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Luciano J Costa Profile picture
@End_myeloma
Apr 5, 2022 • 25 tweets • 48 min read • Read on X
@jmikhaelmd @BonumCe @JanssenUS @pfizer 2/ 🎇🆓 AMA PRA Credit 🎇
CME ℹ️ & ref list👉 bit.ly/3DtOjtZ
🗝️ Disclosure info 👇
#BonumCE #MMSM Image
@jmikhaelmd @BonumCe @JanssenUS @pfizer 3/🛫Taking off...
🤔#biomarker definitions
🎯Dx biomarkers distinguish👥w disease &👥 w/o
🔮Prognostic biomarkers forecast likelihood of a clin event, dz progression or recurrence
🔮Predictive biomarkers identify 👥 more likely to experience favorable/unfavorable effect from 💊💉 Image
@jmikhaelmd @BonumCe @JanssenUS @pfizer 4/ 📊 #BonumCE #MMSM

SP is 63 yo/M presents w anemia & bone pain
BMBX shows 70% clonal plasma cells and FISH reveals t(11;14)
MRI shows multifocal bone lesions
sBCMA is 227 ng/mL and SLAMF7 8.3 ng/mL by ELISA

☑️ Which is diagnostic of #multiplemyeloma in SP❓
@jmikhaelmd @BonumCe @JanssenUS @pfizer 5/ ✅If you picked MRI with >1 lesion 🙌!
#MultipleMyeloma-defining biomarker by @IMFmyeloma IMWG 👉 SLiM 🦀

“S”= 60% clonal bone marrow plasma cells
“Li”= 🆓light chain ratio >100%
“M”=MRI w/ >1 lesion
“C”=calcium
“R”=renal insufficiency
“A”=anemia
“B”=bone lesions Image
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 6/ There are many biomarkers 🎯 for diagnostic & prognostic use in #multiplemyeloma
Predictive biomarkers for response to a specified 💉💊 have not been established
☀️Good 📰!
🧑🏻‍🔬 are 🔬 #BCMA as a predictive #biomarker

#BonumCE #MMSM Image
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 7/ ⬆️ sBCMA above median correlated w/ ⬇️ PFS & ⬇️OS in pts w/ #multiplemyleoma
Correlation 🔎 in ND & RRMM
sBCMA maintained independent prognostic value after adjustment for:
✍️renal function
✍️age
✍️serum β2 microglobulin
✍️hemoglobin
✍️bone disease

#BonumCE #MMSM
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 8/ ⬆️ baseline sBCMA in 👥MGUS & SMM are predictive of progres.➡️ #multiplemyeloma
📈 MGUS PFS HR 3.44 for sBCMA ≥77 vs <77ng/mL
📈SMM PFS HR 2.0 for sBCMA ≥128 vs <128ng/mL
✍️Effect of sBCMA on PFS was maintained when adjusting for baseline MGUS or SMM risk

#BonumCE #MMSM
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 9/ Normalization of sBCMA may:
🔮 OS for 👥receiving tx
🔮 a⬆️likelihood of response

👥 who began tx w baseline sBCMA levels in normal range had a ⬆️ PFS & OS relative to 👥 w⬆️ baseline sBCMA
👥 who had ⬆️baseline sBCMA whose sBCMA normalized during tx had ⬆️OS
#BonumCE #MMSM
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 10/ 📊 #BonumCE #MMSM
☑️Which of the following biomarker-treatment pairs is a POTENTIAL predictive #biomarker in #MultipleMyeloma❓
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 11/ ✅If you picked BCMA - belantamab 👏!
High baseline soluble BCMA correlated w reduced belantamab mafodotin minimum drug exposure concentration @ the end of 21-day dosing interval in ppl w #multiplemyeloma

#BonumCE #MMSM Image
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 12/ 📍Other therapies & sBCMA:
🚗Several studies show that response, PFS, & OS after BCMA-directed CAR T-cell tx in MM are not assoc w baseline BCMA levels on tumor cells

🚗Other CAR-T trials show pretreatment BCMA levels have impact on depth or durability of response
#BonumCE
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 13/ 🔎 Discrepancies between 🚗 CAR-T studies may be explained in part by
1️⃣ Differences in assays used to quantify BCMA expression (flow cytometry > sensitive than IHC)
2️⃣ Measurement of membrane-bound BCMA vs. soluble BCMA (sBCMA)

#BonumCE #MMSM
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 14/ 💎Phase 1⃣ study of SQ elranatamab
▶️(investigational #BCMA targeting bispecific antibody)

👉 free soluble BCMA ⬇️ w/ ⬆️ doses
👉& demonstrated sustained ⬇️throughout each dose interval
#BonumCE #MMSM
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 15/ 🤔 sBCMA = prognostic, ≠ predictive
sBCMA 📉 w/ response to BCMA & non-BCMA bispecific abs in R/R #multiplemyeloma
🤔Phase 1 studies → responders have ⬇️ in sBCMA (88%-teclistamab & 98%-talquetamab)
🤔Non-responders have ⬆️ sBCMA (80%-teclistamab & 49%-talquetamab)
#BonumCE
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 16/ 📊 #BonumCE #mmsm

🔊Have your say...

☑️Which best represents your use of sBCMA #biomarker assay❓
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 17/ #BonumCE #mmsm
🎀 Wrap Up Summary 🎀
✍️ Multiple diagnostic & prognostic biomarkers are routinely used
🙅 No predictive biomarkers are #FDA approved
✍️ Accumulating 📉 supports sBCMA as a biomarker
✍️ Guidelines 🙅 do not currently recommend routine testing for sBCMA
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 18/ Thank you 🙏 for joining this #MMSM #tweetorial w me, @jmikhaelmd & @BonumCe
🌟Want your 🆓 CME?🌟
Click here 👉 bit.ly/3tVNwPi ✅

🚨👇Answer our post-test polls!
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 19/ #BonumCE #mmsm

🚨Posttest Q 1️⃣
📊 Which is a #MultipleMyeloma-defining diagnostic biomarker by the IMWG?
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 20/ #BonumCE #mmsm

🚨 Posttest Q 2️⃣
📊 Which biomarker-treatment pairs is a POTENTIAL predictive #biomarker in #MultipleMyeloma?
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 21/ #BonumCE #mmsm

🚨Posttest Q3️⃣
📊 Which best represents your use of sBCMA biomarker assay?
@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma 22/ 💫 U didn't know this was part of a series of #MultipleMyeloma #CME?
Don’t fret #hemonc #OncTwitter 💕
🆓 #CME 🏆 credit
#BonumCE

#MedTweetorial w @jmikhaelmd & @SurbhiSidanaMD

@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma @SurbhiSidanaMD 23/ 🛑 There's MORE! 🛑

#MedTweetorial on MOAs of BCMA-directed therapies in #MultipleMyeloma
w @ninashah33 & @SurbhiSidanaMD

@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma @SurbhiSidanaMD @ninashah33 24/ #BonumCE
Hope you’re not 🥱 tired yet, there’s also 2 broadcasts for #MMSM learning 🎉
1️⃣ Efficacy of BCMA-directed therapies

👇🎥Broadcast on Efficacy of Approved/Emerg #BMCA-dir Tx in #MultipleMyeloma w @jmikhaelmd @ninashah33 @SurbhiSidanaMD

@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma @SurbhiSidanaMD @ninashah33 25/ #BonumCE #mmsm
I promise, we’re almost done!

👇🎥 Broadcast: Anticipating & Managing Toxicity in BMCA-dir Tx #MultipleMyeloma 🎬
w @jmikhaelmd @ninashah33 & me

@jmikhaelmd @BonumCe @JanssenUS @pfizer @IMFmyeloma @SurbhiSidanaMD @ninashah33 26/ Thanks again for joining!
Follow @BonumCe for more 🆓 #CME on Twitter!

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More from @End_myeloma

Luciano J Costa Profile picture
Jun 16
Some considerations on long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial - The Lancet Oncology 1/x thelancet.com/journals/lanon…
1st things 1st: Celebrate! It is not everyday that a drug changes OS in NDMM, particularly for the young TE patients. It only happened once for Len (in CALGB maintenance trial) and once for Bortezomib ( GIMEMA-MMY-3006, 15 years after Bort availability). 2/X Image
Daratumumab reduced the risk of Death by 45%, Bortexomib reduced by 32%, Len ( OS in maintenance)by 38% for this pop. Factually, anti-CD38mAb have the highest know impact in OS. This adds to MAIA and ALCYONE on OS advantage for adding Dara. 3/X @JNJInnovMed #mmsm @MyelomaTeacher
Read 10 tweets
Luciano J Costa Profile picture
Nov 15, 2023
#ASH23 #myeloma Abstracts I find most clinically relevant, no particular order @mtmdphd 1/x
Dara-Vd in t(11;14) RRMM @NBahlis Very impressive efficacy. Kudos for reporting MRD by ITT in a single arm trial. 2/x
ash.confex.com/ash/2023/webpr…
RVD1000 meets D-RVD326 by Nisha Joseph. Impressive RWE for quads 3/x @JKaufmanMD @AjayNookaMD ash.confex.com/ash/2023/webpr…
Read 10 tweets
Luciano J Costa Profile picture
Oct 1, 2023
@Rfonsi1 , brilliant and-depth analysis as always 🙏🏼🙏🏼. I would also highlight CANOVA is a textbook example of informative censoring and its dangers. Censoring should be small, balanced between the arms and not "informed" by trial design. Let's see what happens here 1/X
Large number of censoring in the Pd arm. These are folks that are not dropping off for progression or toxicity, but for other reasons such as MD or patient choice. Consequences? It eats away power (fewer patients left) and arms can no longer be assumed similar 2/X Image
Let's just look at numbers of patients at risk. If events are happening at similar rate, and censoring is random and not informed, number of patients at risk should stay about the same at each point, instead...3/X Image
Read 7 tweets
Luciano J Costa Profile picture
Sep 28, 2023
MASTER trial final results out in @TheLancetHaem Thanks @bdermanmd for the very nice commentary! Of course I find the results COOL! But I find the story behind it is just as nice! 1/X
sciencedirect.com/science/articl…
c2015, moAbs cooking, MRD by NGS gaining steam, I had time, and had very supportive friends/collaborators @Phari @nsc_natalie @myeloma_doc_com @Chhabra_mayo @ravivij . Let's try something bold? Very naive, in retrospect. Glad my friends didn't mind 2/X
We then teamed up and met with potential stake holders at ASH, many interactions of protocol schema. Some doors shut ("too early"), some not (we choose those). Some of the best ideas, including Rx cessation without maintenance, came from Pharma discussions. 3/X
Read 16 tweets

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