Thomas Eliot Lew

Doc from Melbourne, Australia. Treats patients with blood cancers and researches new therapies. Loves family, immersive theatre and running.

[Thomas Eliot Lew @thomaseliotlew]

10ys of insights from treating pts with #CLL after venetoclax at @PeterMacCC & @TheRMH summarized in this latest review. Our approach to sequencing novel agents, venetoclax re-Rx and cellular therapies. Privilege to work with giants Prof Tam & Seymour

https://t.co/DBxZqOPGxL

[Thomas Eliot Lew @thomaseliotlew]

Great to see this in print!
VenR is active in BTKi (and mostly chemo) exposed CLL, but most pts will develop PD during or shortly after 2y on VEN
Time limited Rx a rarity in this context
Appears comparable to PIRTO
Lots of room for improvement here

@Eddie_Cliff @victorshiyulin

[Blood Advances @BloodAdvances]

Venetoclax-rituximab is active in patients with BTKi-exposed CLL, but durable treatment-free remissions are uncommon
https://t.co/opCo5KWmnT #researchletter #lymphoidneoplasia

[Thomas Eliot Lew @thomaseliotlew]

High calibre company and a fun night indeed!

[Eddie Cliff @Eddie_Cliff]

So great & energising to get a crew of fab young lymphoma investigators together #ASH23 #lymsm

[Thomas Eliot Lew @thomaseliotlew]

Nice data!

We’ve observed similar results in our Australian cohort. VenR achieved responses in cBTKi-exp, but a mPFS of 26m. Worse if p53 abn.

Rx free remission with VenR post cBTKi is uncommon, and outcomes are modest

Very different from chemo only exp pts as in MURANO

[Mazyar Shadman, MD MPH @mshadman]

Dr. Samples (@LauraSamplesMD) will present her second poster today.

Outcome of pts with #CLL who received venetoclax after failure of cBTKi. @fredhutch data.

A very relevant clinical question.

https://t.co/iGZQJwXd6Y

#ASH23

[Thomas Eliot Lew @thomaseliotlew]

Cohen BRUIN #ASH23 #lymsm
PIRTO for MCL with prior BTKi
N=152, high risk
Median LOT=3
30/60 (50%) TP53mut
ORR 49% CRR 16%
mPFS <6 months, still poor in TP53 unmut group

Bit of a contrast to CLL, PIRTO really quite disappointing in this setting IMO

[Thomas Eliot Lew @thomaseliotlew]

Ribrag #ASH23
MCL >60 or auto ineligible 1L
Randomisation 1: RCHOP v RCHOP/RHAD – no PFS difference
Randomisation 2: Len-R v R as maintenance – PFS better, no OS difference
R2 definitely more toxic, infections & 2nd malignancies

Seems clear to me – don’t add LEN to maintenance!

[Thomas Eliot Lew @thomaseliotlew]

Going to be wild! Can’t wait

#ASH23

[Jamie Kuzich @JantonKay]

Looking forward to presenting our recent work from @TheDawsonLab at #ASH23 this afternoon!

We use SPLINTR linage tracing to understand the clonal and transcriptional dynamics of the rare clones that contribute to B-ALL relapse after CAR-T

https://t.co/R2cCvWdpjj

[Thomas Eliot Lew @thomaseliotlew]

Kumar #ASH23 – impressive work
BOVen (ZANU, Obin, VEN) for TP53mut MCL 1L
N=25
Tox profile looks good - G3+ neutropenia 12%, G1 diarrhea common
ORR 96% CRR 88%
2yPFS 72% 2yOS
Frequent uMRD

The best outcomes ever achieved in this high risk group

[Thomas Eliot Lew @thomaseliotlew]

And nice MRD data from Andy Rawstron
Using I+V, BM uMRD-4 is confidently predicted by:
PB uMRD -5 once
PB uMRD-4 on two recordings 6 months apart

#ASH23

[Thomas Eliot Lew @thomaseliotlew]

Hillmen #ASH23
FCR v MRD I+V 1L fit CLL (Rx 2x time to uMRD)
I+V:
Higher BM uMRD (62% v 40%)
PFS & OS signif better (but driven by IGHVunmut)
More tMN & TRM in FCR

Lots of Qs:
- Who really needs 1L doublet? IMO - not all
- Fixed dur vs MRD driven?
- Will re-Rx work? IMO - yes

[Thomas Eliot Lew @thomaseliotlew]

Hillmen #ASH23
FCR v MRD I+V 1L fit CLL (Rx 2x time to uMRD)
I+V:
Higher BM uMRD (62% v 40%)
PFS & OS signif better (but driven by IGHVunmut)
More tMN & TRM in FCR

Lots of Qs:
- Who really needs 1L doublet? IMO - not all
- Fixed dur vs MRD driven?
- Will re-Rx work? IMO - yes

[Thomas Eliot Lew @thomaseliotlew]

High (and deserved) praise for @drchynchua!

[Chris Hourigan @DrChrisHourigan]

Wow!! As Mark Levis says "the coolest talk he has heard at #ASH23". ⁦@ASH_hematology⁩

[Thomas Eliot Lew @thomaseliotlew]

Too kind Eddie! A terrific session on novel targets in blood cancers

[Eddie Cliff @Eddie_Cliff]

Congrats to the fab @thomaseliotlew for clever translational work & an articulate oral presentation on the role of the mitochondrial E3 ligase MARCH5 and how its depletion leads to synthetic lethality to venetoclax #ASH23

[Thomas Eliot Lew @thomaseliotlew]

Jasani #ASH23
P1 trial: ROR1-CD3 bispecific +/- IBR
Short t1/2, admin via CADD
12 response eval pts
Unclear how high risk they really were
ORR 58%
MRD-4 in 3 CLL/PET CMR 1 MCL
CRS 54%, ICAN 15% (1 G3)

Limited data, admin difficult, CRS & ICANS
Still - deep remissions w/o BCL2i!

[Thomas Eliot Lew @thomaseliotlew]

Woyach #ASH23
P1 trial: LP-168, dual cov & non-cov BTKi
Binds C481S & gatekeeper mut BTK
N=37 CLL (21 C481S, 9 T474)
Bleeding/bruising in 15-30%, all <G3
Infections in 62%, no AF
ORR ~70% at ≥200mg/d (no CR), sim if T474mut
RP2D 200-300mg/daily
No data for L528W… one to watch!

[Thomas Eliot Lew @thomaseliotlew]

Feels like there is a subset of patients that benefit from the CPI+BTKi approach, but how do we identify them or, ideally, build on the regimen to do better?

OS surprisingly good in this cohort despite modest efficacy... makes me wonder if this is a special/selected group

[Ajay Major, MD, MBA @majorajay]

Tislelizumab+zanu in Richter's #ASH23:
- 48 pts, 80% untreated for RT, 35% TP53mut
- 7 possible irAEs (mostly ⬆️LFTs), 3 Gr5 infx
- ORR 58% (CR 19%), mDOR NR
- mPFS 10 mos (only 7 mos in ITT), mOS NR!
Bridging to allo option? PFS still not great. #lymsm #leusm

[Thomas Eliot Lew @thomaseliotlew]

Al-Sawaf #ASH23
P2 trial Tislelizumab + ZANU for ≤2L RT
N=48
ORR/CRR 58.3% / 18.8%
mPFS 10m/1yOS 75%
Well tolerated
Could bridge to allo
Planned protocol amendment to add sonrotoclax coming
Overall modest, but durable responses for some
Now out in Nat Med!

Baby steps for RT...

[Thomas Eliot Lew @thomaseliotlew]

Pretty impressive, particularly for BTKi/VEN exposed pts, for whom outcomes with 2nd target agent usually achieve mPFS ~24m and true time limited Rx uncommon

Is the best place for doublets/triplets as next Rx after 1st targeted agent? May be better than doing this for everyone..

[Ajay Major, MD, MBA @majorajay]

MRD-adapted ven+obi+acala in R/R CLL #ASH23:
- 45 pts, median tx duration 14.7 mos
- 76% uMRD, med time to uMRD ~5 mos
- 94% uMRD even if prior BTK/ven
Interesting time-limited option; optimal sequencing with 1L? #lymsm #leusm

[Thomas Eliot Lew @thomaseliotlew]

Moskowitz #ASH23
Ruxo for RR T-LGL
Seems highly effective in pts with STAT3 mut
Correlative data suggest STAT3mut T cells drive ^ JAK/STAT in the myeloid compartment, and ruxo is acting here to improve disease. V interesting!

Could be a nice option for some tricky cases…

[Thomas Eliot Lew @thomaseliotlew]

Nice (and huge) dataset
Matches a few other series in this space
Incorporation of CPI prior to auto for RR cHL seems to improve outcomes

#ASH23 #lymsm

[Ajay Major, MD, MBA @majorajay]

PD1 before ASCT retrospective #ASH23:
- 981 pts (!!), 20% PD1+/-BV preASCT
- superior PFS if got PD1 (vs BV or chemo alone), also in MV model
- no difference in OS
Huge cohort and I try to give CPI to all R/R cHL prior to ASCT. #lymsm

[Thomas Eliot Lew @thomaseliotlew]

Rutherford #ASH23
Pts ≥60 in S1826 (AVD + BV v Nivo in adv HL)
Nivo:
More neutropenia, hypoT & rash, less sepsis & neuropathy
Lower NRM 4% v 14%
Big EFS improvement (1y 93% v 64%)
1y OS 95% vs 83%, p =0.091

Slam dunk – more effective, better tolerated, new SoC for elderly cHL!

[Thomas Eliot Lew @thomaseliotlew]

Kittai et al #ASH23
RWE for CD19 CART for RT (USA & Aus)
N=69, genetically adverse, 84% VENorBTKi use for RT
Mostly axi-cel 65%, 45% with concur BTKi
mFU 24m, ?plateau around 25-30%
PR - no durability
TRM 27% - toxic!!
Likely lots of unmeasured selection for pts to get here