#MMSM #OncTwitter #oncX ⚡️Join me & my colleague @jmikhaelmd 🧵Explore efficacy of quad tx in #NDMM 🔬PERSEUS, GMMG-HD7 & CONCEPT, CEPHEUS, IMROZ, ADVANCE, MIDAS +++ 🆓#CME 👉🏼 bonumce.short.gy/NDMM-TW1-CM… Supported by an edu grant from @JNJInnovMed 📍First, what's your specialty?

2/ Before we jump in, a few disclosures & important links🔗 1️⃣📖#CME info bonumce.short.gy/NDMM-TW1-CM… 2️⃣Take the pre-survey👉bonumce.short.gy/NDMM-TW1-Pr… 3️⃣Get the latest NDMM quad tx efficacy data w/ 🧵👇 4️⃣🏆Claim🆓CME bonumce.short.gy/NDMM-TW1-Po… Now, let's get started!

3/ 🥼In your practice, which regimen are you using most often for 1L therapy in pts w/ transplant eligible(TE) #NDMM? ☎️Phoning friends…What do you do? @RahulBanerjeeMD @PlasmaCellPete @SagarLonialMD @DoctorAKrishnan @NoopurRajeMD @End_myeloma @TomBmt133 @HiraSMian @Mohty_EBMT

4/💃Quads are taking center stage in #NDMM Let’s look @ the📈on quad tx PERSEUS ~🔑trial: SQ dara➕VRd➡️↑outcomes in TE pts 👉↑PFS @ 48m 84.3 v 67.7%; HR: 0.42; P<0.001 👉↑MRD- rate 75.2 v 47.5%; P<0.001 👉↑CR rate 87.9 v 70.1%; P<0.001 🎉🆕SOC ~ quad instead of triplet🎉

5/PERSEUS #ASCO25: sustMRD- in pts on quad maint @ median f/u 47.5m ↑ ustMRD- @ ≥24m w DVRd v VRd: 55.8 v 22.6% 👉Pts w ≥12m sustMRD-: ↑ 48m PFS,regardless of tx 👉Only 3.1% progressn @18m w DVRd v 6.8% VRd 🔑DVRd➡️2.5x⬆️≥24m sustMRD- & ½ progressn risk @≤18m tx @mbeksac56

6/🙋🏻What about replacing dara- with isa- in a quad? GMMG-HD7: IsaVRd v VRd induction➡️isa-len v len maintenance in TE NDMM 👉↑ MRD- rate 50% v 36%; p =0.00017 👉IsaVRd had ↓AE rates & ↓d/c rates v RVd 🎉🆕SOC 👉Results➡️addition of IsaVRd as induction regimen for TE #NDMM

7/⚡️GMMG-HD7 #ASCO25 update w/ PFS benefit in all quad recipients ↑CR 43.5% w IsaVRd v 34% w VRd ↑MRD- rate 66.2% w quad v 47.7% w triplet 👉PFS at 3yr benefit: 83% v 75% w/IsaVRd v VRd ↑MRD- regardless of maint v MRD+ (HR 0.61; P=0.002) 🔮Maint w Isa-len v len is on-going

8/🔬Exciting news for #mmsm Quad tx as🆕SOC for #NDMM Current @EHA_Hematology/@EMN_EuMMnet (1st optn) & @NCCN (pref,cat 1) regimens for TE pts w/NDMM: 🎯DaraVRd➡️SCT➡️len maint 🎯IsaVRd SCT➡️len maint 👏to quad as 1L for TE pts👏 …but what about pts who are TIE /SCT-deferred?

9/CEPHEUS compared induction/consolidation w VRd ± daratumumab (D) followed by maintenance in transplant-ineligible (TIE) NDMM 🗳️The DVRd arm demonstrated which of the following outcomes? @AlGarfall @bdermanmd @mvmateos @OcioEnrique #OncTwitter #OncX #Oncology #MedTwitter

10/ CEPHEUS🔑trial in TIE & SCT-deferrd pts DVRd➡️deeper, more durable MRD- rate TIE cohort: 👉Overall MRD- 63.2 v 41.4% 👉SustMRD @ ≥12m 48.7 v 26.3%; P<0.0001 👉CR 81.2 v 61.6%; P<0.0001 👉HR 0.57, 95% CI 0.41-0.79; P=0.0005 ↓D/C rate w quad 🎉DVRd new SOC for TIE NDMM🎉

11/Do results w isa show similar trends? IMROZ🔑trial IsaVRd➡️IsaRd v VRd➡️Rd in TIE pts w NDMM 👉IsaVRd ➡️↓time to MRD-: 14.7 v 32.8m ↑ PFS @ 60m: 63.2 v 45.2%; HR: 0.60; P<0.001 ↑ CR: 74.7% v 64.1%; P=0.01 🎉IMROZ results support IsaVRd as 🆕SOC for TIE #NDMM pts @szusmani

12/BENEFIT eval'd wkly bortezomib (V) in TIE NDMM IsaVRd➡️IsaVR➡️IsaR v IsaRd➡️IsaR➡️IsaR ↑MRD- rate @ 12mo 51% v 21%; OR: 3.88; 95%CI: 2.27-6.62;P<0.0001 18mo 53% v 26%; OR: 3.16; 95%CI: 1.89-5.28;P<0.0001 🔑Wkly V in IsaRd=deep responses Supports IsaVRd as🆕SOC for TIE NDMM

13/🆕SOC for pts w SCT-deferred or TIE #NDMM🎉 NCCN (preferred, cat 1) & EHA-EMN (1st optn) regimens: 🎯DRd ‘til progression; de-escalate prn 🎯DVRd ‘til progression; de-escalate prn (<80 yr old, not frail) 🎯IsaVRd ‘til progression; de-escalate prn (<80 yr old, not frail) #MMSM

14/Unfortunately, pts w high-risk (HR) #NDMM have 👎poorer prognosis & shorter survival rates vs standard-risk Based on results of GMMG-CONCEPT presented at #ASCO2025, which treatment strategy should be used for pts w/ HR NDMM? Key: 🔸MRD- = Treat to MRD- #MMSM #OncTwitter