How and why I treat high risk smoldering multiple myeloma (SMM). Thread.
1/ Based on the progression risk curve over time, and genomic analysis, SMM is now considered a heterogenous clinical entity in which 50% of patients have premalignancy and 50% asymptomatic malignancy.
2/ These two groups can be considered as high risk SMM (asymptomatic malignancy) and intermediate/low risk SMM (premalignancy).
We are specifically concerned about high risk SMM, defined as 50% risk of progression to myeloma over 2 years.
3/ Patients with high risk SMM can be identified by the Mayo 2018 criteria: Also called the 20-2-20 criteria.
4/ The Mayo 2018 criteria have been validated by the IMWG.
One third of all patients with SMM have high risk SMM.
5/ The Spanish RCT of Len/dex vs Observation found benefit with early therapy in high risk SMM in terms of time to end organ damage and overall survival. Risk reduction for progression was 90% in the Mayo 20-2-20 high risk group. @mvmateos
6/ A 90% reduction in time to end organ damage was also seen in the @eaonc RCT of Len vs Observation. Only 6 patients have died in this trial: 2 in the Len arm and 4 in the observation arm. It will take many years to comment on OS. @SagarLonialMD
7/ The question of whether high risk SMM is best treated with mild therapy with Len or Len/dex or with a myeloma like triplet regimen is being studied in the ongoing @eaonc trial. @nsc_natalie@mtmdphd@NorthTxMSG
8/ We have 3 types of trials in SMM.
1) The "necessary" trials for regulatory purposes to show something is better than nothing. 2) The strategic trials to improve outcome 3) The trials aiming to cure.
We are doing these in parallel.
9/ Based on what we know so far, I recommend either clinical trials or early therapy with Len or Len/dex for 2 years in newly diagnosed high risk SMM provided such treatment is feasible in a given country.
There are no more RCTs of treatment vs Observation ongoing.
10/ It is extremely hard to do an RCT in this patient population. I have led 4 of these with my colleagues. I don't make recommendations like this without considerable thought on the pros and cons.
11/ If more details are available at diagnosis, the IMWG scoring system provides a better estimate of risk that can be used to risk stratify patients, for counseling, and management. @mvmateos@myelomaMD
12/ If patients with SMM are being observed without treatment, a rise in M protein accompanied by a fall in hemoglobin by >0.5 gms is associated with a high risk of progression. If BMPC is >20%, risk in these patients is 90% at 2 years.
Some have said they prefer clinical trials. I do too. My algorithm is if trials are not available.
Note all clinical trials currently accruing/planned do not have an observation only arm. There will be no further data on OS between treatment vs observation for several years.
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Important to realize that we use steroids like dexamethasone as anticancer drugs (for myeloma) to kill the same cells that make antibodies & help us fight infection.
They are not antivirals. They are anti immune system. They help the COVID virus if given early or inappropriately
When treating the cancer multiple myeloma, we have found that giving high doses of dexamethasone cause more deaths than low doses. More steroids is NOT better. Less is more. @TheLancetOncolthelancet.com/journals/lanon…
Dexamethasone and other steroids will make any kind of fever disappear and make people feel better, but behind the scenes they cause harm when used incorrectly.
We found all kinds of side effects are higher with higher dose of dexamethasone. From blood clots to infections.
Evidence that current vaccines protect against B1.617 variants seen in India. #VaccinesWork
1/ Although 7 fold more resistant to neutralizing antibodies from convalescent or Pfizer/Moderna vaccinated people, ALL vaccinated sera still able to neutralize. biorxiv.org/content/10.110…
2/ UK study: 88% efficacy with Pfizer, & 60% with AZ against symptomatic COVID. This is only slightly lower than original RCTs of these vaccines, & when compared to B.1.1.7. in this study.
3/ Full vaccinated healthcare workers in India seem to be protected from severe COVID and deaths to a high degree. There are definitely some reports of loss of life in fully vaccinated, but I think these are rare. See thread.
Besides vaccination status, the other consideration is viral dose. Healthcare workers are at risk of high viral dose exposures and multiple repeated exposures which puts them at higher risk. The loss of life described below is tragic. Some are very young doctors.
Worth remembering that people who have raised alarm and advocated caution have been more right on COVID.
It has been a hard year trying to project appropriate level of caution and worry, when faced with some who didn't like masks, some who felt it's just the flu, and some who felt we can just let people get herd immunity by natural infection. @dwallacewellsnymag.com/intelligencer/…
I keep thinking of the times I have been wrong. Where I tried to project optimism: cross reactive immunity protecting India, variants unlikely to be more transmissible & lethal, dismissal of importance of neutralizing antibody levels, potential severity of reinfections.
Fix what's in your control: 1) Avoid steroids unless there is hypoxia 2) When indicated, use steroids at right dose and right duration. 3) Check & control blood sugars 4) Avoid antibiotics
There will be hardly anyone who gets mucor without at least one of these 4 factors.
Sure there may be something else going on in addition because we do have a lot people taking steroids and antibiotics for other reasons, and people who have diabetes who hardly ever get mucor.
But it will take time to investigate these additional factors and see if they can be fixed.
If someone is urgently in need of oxygen now, you have to give whatever oxygen is available. No choice. But you could control sugars, and use steroids at right dose for right duration.
I am aware of anecdotes of fully vaccinated people get seriously ill and even die in India. But these are exceptions. Anecdotes don't give you a sense of the denominator. Exceptions will occur based on level of neutralizing antibody response & the vaccine used. See thread.