My takeaways from RedirecTT-1 (tal/tec dual bsAbs in myeloma #MMsm) for @fredhutch journal watch.

[Images but technically no memes in my talk 😉]

Efficacy & safety profiles are both striking! I can't help but wonder what earlier IVIG and bsAb de-escalation might have done.

Also out in @BloodAdvances during #ASH24 by rising 🌟 @nadineabdal and @MayoMyeloma!

PROs strongly correlate with OS in #MMsm. In MVA, fatigue as prognostic for OS as FISH and ASCT 😳

Some confounders (anemia, frailty) but worth studying interventions!

ashpublications.org/bloodadvance...

Out in @bloodjournal during #ASH24 - cool work by @freemanlciaraMD @DrFredLocke et al looking at #MMsm CAR-T in myeloma:

MTV (by PET-CT), sBCMA, BMPC don't always correlate. Some MTV-high but sBCMA-low pts exist - may not respond durably to BCMA CAR-T.

ashpublications.org/blood/articl...

Almost every review I've ever read about myeloma #MMsm starts with something (true) like, "Recent advances in myeloma have led to significant improvements in..."

Quite a jolt to see how different the prognosis was for myeloma 60 years ago... and how these papers used to begin!

With my apologies to toddler parents everywhere…

“Don’t lose it, reuse it!”

Excellent @BloodAdvances work by Goel @MayoMyeloma @VincentRK @myelomaMD et al.

Re-using old myeloma #MMsm drugs can work, esp if years out.

Very relevant to post-CAR-T!

ashpublications.org/bloodadvance...

Excellent open-access #MMsm work in @AjHematology by Zabaleta @BrunoPaiva_UNAV et al!

An important footnote for all the CAR-T vs bsAb efficacy debates: when stratified by MRD status, CAR-T and bsAbs do identically.

Getting to MRD neg is what matters!

onlinelibrary.wiley.com/doi/10.1002/...

11/ #ASH24 Abstract 774 (Manier)

IFM2017-03 trial of Rd vs Dara-R with ø dex after 2 months. Huge PFS, OS, QOL benefits with #downwithdex.

Expected? Yes.

Practice-changing to make "ø dex after 2 cycles" the default control arm in #MMsm? I hope so! 🤞🏻

ash.confex.com/ash/2024/web...

10/ #ASH24 Abstract 773 (Dimopoulos)

🚨 AQUILA trial of dara in high-risk SMM. (Dara way more tolerated than len IMO...)

And I quote:
"60-month OS rates: DARA, 93.0%; active monitoring, 86.9%; HR, 0.52; 95% CI, 0.27-0.98)."

New approval coming soon??

ash.confex.com/ash/2024/web...

9/ #ASH24 Abstract 256 (Cheruvalath)

Preemptive strategy #2 to make BCMA bsAbs safer in #MMsm

Don't wait until IgG < 400 (this is myeloma, not rheumatology)... give IVIG now!

Or even start IVIG right before bsAb starts... both better than waiting!
ash.confex.com/ash/2024/web...

8/ #ASH24 Abstract 932 (Kowalski)

Preemptive strategy #1 to make bsAbs safer in #MMsm...

PPx toci to prevent CRS. n=72, only 14% CRS and only one Gr2 event? Seems better than TEC-1 cohort for sure.

Maybe PPx toci can be cost-effective, after all!

ash.confex.com/ash/2024/web...

7/ #ASH24 Abstract 79 (Gustine)

BUT, are ASCT and CAR-T friends?
Possibly not (I know this is provocative)...

Might high-dose melphalan interfere with T-cell fitness & subsequent #MMsm CAR-T? This might explain PFS discordance between KarMMa-2A and –2B!

ash.confex.com/ash/2024/web...

6/ #ASH24 Abstract 931 (Dhakal)

bsAbs and CAR-T are friends, not foes!
Talquetamab bridging before BCMA CAR-T.

@end_myeloma: "Only place where BCMA must precede GPRC5D is dictionary."

In real life, tal's one of the best #MMsm bridging tools we have!

ash.confex.com/ash/2024/web...

5/ #ASH24 Abstract 366 (Ikeda)

Well, can't we just replace all response assessments with sBCMA?

Maybe! It’s a great predictor of relapses, and WAY better than BMBx/imaging status quo for non-secretory #MMsm.

Now we just need validated assays & cutoffs!

ash.confex.com/ash/2024/web...

3/ #ASH24 Abstract 83 (Claveau)
Q: Well if MRD-P is PD, what isn’t PD in #MMsm?

A: Waiting for a confirmatory set of labs... 98% of the time, single PD timepoint is sufficient.

Asking pt to return for extra labs means more #timetoxicity and no benefit.

ash.confex.com/ash/2024/web...

2/ #ASH24 Abstract 363 (Costa)

Is MRD ⬆️ the new PD in #MMsm?

Great work by @End_myeloma @nsc_natalie et al. "MRD-P" (10x increase in MRD by marrow NGS) basically behaves the same as biochemical PD.

Hard to tame MRD ⬆️ with CD38 triplets once occurs.

ash.confex.com/ash/2024/web...

1/ #ASH24 Choosing my top 10 myeloma abstracts this year was harder than ever!! Kudos to all @ASH_hematology authors for GREAT work 👏

For simplicity, I excluded investigational drugs and focused on:

1️⃣ #MMsm response assessments
2️⃣ Optimizing bsAbs
3️⃣ (Soon) practice-changing

1/ And since we can’t tweet during #IMS24, also worth highlighting CEPHEUS as another LBA!

D-VRd vs VRd in ASCT-ineligible #MMsm - large PFS benefit with CD38 addition even if no ASCT. Love simplicity of the last line: ASCT decision-making should not dictate induction choice!

🚨 AURIGA results in #IMS24 app!

After ASCT in #MMsm, 30-mo PFS 83% Dara-R vs 66% R alone.

Can’t directly extrapolate to quad induction or MRD- after ASCT, and not powered for PFS…

… but as a previously loud cynic of CD38-R maintenance sans RCT data, I am a changed man 🫡