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