Samer Al Hadidi, MD,MS,FACP Profile picture
Feb 21, 2023 6 tweets 3 min read Read on X
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%)
❓How common are cardiac AEs with carfilzomib?

An excellent summary table @andrew02114 👇

Notice also the renal AEs
❓why cardiac toxicity is more common with carfilzomib compared to bortezomib?

Not very clear, maybe related to endothelial damage, or increased PP2A activity and inhibition of AMPKα/autophagy regulatory axes 👇(Efentakis et al Blood 2019)
Another nice summary table of cardiac AEs with carfilzomib 👇 (Waxman et al JAMA Onc 2018)

AEs are imp and need to watch for

End 🧵

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More from @HadidiSamer

May 27
My top 7 #ASCO24 abstracts to watch for #mmsm

Will have more details on those once presented/published- those are initial thoughts that may evolve according to more data

There are more interesting data will highlight during the meeting

@ASCO

🧵
#mmsm #ASCO24
1️⃣ IMROZ: Isa-VRd vs VRd i n transplant-ineligible NDMM pts

➡️
✅ follow-up: 5 years

✅Median PFS Isa-VRd(NR, estimated 7.5 years!!) vs VRd(4.5 years)

🛑 Grade 5 TEAE: 2 times higher with Isa-VRd (11% vs 5.5%) meetings.asco.org/abstracts-pres…
Image
#mmsm #ASCO24
Thoughts on IMROZ

Very important data

✅median PFS: 7.5 yrs(estimated)
✅Grade IV AEs: higher though compare to:

MAIA: Dara-Rd: median F/U <5yrs (shorter median follow up),death related to AEs (10%) in Dara-Rd👇 Image
Read 16 tweets
Mar 16
#mmsm
How to counsel patients about Cilta Cel using the data from
CARTITUDE-4 and FDA ODAC meeting for earlier use

With data of Cilta cel and Ide cel, assuming having access to both for a given patient, I will personally chose Cilta cel (I explained this before)

🧵
In the first ~6 months after we plan to give you Cilta-cel, you have one out of 12 (8%) chances of dying either of progressive disease or adverse event to Cilta cel, this will depend on the bridging therapy we will use and your response to it (planning is important to ⬇️risk)

/1 Image
If you are able to get your Cilta cel, the risk of death in the first 3 months is 5% , most of those deaths (4%) were related to adverse events. Given the study was done in COVID era, some of the deaths were related to that infection so the risk maybe lower nowadays-esp USA

/2 Image
Read 16 tweets
Sep 14, 2023
GRIFFIN trial @TheLancetHaem #mmsm

➡️

✅Phase II trial of Dara-RVd vs. RVd
✅Final analysis after all pts had completed at least 1 year of follow-up after end of study ttt, had died, or withdrew from study participation.

Some learning points

🧵 thelancet.com/journals/lanha…
Image
Primary endpoint of the study

➡️stringent complete response rate by end of post-HSCT consolidation
➡️Very important portion of the study 👇
➡️Assumption is 15% difference between Dara-RVd vs. RVd.

Note that statistical significance can be ascertained for 1ry endpoint Image
Did the study meet the 1ry endpoint?
sCR post transplant
Dara-RVd: 42%
RVd: 32%

Difference of 10% only

This means study didn't meet 1ry endpoint

Now the assumption for power calculation was 35% sCR in RVd group which was actually less in the study so this is not the reason. Image
Read 10 tweets
Aug 30, 2023
Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma | @NEJM #mmsm

➡️

Quick initial look

🧵 www-nejm-org.libproxy.uams.edu/doi/full/10.10…
Image
Mezigdomide was previously known as CC-92480

✅ modulator of E3 ubiquitin ligase complex containing cereblon
✅ binds to cereblon and subsequently induces proteasome-mediated degradation of certain transcription factors➡️ activation of T-cells Image
✅Pts on expansion cohort were triple class refractory👇

🛑Plasmacytoma was 40% (extramedullary soft-tissue only and bone-based plasmacytomas with a measurable soft-tissue component)

✅weekly Dex 40 mg (for pts >=75 yrs 20 mg)
✅phase II dose is 1 mg daily for D1-21/28 days
Image
Image
Read 7 tweets
Aug 11, 2023
#mmsm
Given the approval of talquetamab and AEs specific for this agent, here I provide some counseling tips and maneuvers to help lessen special AEs

✅Dose: 0.8 mg/kg SC every 2 wks: my preferred dosing

✅About 3 out 4 pts had a response per FDA package insert (n=87 pts)

🧵 Image
#mmsm
🛑dysgeusia: unpleasant or altered taste sensation
🛑No Grade III/IV for this condition

G I: Altered taste but no change in diet
G II: Altered taste with change in diet (e.g., oral supplements); noxious or unpleasant taste; loss of taste

Absence of GIII/IV≠don't exist Image
#mmsm

Ageusia means complete loss of taste (18% per package insert)

How to treat?

Nothing definite, some things may help

✅Check zinc deficiency, can replace/supplement
✅Low dose clonazepam (0.5 mg), may help
✅Oral rinse, pilocarpine oral rinse 1 or 2%-esp with dry mouth
Read 11 tweets
May 27, 2023
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

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