Discover and read the best of Twitter Threads about #MMsm

Most recents (24)

The OPTIMUM trial just published in @JCO_ASCO is an important step forward for dedicated approaches to truly high-risk disease.

Lets talk about this trial in detail 🧵

ascopubs.org/doi/abs/10.120…

Non-paywalled link:

drive.google.com/file/d/1LkaST7…

#mmsm
So lets first talk philosophically about add-on trials in myeloma.

There is no shortage of trials in myeloma adding active drugs and showing improved PFS or response rate.

Such trials are usually large trials run for regulatory approval.
These trials can over-treat standard risk disease and expose them to unnecessary therapy in intervention arm, and also under-treat high-risk disease in control arms.

(Example- MAJESTEC-7 where teclistamab is being added to dara/len/dex and given indefinitely to older pts 💔)
Read 18 tweets
Flame Cells: These are plasma cells with vermillion-staining glycogen-rich overstuffed fibrils. Although these cytoplasmic features are suggestive of neoplastic plasma cells, can also be found in reactive cells. imagebank.hematology.org/image/3230/fla… #mmsm #myeloma #MedTwitter #USMIRC #MedEd ImageImage
Mott cell is a plasma cell characterized by an accumulation of multiple Russell bodies, globular cytoplasmic inclusions composed of immunoglobulin imagebank.hematology.org/image/61837/mo… #mmsm #myeloma #MedTwitter #MedEd #USMIRC ImageImage
Russell bodies are cytoplasmic inclusions filled with immunoglobulins imagebank.hematology.org/image/4192/rus… #mmsm #myeloma #MedTwitter #MedEd #USMIRC ImageImage
Read 7 tweets
1/ My time-to-tweet interval re: #ASCO23 myeloma abstracts is longer than my time-to-toci with CAR-T, but finally off 🏥 service and excited to tweet about a few #MMsm gems!

My research focuses on ⬇️ AEs, ⬇️ time tox, & improved workflows. Here are a few that stood out to me:
2/ @bhemato et al, CARTITUDE-4 (cilta-cel in #MMsm 1-3 prior lines).

Beyond dramatic PFS benefit, worth 🔨 home that CAR-T "one & done" (visits become ≤1x per month) vs DPd/VPd [even stronger DKd] always ≥1x visit/month.

Time tox advantage to CAR-T!

meetings.asco.org/abstracts-pres… Image
3/ @adamssperling et al, PHE885 rapidly manufactured CAR-T with ⬇️ T-cell exhaustion.

Bridging before #MMsm CAR-T unlikely to ≥PR but likely to worsen cytopenias.

⬇️ vein-to-vein time to ~2 weeks: less bridging, happier bone marrow, happier patients!

meetings.asco.org/abstracts-pres… Image
Read 11 tweets
Cilta-cel for early relapsed myeloma.

A deep dive-thread where we analyze this trial in incredible detail, all the nuances and subtleties.

Critical appraisal in patient/trainee friendly langauge.

Link to paper:

nejm.org/doi/full/10.10…

#mmsm
#ASCO23
Trial was a comparison of cilta-cel to investigators choice of either dara/pom/dex (86.7% of patients received this) or velcade/pom/dex (12.3% of pts).

Authors write this control arm as "highly effective" standard of care therapy. Was it? Image
So unlike the ide-cel study (KARMMA-3), this trial enrolled patients that were not triple refractory (only 15%)- and only 21% of patients were refractory to daratumumab. Only 21% of patients refractory to carfilzomib.

Hence dara or isa + carfilzomib/dex should have been allowed Image
Read 25 tweets
I have been asked several questions about the #ASCO23 abstract:  
Durability of Responses With Biweekly Dosing of Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma Achieving a Clinical Response in the MajesTEC-1 Study (8034), wanted to create a 🧵 for #mmsmtwitter.com/i/web/status/1…
What were the criteria for switching to less frequent dosing schedules?
• In phase 1, patients had the option to switch from weekly to Q2W (every other week) dosing if they had achieved at least a partial response and at least 4 cycles of treatment
• In phase 2, patients had… twitter.com/i/web/status/1…
Given the rapid and deep responses, why did so many patients not switch (41/104 responders) to the less frequent dosing schedule?
• Switching was not mandated, but optional, for any patient who met the response criteria. This, in addition to the requirement for patients to… twitter.com/i/web/status/1…
Read 4 tweets
Are you ready for an #ASCO23 myeloma megathread? Here are 10 important abstracts to tune into to learn more (esp. with so little data in the abstract!). Let's go! #mmsm
Abstract 8000: Elo-KRd vs. KRd induction showed sig. improvement in MRD-neg rate (50% vs 35%) at end of induction. Long-term f/u + PFS data will be key. Might there be something about Elo and K synergy? Would this allow for using anti-CD38 mAb later? meetings.asco.org/abstracts-pres…
Abstract 8002: Teclistamab + talquetamab in RRMM.
➡️63 pts, 33% HR cyto, 78% triple-class refract., 43% extramed. dz.
⏲️14.4 mos f/u
🚨ORR 84% (73% in EMD)
🛟81% CRS (3% G3), 1 ICANS, 2 DLTs
Impressive ORR - what is durability? Better than sequential?
meetings.asco.org/abstracts-pres…
Read 11 tweets
Check out our correspondence for the real world data on the use of ide cel #mmsm @JCO_ASCO @ASCO @UAMSMyeloma @uamscancer

Intent Matters: Real-World Applicability of ide-cel Usage in the United States

➡️ascopubs.org/doi/10.1200/JC…

Led by @rajshekharucms @columbiacancer

🧵
✅Violation of intent to treat principle

🛑17 of 196 (~9%) of patients who did not proceed to CAR T-cell infusion because of either disease progression/death (n = 12) or manufacturing failure (n = 5) were excluded from the final efficacy analysis👇 Image
➡️ It is important to note that excluding pts who progress while waiting for CAR-T will not reflect the actual real world efficacy of CAR-T therapy
🛑We are adding layers of selection bias:
✅intent to manufacture
✅intent to treat
Notice the PFS/OS curves👇 ImageImage
Read 16 tweets
The Top Down Model 💎 #ICT

THIS TRADING MODEL WILL BE THE GREATEST INFLUENCE TO YOUR TRADING..

*if you're new to ict pls check last page* Image
FRAME THIS DRAWING❗️

Look at the charts and see this model EVERY DAY

Take a look at your favorite furus charts, 9/10 times they have this drawn out for you

Now compare YOUR charts and notice how your winners were setup like this

BELOW ARE MORE EXAMPLES WITH REAL CHARTS Image
Example: #1 $ES

15m (HTF) FVG - 1m (LTF) entry ImageImageImage
Read 8 tweets
How I view PFS and OS and discuss it to patients-

Using myeloma as an example with references.

An educational thread!

/1


#mmsm
I explain what PFS is.

PFS is time from start of treatment to either disease progression or death.

I explain how we don’t have great data from trials on how relapse happens, but retrospective data indicates majority of progressions are biochemical.

onlinelibrary.wiley.com/doi/full/10.10…
I describe that for newly diagnosed MM, PFS does not correlate well with OS due to effective salvage therapies.

I mention attrition here as well, but at least in trials despite well-documented attrition, PFS still hasn’t correlated to OS.

onlinelibrary.wiley.com/doi/full/10.11…
Read 16 tweets
To understand how problematic some of smoldering myeloma trials are, look at the primary endpoint of a single arm study that is currently recruiting👇#mmsm
🛑using IMWG response criteria for multiple myeloma in smoldering myeloma is an inaccurate assumption 🧵 Image
➡️What is a response definition per 1ry endpoint?
All of:
1️⃣Disappearance of original monoclonal protein from blood and urine
2️⃣<5% plasma cells in bone marrow
3️⃣No increase in size or number of lytic bone lesions
4️⃣Disappearance of soft tissue plasmacytomas
Number 3️⃣+4️⃣ are criteria that automatically assign patients into multiple myeloma and should not be present in smoldering myeloma to start with = inaccurate

Number 1️⃣+2️⃣ are criteria that are assumed to be important in smoldering myeloma with no supportive evidence=assumption
Read 5 tweets
The correct answer to this question was smoldering myeloma.

Time for an educational 🧵for trainees/health care folks of all specialties about how we diagnose myeloma!

What are CRAB criteria? How is anemia defined? (Key to this Q)

Whats the deal with "SLiM" criteria?

#mmsm
What are CRAB features?

Hypercalcemia
Anemia
Lytic Bone Lesions
Renal Failure

Anemia is defined as a Hb value of 2 g/dL or 20g/L below lowest limit of normal for the lab, or less than 10g/DL (100g/L)

Is there something magical however about a Hb of 10.1 versus 9.9?
This is where we recognize that there is some arbitrariness/clinical decision making involved.

In general, very mild anemia such as this case would not qualify as a CRAB criteria, and this would be referred to as smoldering myeloma.
Read 19 tweets
The carfilzomib (K) versus bortezomib (V) saga for newly diagnosed myeloma.

An educational, historical and philosophical thread.

#mmsm
V was first approved by the FDA in 2004.

K approved in 2013.

As opposed to V, K is an "irreversible" PI- and is much more active against myeloma cell lines compared to V

(note=pre-clinical efficacy is NOT clinical efficacy- melflufen was 50x more potent than melphalan 🧐!) Image
For a me-too drug to be useful it must offer at least one of the following features:

1) It works when original drug stops working
2) It has more "clinical" efficacy (not just againt cell lines) than original drug
3) It is safer/has different adverse events than the original drug
Read 22 tweets
1/ Question for #MMsm hive mind 🙏

For patients with functional high-risk myeloma (e.g., relapse ≤18 mo of 1st-line Tx), any good summary of data for functional high-risk vs high-risk FISH vs both?

Summarizing what I found so far, but I know I must be missing a few studies! Image
2/ In KarMMa-2 Cohort A from #ASH22 by @szusmani @DrKrinaPatel et al, 37 patients with #MMsm enrolled in early ide-cel trial for functional high-risk.

Of n=22 with evaluable FISH (I wish it were a little higher), 45% didn't have any high-risk features.

ashpublications.org/blood/article/… Image
3/ In #ASH21 RWE #MMsm database analysis by @kansagraMD et al, 1719 pts analyzed inc. hypodiploid as high-risk 🐠

Thanks Ankit for this awesome work! Am I analyzing abstract correctly to say that 73% of functional high-risk pts had standard FISH? 🤯

ashpublications.org/blood/article/… Image
Read 4 tweets
I congratulate the team who worked diligently to produce the PANGEA model to predict myeloma risk

This is the first "dynamic" model that assesses risks, and in my opinion is a step forward from existing models.

Some thoughts in 🧵

#mmsm

thelancet.com/journals/lanha…
Firstly, I commend the team for choosing a trainee (@anniencowan ) as a first author. So inspirational. I saw that for the PROMISE study too, @HabibElKhoury was first author).

This is the way 👏
I also admit I am not a statistician, and this was a very technical read. The results and methods are not an easy read for a clinician. I will focus my comments on the clinical aspect of things, because some of the stats in this manuscript are simply over my head.
Read 15 tweets
#mmsm How do I treat smoldering myeloma?

Observation

How do I treat “high risk” smoldering myeloma?

Observation

Why don’t I enroll on most clinical trials of smoldering myeloma?

Because they assume that treatment (active control arm) is beneficial

🧵
In clinic, my consultation for smoldering myeloma takes a long time to go over details.

Patient must have completed comprehensive workup including advanced imaging

I yet to have a patient telling me they want a treatment after discussion

Patients appreciate uncertainty
Since we treat many patients, I see many smoldering myeloma pts who already started ttt because of oncologist thinking they will help pts and that some in the field are pushing hard to make this “standard of care”, which is not

Few observations👇
Read 15 tweets
Why peripheral neuropathy incidence is lower and cardiac toxicity is higher with carfilzomib when compared to bortezomib in multiple myeloma?

#mmsm
🧵
Peripheral neuropathy with proteosome inhibition:

❓likely caused by inhibition of a serine protease that is critical for neuronal cell survival called HtrA2/Omi

✅ carfilzomib has lower levels off-target protease inhibition (including activity at HtrA2/Omi protease)
❓How common is peripheral neuropathy with bortezomib

IV, twice weekly initial dosing: 35% (>=G3 in 13%)>SC,twice weekly: >=G3 in 6%>SC weekly dosing (ex’s👇)

What about carfilzomib?

Initial trial (PX-171-003-A1)- FDA AA with single agent activity~24% (PN >=G3:1%)
Read 6 tweets
The first randomized trial of CAR-T in multiple myeloma.

nejm.org/doi/full/10.10…
Ide-cel versus a choice of five regimens for relapsed multiple myeloma!

Lots to learn and process from this trial- so let us get started with this deep-dive 🧵

#mmsm
What was the intent/purpose of this trial?

This was not necessarily aimed for us to figure out what the best option is for patients with 2-4 prior lines of therapy, but to fulfill regulatory requirements for approval (given prior approval was based on single arm study).
What was the patient population enrolled in this study?

Had to have 2-4 prior lines of therapy.
84% had prior auto
65% triple refractory
6% penta-refractory.

No clear single best standard of care in this population-important to highlight.
Read 23 tweets
My approach to transplant for myeloma (some nuance lost):
Young stnrd-risk who prioritizes PFS: Upfront auto
Young stnrd-risk who doesn't prioritize PFS: Defer
Young high-risk: Upfront auto
Older high-risk: Transplant only if mel200 can be given
Older standard risk: No auto
#mmsm
3 trials and supporting evidence in brief thread:

1)DETERMINATION: PFS benefit, but no OS at 7-8 years of follow-up, despite low cross-over in control arm
nejm.org/doi/full/10.10…
2)IFM-2009: PFS benefit, but no OS benefit at 7-8 years, although high-cross over to transplant in control arm

nejm.org/doi/full/10.10…
Read 8 tweets
Some of my fav myeloma trials relate to steroids and "less is more".

Highlight importance of independent co- operative group trials that can answer these Q's

A brief educational thread for trainees that highlights the past, present and future of steroids in myeloma!

#mmsm
Trial 1 by the ECOG Group:

ncbi.nlm.nih.gov/pmc/articles/P…

Len+high dose dex (40mg for four days of the week) vs len+low dose dex (40mg once a week) for new dx MM

Despite slightly ⬆️response rate-⬆️toxicity and deaths with high-dose dex.

Established that lower dose steroids better!
What else can we learn from this (amongst many lessons)?

⭐️Relying exclusively on response rates in a single arm trial can miss the bigger picture- it takes randomization with a parallel cohort of patients to assess for competing risks such as treatment related mortality!
Read 12 tweets
Bispecific antibodies, infections & myeloma: a 🧵

Myeloma patients are at high risk of infections

An antibody that drags T-cells to attack plasma cells probably impacts immunity - but we don't know for sure yet

ascopubs.org/doi/full/10.12… @JCO_ASCO @ManniMD1 @akesselheim
#mmsm
We compiled infection rates across myeloma bispecific trials, updated to include #ASH22 data

The majority of patients across trials developed infections, w 20-45% developing grade 3 infections & some deaths from infection ⬇️

Note the frequency of neutropenia & hypogam
Of course, in single-arm trials, we cannot know whether these events are caused by the patients' multiply-relapsed myeloma (known to cause significant immunosuppression), previous lines of treatment, or trial drug/s, or the extent to which each factor contributes
Read 8 tweets
I thoroughly recommend this podcast- an excellent overview on MRD in myeloma, regardless of your views on surrogacy.

Great job educating- @rajshekharucms @End_myeloma @AshKishtagari @BloodCancerTalk

#mmsm

tinyurl.com/y3b63nme

2 pearls that were shared by Dr Costa in 🧵
⭐️Trials that enrolled at time of transplant (as opposed to time of diagnosis) such as STAMINA may not be able to enroll those with the most aggressive disease who relapse during induction or die from toxicity during induction.
⭐️ There were indeed patients who progressed on the MASTER trial after receiving DKRD>transplant while being off therapy.

Yet, even in GRIFFIN (DRVD>Auto>DR) some patients progressed while on doublet maintenance.

We cant attribute progression to them not being on treatment.
Read 5 tweets
How much of precision medicine in myeloma is clever marketing, and how much is actual science?

We hear a lot about isatuximab for gain1q and selinexor for del17p!

We unpack all of this in our editorial just published- led by the great hem/onc fellow @OuchveridzeMD

#mmsm

🧵 ImageImageImage
Link to study:
sciencedirect.com/science/articl…

1) We start by describing how myeloma is incredibly heterogenous yet treated in a uniform fashion.

There indeed is ample opportunity to treat myeloma in a personalized fashion based on unique features!
Next, we talk about melflufen.

At a ODAC meeting, the sponsor of melflufen tried to tell us that for elderly patients (who represented a very small subset) of patients on the trial, melflufen was better than pomalidomide.

The FDA brilliant response 👇 Image
Read 12 tweets
Four facts about MGUS that are under-appreciated or under-recognized.

An educational thread with references!

#mmsm

@rajshekharucms @AaronGoodman33 @HadidiSamer @Eddie_Cliff @RahulBanerjeeMD @HemOncFellows @HiraSMian @nihardesai7
1) The risk of MGUS progressing to MM remains fairly constant over time (i.e does not disappear/decrease after an initial time period).

This is different than smoldering myeloma, where highest risk is in first 2 years.

pubmed.ncbi.nlm.nih.gov/11856795/
2) MGUS defined today after exclusion of lytic lesions by advanced imaging and BM biopsy likely has an even lower risk of progression than cohort described by Kyle et al.

As BM biopsy and advanced imaging weren't done routinely in that cohort- some ppl may have had SMM/MM today!
Read 6 tweets
Although a negative trial, the recently published Vorinostat-Len (VR) vs Len (R) analysis of Myeloma XI RCT had some important learning points🧵#mmsm @profghjackson @DrGarethMorgan1
tinyurl.com/ysxu446k
1. Drugs with high symptomatic toxicities are 𝒏𝒐𝒕 good for maintenance therapy. IMO, drugs like selinexor and belantamab mafadotin are perhaps in the same league and unlikely to be successful in maintenance setting. 2x greater risk of Rx discontinuation in Vorinostat arm!!
2. Great to see that number of patients 𝐜𝐞𝐧𝐬𝐨𝐫𝐞𝐝 at each time point provided in K/M curve! PFS, as an endpoint, is prone to differential censoring. Given higher symptomatic toxicity, I would be concerned about⬆️censoring in VR arm, but there wasn't.
Read 9 tweets

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