Even if omicron causes less serious disease, the high transmissibility is itself a concern because:

a) more rapid spread will cause more people to be affected in a short period of time: A smaller % of a larger number getting very ill will take up hospital & ICU beds
3/
Read 7 tweets
8 Dec
Should Covid vaccines have been 3 doses from the start? Perhaps. But remember it was a miracle we got highly effective vaccines developed, tested, approved & administered within a year of the pandemic.

Science is not magic. We did better than anyone hoped for. I'm thankful.
Science is continuous learning. Science means we are guided by the best research data we have in the moment. Not what we may have in the future.

If we learn something new, or if the virus changes, we adapt.

We now know a booster is better. So we recommend one. Simple as that
So yes, next year we may recommend another booster or a modified variant specific vaccine. We don't know. It depends on what the research shows. Depends on what the risks look like at the time.

That's the way medicine works.
Read 4 tweets
2 Dec
Thread on financial conflict of interest.

1/My 2018 Dollars for Docs: $0

This was enormously difficult & is not sustainable. Coz if you lead trials some small amount gets invariably reported.

$0 is possible only for people who don't lead therapeutic trials. #MedTwitter
2/ I had to go through all kinds of contortions to get to $0, including taking my name off many papers even though I was an investigator. Ride separately from other investigators to meetings. Avoid drinking even bottled water in long meetings to get zero dollars reported.
3/So we have a problem. If you want experts with zero $ conflicts you will end up with people who don't lead clinical trials.

The $ amounts reported do not mean that investigators are enriching themselves: it can be meetings, being authors on papers. Actual cost to do the trial
Read 19 tweets
1 Dec
FDA advisory panel votes in favor of EUA for molnupiravir for treatment of COVID. @Merck

Molnupiravir is a pill taken twice a day for 5 days starting within 5 days from onset of symptoms. @Merck
The main issue with this drug is that in the interim analysis there was a 50% reduction in risk of hospitalization and death. In full analysis the benefit narrowed to 30%.

Is a 30% decrease in risk of severe Covid good enough? Yes in my opinion.
Read 4 tweets

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