With an eye toward #ASH24, what are the big questions we need to answer in #mmsm myeloma and which studies are poised to answer them.
I would love to hear others’ thoughts too! So let’s go! /1 Newly diagnosed MM-
As we move toward classifying patients as quad eligible or not, the question is who still needs frontline ASCT?
Rather than stratifying by baseline risk, is MRD status after induction the best guide?

Trials that may help to answer this:
- MIDAS
- MASTER-2
- ADVANCE

And let’s not forget that CARTITUDE-6 is comparing frontline ASCT vs cilta-cel. Will we soon be talking about who should get frontline CAR T?

What happens when patients with myeloma and sustained MRD negativity choose to discontinue maintenance? We sought to answer this question in our study MRD2STOP, out now in @BloodCancerJnl nature.com/articles/s4140… Briefly, before I go into our findings. The concept for this study originated 7 years ago with our patients. I was a fellow, and the most common question from our deep responding patients was, "What happens if I stop treatment?" We didn't know, of course, so we tried to answer it

Synthesizing latest evidence for quads in myeloma is difficult.
Here is one way I do it...
A young patient (40s) with newly dx'd myeloma w/ t(11;14) starts Dara-VRd. VGPR + 5% PC in marrow after 4 cycles. Collected stem cells #mmsm #mmMRD But they have young kids, a job - transplant is far from the top of the list.

B/c there were no high-risk features, we decided to continue with an additional 4 cycles (8 total) Dara-VRd instead of ASCT.

After 8 cycles, stringent CR ... but MRD by clonoSEQ at 749 cells/million

Latest in mass spectrometry: The Spanish group reported on serial MS post-CAR T.
Main findings:
1) Early BM MRD assessment by NGF may have false negatives due to hemodilution, potentially explaining why NGF negative rates decreased with time.
#mmMRD onlinelibrary.wiley.com/doi/pdf/10.111…
2) Most patients are peripheral blood MS (+) early post-CAR T because of M-protein kinetics + immunoglobulin recycling
3) Concordance between MS and NGF increase with time

To dara or not to as maintenance?
The Cassiopeia trial update is out!
Among Dara-treated patients in induction, Dara maintenance offered some benefit over placebo with 6 years f/u. HR (0.76) is similar to ixazomib vs maintenance (0.72).
But…

doi.org/10.1016/S1470-…
There’s also great MRD data.
After induction/ASCT/consol, MRD<10^-5 was 34%.
Dara maintenance increased this rate to 65% vs 58% with placebo! Not a big difference suggesting a lag from effect of ASCT.
But sustained MRD<10^-6 more favorable w Dara maintenance with time. #mmMRD

Quads take center stage at #ASCO24 with a focus on the transplant-deferred group.
📢Out now in @BloodCancerJnl is our phase 2 experience with extended Dara-KRd without ASCT, regardless of eligibility.
75% sCR and/or MRD < 10^-5.
3-year PFS of 85%
🧵
nature.com/articles/s4140… The schema is simple:
Dara-KRd x 24 cycles (without ASCT) for newly diagnosed myeloma.
K reduced to days 1/2/15/16 with cycle 9.
Primary endpoint: composite of sCR and/or MRD-neg (10^-5) by NGS after C8

Looking forward to the myeloma #mmsm abstracts at #ASCO24. Here is a list of what I'll be paying closest attention to! 🧵 LBA105 (Trudel): DREAMM-8 comparing Bela-Pd vs VPd. We know it's a (+) study and the phase ½ had 24-mos. PFS of 52% with 50% prior anti-CD38.
How many pts received prior anti-CD38 here?
What was the ocular toxicity with this Bela schedule?
And of course, PFS?

Should MRD negativity be accepted as a surrogate endpoint for clinical trials in myeloma?
What should be part of the FDA discussion tomorrow about MRD? #mmsm #mmMRD 🧵 We need to first discuss the role of mrd as a prognostic biomarker. Perhaps the best visualization of this is a meta analysis by @NikhilMunshiMD that showed MRD-neg was a/w improved PFS and OS regardless of dz setting, sens threshold, cytogenetic risk, IMWG response, or timing

As we get closer to #ASH23, I wanted to share another cool abstract (#1982) from @UCCancerCenter

We asked: Can early MRD by NGS status from the PERIPHERAL BLOOD be prognostic for #mmsm?

We looked at samples from pts treated w/ Elo-KRd (published ) /1 jamanetwork.com/journals/jamao…
We had paired IMWG response status and bone marrow MRD by NGS status for many of the patients still in response at the end of 4 cycles.

First, an update on outcomes with EloKRd without ASCT. 48% had high-risk cyto.
With a median f/u of 45 months, the 4-year PFS was 73%.
/2

Sharing work from our group at #ASH23 in #mmsm!
Dara-KRd x 24 cycles (without ASCT) for newly diagnosed myeloma. The schema is simple: 24 cycles of Dara-KRd. K reduced to Days 1/2/15/16 with cycle 9.
Primary endpoint: composite of sCR and/or MRD-neg (10^-5) by NGS after C8 /1

Patients could have stem cells collected on study but this was a transplant-deferred approach. 88% had SCT collected - median 8.26 x 10^6 CD34+/kg!
We measured MRD with clonoSEQ in the bone marrow and by mass spectrometry (EXENT = MALDI, and liquid chromatography) in blood!/2

The final GRIFFIN analysis is out! What (else) is there to say that hasn't been?
📜Reminder: Randomized phase 2 design, Dara-VRd/ASCT/Dara-R vs VRd/ASCT/R.
#⃣n=207
🥇endpoint: sCR after consolidation (1 sided alpha=0.1)
Mid-trial: Dara maintenance moved from q8w-->q4w. Some other key demographic:
- Mostly younger group of patients. 27% > 65 years of age.
- 15% black pts
- 15% had 'classic' high-risk cytogenetics, but 38% if include 1q CNAs. Whether 1q gain should be considered high-risk is a question, but 1q amp undoubtedly should be.

Are you ready for an #ASCO23 myeloma megathread? Here are 10 important abstracts to tune into to learn more (esp. with so little data in the abstract!). Let's go! #mmsm Abstract 8000: Elo-KRd vs. KRd induction showed sig. improvement in MRD-neg rate (50% vs 35%) at end of induction. Long-term f/u + PFS data will be key. Might there be something about Elo and K synergy? Would this allow for using anti-CD38 mAb later? meetings.asco.org/abstracts-pres…

I get asked all the time: Can MRD status guide treatment decision in myeloma?
📜A separate thread dedicated to #ASH22 studies investigating #mmMRD-guided management in myeloma.
I will post lots more about our MRD2STOP study as we get closer to the conference! #mmsm Abstract 992 (@kordeneha1):
The premise: Patients with 3+ years of MRD-neg (flow, 10^-5 to 10^-6) undergo discontinuation of maintenance. Monitored q6mos bone marrow (flow), yearly PET.
n=23
👍Sustained MRD-neg at 12 months: 14/16 (88%)
👍12 month PFS: 94%
ashpublications.org/blood/article/…

So many excellent #ASH22 abstracts to choose from. Sharing my thoughts on 11 important works, with more to come as we get closer to the meeting! In order of abstract number (not merit)...let's go! #mmsm 158: Elrantamab in R/R MM to be presented by @NoopurRajeMD.
☀️27% Black or asian enrollment
☀️ 24% with prior BCMA-dir therapy
👉ORR 64% (38% CR+)
🚨7/13 (54%) ORR w/prior BCMA-dir therapy. This is the important take home!
⏳Duration of response 17 months
ash.confex.com/ash/2022/webpr…

So many great abstracts to peruse for #ASCO20. Some themes: weekly regimens, anti-BCMA therapies, MRD, & high-risk disease. By abstract #, here are 10(ish) #ASCO20 abstracts that stood out to me for their clinical relevance and intrigue. Long thread incoming! #mmsm #ASCO20BD /1 Plenary LBA3: KRd vs. VRd. No data yet until May 28, but this will be relevant no matter what the outcome is! Note that most high-risk patients were not included in this study. Don't think we'll have a final answer on this debate though! meetinglibrary.asco.org/record/186906/… #mmsm #ASCO20BD /2

Exciting to see results of lenalidomide in smoldering myeloma. It’s clear that lenalidomide prolongs time to progression and to symptomatic disease. I will point out reasons why I am not ready to use this regimen for smoldering myeloma. [thread] #mmsm ascopubs.org/doi/full/10.12… 1) Lead time bias. Not surprising that treating pts earlier will delay progression. We are treating them! We have to think beyond progression too!
2) Only 11/90 pts in placebo arm experienced bony disease and 8/90 renal failure at progression. Also we don’t know severity! #mmsm

Elevated PTT is one of my favorite types of consults, but I think there are a few things that every clinician should assess before consulting:
(1) Is the patient on heparin? If yes, there's your answer :)
(2) No, really, is the patient receiving heparin? Hep Lock, etc.
... #MedEd ...An elevated thrombin time might give you the answer.
(3) Send a PTT mixing study! It's easy, and gives you lots of info! The patient's plasma is mixed with normal plasma. If the PTT fully corrects to normal, it's
a factor deficiency. Partial correction = inhibitor. #MedEd