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Ben Derman Profile picture
@bdermanmd
May 20, 2020 • 12 tweets • 10 min read • Read on X
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
#100: Phase I trial of Teclistamab, a bispecific BCMA x CD3 T-cell engager, showed reasonable rates of CRS (56%, all <grade 3). ORR was 38% at doses >38.4 ug/kg. 7/9 (78%) responded at highest dose (2 were CR + MRD-neg at 10^-6). #mmsm #ASCO20BD meetinglibrary.asco.org/record/186864/… /3
#8501: Weekly Selinexor/Vd has superior PFS to Vd (~14 vs 9.5 months, HR 0.7) in R/R MM. #8530 shows weekly SKd w/ORR 72%. These weekly S regimens are a bit more tolerable than prior twice weekly S combos. #mmsm #ASCO20BD meetinglibrary.asco.org/record/186143/…
meetinglibrary.asco.org/record/186179/… /4
#8506: Chaos from the STaMINA trial! Findings from EMN02 and STaMINA have now flip-flopped! EMN02 shows no diff & STaMINA shows PFS benefit for tandem ASCT in high-risk. BUT this was in the as-treated analysis, not intention to treat. #mmsm #ASCO20BD meetinglibrary.asco.org/record/186147/… /5
#8507: VRd +/- Elotuzumab for high-risk myeloma. 103 pts. 7% had PCL. No diff. in median PFS (31 months for Elo/VRd vs. 34 months VRd) or OS (HR 1.28). Is this a reflection of Elo or a prediction for all quadruplets in high-risk disease? #mmsm #ASCO20BD meetinglibrary.asco.org/record/186157/… /6
#8512: Mass Spec in blood vs Next gen flow in marrow on GEM-CESAR trial. Mass Spec identified disease in ~95% of patients who were positive by NGF-MRD. Mass Spec and NGF are complementary for disease detection! #mmsm #ASCO20BD meetinglibrary.asco.org/record/186156/… /7
#8514: 73% of MM pts relapsed after converting from MRD-neg to pos. Loss of MRD-neg preceded relapse by 1 yr. Attaining MRD-neg w/in 6 mos. of diagnosis led to HIGHER relapse rate! What does this mean for MRD as an endpoint 4 induction? #mmsm #ASCO20BD meetinglibrary.asco.org/record/186150/… /8
#8526: Cross-study comparison of CANDOR & MMY1001. Once weekly carfilzomib 70 mg/m2 is similar in efficacy and toxicity to twice weekly carfilzomib 56 mg/m2. Good news in the age of COVID where once weekly infusions has many advantages. #mmsm #ASCO20BD meetinglibrary.asco.org/record/186186/… /9
#8540: Meta-analysis of randomized phase 3 trials evaluating efficacy of Dara in high-risk MM. Shows that Dara led to improved PFS with little heterogeneity. We need a randomized study using dara in high-risk patients! #mmsm #ASCO20BD meetinglibrary.asco.org/record/187638/… /10
#8543: Obesity in multiple myeloma was PROTECTIVE in an analysis of nearly 6K patients on clinical trials. OS HR 0.84 (95% CI 0.75-0.95). This brings up some interesting theories as to why – reserve against sarcopenia/cachexia? #mmsm #ASCO20BD meetinglibrary.asco.org/record/186173/… /11
BONUS: #8513 (disclosure-I am author on study). Mass spec in blood vs NGS in marrow for MRD eval in MM. LC-MS in blood may reach or exceed sensitivity of NGS (10^-5 - 10^-6), and is an excellent prognosticator. More on this next week! meetinglibrary.asco.org/record/186146/… #mmsm #ASCO20BD /12

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More from @bdermanmd

Ben Derman Profile picture
Dec 6
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?Image
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But let’s back up. Is quad therapy with cd38 mAb the future or will it soon become the past?

We don’t know the optimal duration of proteasome inhibition in any setting. Is 4-8 cycles too little? Too much for some? It’s certainly hard to know.

At #ASH24, we are going to hear about MajesTEC-5
- Arm A/1: Tec+Dara-Rd [n=30]
- Arm B: Tec-DaraVRd [n=19]
- Median f/u 2.6 mos, 35/35 MRD<10-5! G3/4 infxn 27%. CRS 65%

We will also hear about early experience with Belamaf-VRd from @szusmani !

In the future, we will have results from MajesTEC-7 comparing Dara-Rd vs Tec-Dara-R vs Tal-Dara-R.

I have concerns that Tal is not an ideal drug in frontline and the SOC is changing such that Dara-Rd is going to be for more frail patients.

BCMA targeting agents in the frontline are likely our future. The question is what other components are needed to balance risk and benefit!

What is clear is that patients with ultra high risk features do not have great options and we need to do better. What is the right sequence of agents upfront to accomplish better outcomes for these patients?!
Read 7 tweets
Ben Derman Profile picture
Oct 9
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…Image
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
Around this time, a very compelling paper from the IFM-2009 team (@PerrotAurore) showed that patients with MRD < 10^-6 after 1 year of maintenance who then went onto observation had a 3-year PFS of 76%. But it was <50% for pts w/ MRD<10^-6 & MRD 10^-5 (+)
doi.org/10.1182/blood-…Image
Read 15 tweets
Ben Derman Profile picture
Aug 23
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 Image
This might not seem like much - it's <1% disease!

But something stuck with me from our experience with extended Dara-KRd in the trial setting - patients with >100 cells/million did not achieve MRD negativity even with aggressive non-transplant therapy.

I advised to go to ASCT
Read 5 tweets
Ben Derman Profile picture
Jun 21
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…
Image
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 Image
4) MS status at 3 months post-CAR T was not (significantly) prognostic with small # of patients analyzed. This makes sense intuitively given M-protein kinetics.
It really depends on how many IgG-secreting myelomas are in data set (n=14 here), given that these are most persistent Image
Read 5 tweets
Ben Derman Profile picture
Jun 15
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-…
Image
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

Image
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I would love to have more granular data on mrd conversion at 10^-6 from post consolidation to year 1 and then year 2.

Let’s compare to PERSEUS. MRD neg rates were higher post consolidation and that seems to have driven the differences later on as well.

Power of Len vs Thal? Image
Read 4 tweets
Ben Derman Profile picture
Jun 1
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 Image
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! Image
Read 10 tweets

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