Manni Mohyuddin Profile picture
Dec 24, 2021 8 tweets 5 min read Read on X
I loved all the best of #ASH21 threads this year, but in this thread I highlight 5 deeply flawed marketing advertisements (studies) that should not change practice.
#mmsm 🧵
I will start by saying that it is very hard to criticize studies without offending people, so I apologize sincerely and it is my intention only to call out what I perceive as flawed. I may be wrong, and many of these authors have done more than I ever will for myeloma
1:
bit.ly/3GTkXGt

We had chance to universally give dara upon progression to control arm in newly diagnosed MM in 3 different trials. But we didn’t. And now we shouldn’t just create a modeled scenario with so many assumptions and say it’s better to give dara up front Image
2:
ash.confex.com/ash/2021/webpr…

As a me-too drug offers little advantages over dara, isatuximab could have ran 3 vs 3 trials, or done modeling comparing vs dara with same backbone. But here we get a comparison of dara/len/dex versus isa/carf/dex. Fundamentally diff studies/patients Image
3: ash.confex.com/ash/2021/webpr…

Breaks my heart. You compare people that were fit enough and had better biology to stay on Selinexor for longer to people who couldn’t stay on it for longer. Beyond marketing, what is the scientific value of such an inherently flawed analysis? Image
Study 4:

Cilta-cel is great (for patients with biology stable enough to wait to get therapy).

We don’t need flawed comparisons with patients from different areas of the world, many of whom are getting doublets to know that. What is the value, beyond marketing- of such a study? Image
Study 5:

ash.confex.com/ash/2021/webpr…

No subgroup analysis can salvage a study with a fundamentally unethical control arm.I see efforts made to highlight unique role of seli in del 17p- but remember- it’s compared to doublet that nobody uses, and it’s likely all statistical noise. Image
Again- no offense intended. Not many talk about flaws with such analysis, and I hope we can talk frankly about these issues.
Thank you!
@HadidiSamer @Abdallah81MD @DrPaulyDeSantis @HenryJOncology @Abdallah81MD @VPrasadMDMPH

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More from @ManniMD1

Jul 23
The GEM-CESAR trial of a super aggressive approach to SMM (KRD>Transplant>KR>Len) just got published.

The results are a stunning verdict against early intervention in SMM, despite the way the results are potrayed.

Here is a peer review and critical appraisal of this
#mmsm
🧵Image
This trial enrolled 90 patients.

A third of them (28) of them had what is called myeloma today (SLiM)

As a results, this trial is barely generalizable to the SMM of today.

In fact, many of the ppl who progressed in this trial, actually had MM (as defined today) from the start Image
Read 16 tweets
May 24
The IMROZ trial (Isa-VRd versus VRd for transplant ineligible myeloma) just dropped.

Although the trial is successful, numerous caveats exist.

Six key take-aways regarding this trial, while we await the formal presentation at ASCO



1/

🧵meetings.asco.org/abstracts-pres…
1. The primary endpoint of PFS was met, not reached for Isa-VRd vs 54 mo for VRd

For VRd (without transplant) to get median PFS of 54 months is alot

Context= VRd in ENDURANCE:35 mo and SWOG0777 43 mo PFS

Needs more details, but speaks to fitness/biology of enrolled pts Image
2. We do not have patient characteristics, but I suspect that patients enrolled were actually fit and transplant eligible by US standards.

This is mostly NOT a frail patient population, and will probably be a younger cohort than MAIA trial (median age was 73 for MAIA) Image
Read 7 tweets
May 1
Ten important observations about myeloma and its precursors that I often discuss with patients and teach to trainees in my clinic.

An educational thread

🧵

#mmsm

1/
1) Most, but not all disease progressions at the time of relapse are biochemical (as in myeloma proteins increasing) and not clinical (as in new organ damage, anemia, bone lesions etc)

pubmed.ncbi.nlm.nih.gov/35413102/
2) For those with high-risk disease, remissions appear to be very short without a transplant, and the role of transplant even more important, as shown in this excellent meta-analysis of high-risk disease patients across trials.

pubmed.ncbi.nlm.nih.gov/35377484/
Read 12 tweets
Apr 6
The FDA just approved cilta-cel for early relapse in myeloma (1 prior line of therapy, including PI and IMiD, and refractory to lenalidomide).

My thoughts on the approval of cilta-cel for early relapse in myeloma.

An educational thread:

#mmsm

1/ Image
Good news? Unequivocally so.

There are pts who at only one line of therapy become refractory to multiple classes of drugs.

A study showed that those progressing on or shortly after a quad had a median PFS of 2.5 months with next tx.

Cilta-cel may change disease course! Image
For people who are not refractory to Dara at time of first progression, is this good option?

I do not know. In CARTITUDE-4, only 25% of pts had previous exposure to dara

Cilta-cel had better PFS than dara/pom/dex (which majority of control arm got).

But is it safer/better? Image
Read 17 tweets
Jan 18
Our trial of surveillance incorporating DW-whole body MRI q6 mo for high-risk smoldering myeloma is active.

This is a multi-center effort that aims to define natural history of SMM, and show that close surveillance can prevent morbidity while keeping people off treatment

🧵
Image
Image
This trial involves recruiting 100 patients with high-risk SMM and surveilling closely with q6 month MRI, yearly marrows, and frequent labs.

We aim to show that "morbid" progression events such as fractures, bone lesions and renal injury that doesnt promptly reverse are rare Image
Link:


I sincerely wish to thank the key collaborators who have helped design this study- my dear friend @rajshekharucms over many calls and meetings, @AaronGoodman33 , @rubinstein_md and Dr. Nishi Shah.

And @Eddie_Cliff (I hope to open in
🇦🇺 one day) clinicaltrials.gov/study/NCT06212…
Image
Read 11 tweets
Dec 31, 2023
Inspired by a recent discussion on twitter/X about a trial- here’s a thread about the importance of intent to treat analysis, and the caveats/shortcomings of per-protocol or analysis per “compliance/adherence”.

Buckle yourself up for an educational 🧵
This was a trial of Mediterranean diet in reducing breast cancer recurrence.

We know the Mediterranean diet is good for you- in a rigorous randomized trial, it has actually reduced cardiovascular morbidity.

nejm.org/doi/full/10.10…
But this is a different question altogether- can it reduce breast cancer recurrence?

This trial builds upon some previous large well-done randomized trials that showed zilch effect of dietary interventions in cancer.

Some examples below:
Read 21 tweets

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