Joseph Mikhael MD

NDMM ~ Tweetorial #1: Efficacy of Quad Therapies ***Post-Survey & Application for Credit*** Take this survey powered by surveymonkey.com. Create your own surveys for free.

21/
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

& Don't forget to claim #CME > bonumce.short.gy/NDMM-TW1-Post

20/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?

19/ Looking across trials... e.g.
🔬CEPHEUS
🔬IMROZ
🔬GMMG-CONCEPT
🔬ADVANCE…

🥅 MRD negativity emerges as benchmark to create a level playing field
Across🔬, regimens, & now✅ FDA approved as clinical trial endpoint April ‘25

18/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

17/📣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

16/👏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

15/ Based on results of GMMG-CONCEPT presented @ #ASCO2025, which treatment strategy should be used for pts w/ HR NDMM?

💬 reply/comment w/ your answer 💬

1️⃣ Initiate allogeneic SCT
2️⃣ Choose IV instead of subQ
3️⃣ Treat to MRD- then d/c tx
4️⃣ Treat to MRD- & cont maintenance

14/Unfortunately, pts w high-risk (HR) #NDMM have 👎poorer prognosis & shorter survival rates vs standard-risk

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

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

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

10/ CEPHEUS🔑 trial in TIE & SCT-deferrd pts
DVRd ➡️ deeper, more durable MRD- rate

TIE cohort:
👉Overall MRD- 63.2 v 41.4%
👉Sustained MRD @ ≥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🎉

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?

💬 REPLY👇

1️⃣ Deep, more durable MRD-
2️⃣ ⬆️MRD- rates. No🔺in PFS
3️⃣ Similar efficacy, ⬆️VTE
4️⃣ ⬆️ D/C rate in DVRd arm

8/🔬Exciting news for #mmsm
Quad tx as🆕SOC for #NDMM

Current EHA-EMN (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?

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)
🔮Maintenance w Isa-len v len is on-going

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

5/ PERSEUS #ASCO25: sustained MRD- in pts on quad maintenance median follow-up of 47.5m

👉 ↑ sustMRD- at ≥24m w DVRd v VRd: 55.8 v 22.6%
👉 Pts w ≥12m sustMRD-: ↑ 48m PFS, regardless of tx
👉 Only 3.1% progression at 18m w DVRd v 6.8% VRd
🔑 DVRd ➡️ 2.5x ⬆️ ≥24m sustMRD- & ½ progression risk at ≤18m tx

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 🎉

3/🥼In your practice, which regimen are you using most often for 1L therapy in pts w/ transplant eligible (TE) #NDMM?

☎️ #MedSky #HemeSky 💬 reply and let us know what you do in your practice?

1️⃣ DVRd quad
2️⃣ IsaVRd quad
3️⃣ DKRd or IsaKRd quad
4️⃣ VRd
5️⃣ other triplet

2/ Before we jump in, a few disclosures & important links🔗

1️⃣📖#CME info bonumce.short.gy/NDMM-TW1-CME
2️⃣Take the pre-survey 👉bonumce.short.gy/NDMM-TW1-Pre
3️⃣Get the latest NDMM quad tx efficacy data w/ 🧵👇
4️⃣🏆Claim🆓CME bonumce.short.gy/NDMM-TW1-Post

Now, let's get started!

#MMSM #MultipleMyeloma
⚡️#MedSky join me & my friend Dr. Krina Patel

In a #CME 🧵exploring efficacy of quad tx in #NDMM
🔬PERSEUS, GMMG-HD7 & CONCEPT, CEPHEUS, IMROZ, ADVANCE, MIDAS +++

🆓 CME from @bonumce.bsky.social
🔗 to CME ℹ️ 👉🏼 bonumce.short.gy/NDMM-TW1-CME
Supported by an edu grant from Janssen