BonumCE Malignant Hematology CME

#MMSM #OncTwitter #oncX ⚡️Join me & my colleague @DrKrinaPatel 🧵Explore efficacy of 1L quad tx #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 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 u do?@nsc_natalie @bendermanmd @szusmani @Ccostello7 @Ashley_Rosko1 @AnnaSureda5 @ravivij @hhashmi87 @SurbhiSidanaMD @mvmateos #mmsm

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 ↑ sustMRD- @ ≥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- & ½progressn 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? #mmsm @AjaiChari @dra_v_hungria @docbraunstein @NBahlis @RahulBanerjeeMD @Bethfaiman

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/#MMSM 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

12/BENEFIT eval'd wkly bortezomib (V) in TIE NDMM IsaVRd➡️IsaVR➡️IsaR v IsaRd➡️IsaR➡️IsaR ↑MRD- rate at 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

15/👏if you chose to treat to MRD- & cont maint GMMG-CONCEPT, largest cohort to eval MRD- in TE & TIE HRNDMM IsaKRd inductn & consolidatn➡️IsaKR maint➡️ ↑MRD- rate: 67.7% in TE & 54.2% in TIE Sustained ≥1yr: 62.6% in TE & 46.2% in TIE 🎉IsaKRd➡️↑deep remissions @Mohty_EBMT

16/📣GMMG-CONCEPT ASCO2025 update, TE pts: 73.2% MRD- post-consolidatn; p=1.91x10-13 86.8% MRD- @ any time 58.4% MRD- ≥CR 40.6% retained ≥2yr sust MRD- Med follow-up: 43m(0-90.2m) mPFS: 72.8m 5yr OS: 72% 6yr OS: 69% ⬆️2yr sustMRD-, ⬆️PFS, 69% OS @ 6yr IsaKRd:🆕SOC for HRNDMM

17/ADVANCE🔑trial demonstrating dara+ standard KRd ➡️↑outcomes in NDMM independent of TE ↑MRD- rate: 59% v 36%, adjOR = 2.5; P<0.0007➡️ 2.5x ↑MRD- rate w/DKRd 👉No new safety concerns ❓Impact on EFS, PFS & OS TBD DKRd👉1L for all pts on KRd backbone regardless of TE status

18/ Looking across trials... e.g. 🔬CEPHEUS 🔬IMROZ 🔬GMMG-CONCEPT 🔬ADVANCE… 🥅MRD negativity emerges as benchmark to create a level playing field Across🔬, regimens and now✅FDA approved as a clinical trial endpt as of April ‘25 #MMSM #OncTwitter #OncX #MedTwitter #MedX

19/MIDAS eval’d MRD-guided consolidatn post 1L IsaKRd in TE NDMM Post 1L, no🔼in MRD- rates for all pts Tailoring tx to MRD post 1L may not➡️MRD- If respond to 1L tx may not need tandem SCT to reach MRD-; cont anti-CD38 &PI 🤔High # pts w t(11;14): impact time to MRD- results?

20/🔑1L in TE & TIE for NDMM SUMMARY🔑 🎯Triplet WAS standard approach, but quad is🆕SOC 🎉Quad is preferred 1L for TE NDMM v triplet 🆕SOC: IsaRVd for TIE NDMM🎉 🎯MRD- emerging as a benchmark in🔬 & clin decision making 👏Great news for pts #MMSM NEXT answer Qs & claim #CME👇