Joseph Mikhael MD
jmikhaelmd.bsky.social
Joseph Mikhael MD
@jmikhaelmd.bsky.social
Professor at City of Hope Cancer Center and Chief Medical Officer of the International Myeloma Foundation
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
NDMM ~ Tweetorial #1: Efficacy of Quad Therapies ***Post-Survey & Application for Credit***
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bonumce.short.gy
September 24, 2025 at 12:50 AM
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?
September 24, 2025 at 12:50 AM
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
September 24, 2025 at 12:50 AM
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
September 24, 2025 at 12:47 AM
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
September 24, 2025 at 12:47 AM
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
September 24, 2025 at 12:47 AM
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
September 24, 2025 at 12:45 AM
14/Unfortunately, pts w high-risk (HR) #NDMM have 👎poorer prognosis & shorter survival rates vs standard-risk
September 24, 2025 at 12:45 AM
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
September 24, 2025 at 12:45 AM
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
September 24, 2025 at 12:45 AM
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
September 24, 2025 at 12:42 AM
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🎉
September 24, 2025 at 12:41 AM
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
September 24, 2025 at 12:40 AM
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?
September 24, 2025 at 12:40 AM
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
September 24, 2025 at 12:35 AM
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
September 24, 2025 at 12:35 AM
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
September 24, 2025 at 12:33 AM
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 🎉
September 24, 2025 at 12:31 AM
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
September 24, 2025 at 12:30 AM
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!
September 24, 2025 at 12:30 AM