🚨 hot off the press 🚨
A (perhaps) underestimated aspect of CAR T-cell therapy: non-relapse mortality.
Check out our new meta-analysis on this clinically relevant topic - out today in
@NatureMedicine
!
Let’s take a deeper dive! Start 🧵
Really excited that our paper on oligoclonal expansion of (CAR) T-cells as a potential contributing pathomechanism of severe CAR-T hematotoxicity is finally out in
@BloodJournal
!
Fantastic transatlantic collab with
Young lab
@nih_nhlbi
!
Tweetorial ⬇️
What mechanisms determine resistance to CAR-T therapy and how can we treat relapse in LBCL and Multiple Myeloma?
Check out our new review
@ASTCT_Journal
!
Are all cytopenias after CAR-T created equal?
We explored that question using the phenotypes of post-CAR neutrophil recovery as a blueprint to examine the pathophysiology of hematotoxicity and study its prognostic impact.
Out today
@ScienceAdvances
🎉
Real honor to present our consensus grading and best practice recommendations for immune effector cell-associated hematotoxicity (ICAHT) on behalf of
@EHA_Hematology
and
@TheEBMT
and entire team today at
#EHA23
!
Manuscript out in parallel
@BloodJournal
Happy to present four abstracts at
#ASH22
this year! Let me share our results on markers of CAR-T immunotoxicity and response
1️⃣ we present the HT10 score as a tool to discriminate between early infections and CRS - now externally validated!
Great to see our
@EHA_Hematology
and
@TheEBMT
consensus guidelines article on immune effector cell-associated hematotoxicity out in full print in
@BloodJournal
! 🎉🎉🎉
Very proud of this European team effort!
Can we identify early infections in the setting of CRS after CD19 CAR-T therapy for r/r B-NHL?
Check out our new paper addressing this question out today in
@Hemasphere_EHA
!
Tweetorial 👇
Very much looking forward to exciting CAR-T research at this years
#ASH23
in San Diego.
Come check out our oral presentation applying the
@EHA_Hematology
@TheEBMT
grading for
#ICAHT
across
#lymsm
and
#mmsm
Grateful for the ASH achievement award 🙌
Powerhouse work by
@ErikaKampouri
and
@JoshuaHillMD
outlining risk factors of CMV reactivation after CAR-T 👍
Beware in patients receiving BCMA directed CART and with extended corticosteroid use 👆
#CARTID
Real honor to defend my Habilitation in Experimental Hematology & Oncology today
@LMU_Immutherapy
@LMU_HaemOnk
on the topic of CAR-T side effects & response determinants!
Tremendous journey with many more ups than downs thanks to the mentorship of
@MSubklewe
@BergweltMichael
In a nutshell:
Auto ineligible ≠ CAR-T ineligible.
Results from the Ph 2 ALYCANTE trial out in
@NatureMedicine
today ⬇️
CMR 71%, mPFS 11.8 mo, mOS NR
Gr 3/4 CRS 8.1%, ICANS 14.5%
Congrats to the authors including
@HouotRoch
and
@BachyEmmanuel
!
Introducing Immune Effector Cell-Associated Hematotoxicity, or ICAHT
Check out our joint
@EHA_Hematology
and
@TheEBMT
survey outlining current practice patterns in
@Hemasphere_EHA
below 👇
While the “H” is silent, hematotoxicity is not…
➡️ ICAHT has the highest cumulative incidence of all adverse events after CAR-T
Had a blast writing this
#ASH23
Educational on CAR-T hematologic toxicities w/
@MSubklewe
&
@DrFredLocke
Check it out 👇
Amazing presentation by
@DavidCdSMD
on an important topic: NRM after CAR T-cell therapy.
- 7246 pts
- infections drive NRM across diverse tx settings
- deficiencies in reporting
Great collaboration across multiple institutions:
@DanaFarber
@MSKCancerCenter
@LMU_Uniklinikum
💪
So excited that our paper describing the CAR-HEMATOTOX model for post-CART hematological toxicity is out in
@bloodjournal
! Real labor of love ➡️ big shout-out to
@marisubklewe
and whole
@lmu
immutherapy team! Highlights ➡️ thread
Congratulations to
@TaniaJain11
and
@DrFredLocke
for this interesting How I Treat on managing CAR-T related cytopenias in
@BloodJournal
👇
Loved seeing the phenotypes being mentioned! The Aplastic Phenotype remains a clinical challenge…
Can we predict toxicity and response im patients receiving BCMA CAR-T for r/r multiple myeloma?
Check out our new paper outlining the prognostic utility of the CAR-HEMATOTOX score out in
@BioMedCentral
Journal of Hematology & Oncology
Tweetorial 🧵👇
Excited to share our new paper outlining the rate of hematotoxicity and infections in MCL patients receiving brexu-cel out in
@AjHematology
!
We were also able to validate the use of the CAR-HEMATOTOX for toxicity prediction in this disease indication 👍
Real honor to receive the “Lymphoma Clinical Research”
#pfreundschuhaward
from the
#GLA
for our research delineating risk factors of toxicity and response to CAR-T therapies and developing the CAR-HEMATOTOX model for hematological toxicity!
@LMU_Immutherapy
@GeneCenter_LMU
Ever wonder how body composition impacts treatment outcomes after CAR-T therapy?
Check out our new paper in
@CIR_AACR
in which we leverage CT-based segmentation analyses to examine the prognostic influence of muscle and adipose tissue.
Tweetorial 👇
Great paper by the impressive French DESCAR-T registry outlining causes of NRM after CAR-T out in
@BloodAdvances
➡️ Infections drive NRM after CAR-T
➡️ CAR-HEMATOTOX associated with overall NRM
Congrats to
@BachyEmmanuel
@c_thieblemont
@HouotRoch
!
Important efforts from a multicenter US group to define Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like syndrome (IEC-HS) as a distinct toxicity category of CAR-T, and to harmonize its grading.
Congrats to the authors!
What a winning performance by
@gloria_iacoboni
highlighting that you’d probably choose a high end CAR than a BITEcycle 😉
Proud to call her a great friend :)
#17ICML
Thanks for featuring our work
@majorajay
!
@DavidCdSMD
will be presenting the updated results, now with >7000 CART patients.
Re: lack of reporting of NRM:
0/16 clinical trials reported NRM as the typical cumulative incidence function!
We need to do a better job…
Huge
#ASH23
meta-analysis by
@KRejeski
et al. demonstrating 1) 58% of CAR-T studies don't report NRM, and 2) 48% of CAR-T-associated NRM is caused by infections. Other interesting point: 6% of NRM caused by second cancers?
#lymsm
#mmsm
#celltherapy
Honored to receive an abstract achievement award at
#ASH21
! Come check out our work studying the HT score in the context of infections + outcomes after CD19-CAR-T: thanks go to my mentor
@MSubklewe
and to our fantastic collab partners !
“And still they lead me back
to the long and winding road”
On the way to CAR-T, the road can be perilous and filled with obstacles.
Glad to have been part of this project led by
@VeitBuecklein
Check out the paper ⬇️
Interesting study from the Moffitt group
@MichaelDJain
+
@DrFredLocke
demonstrating that PCV13 vaccination at 3 and/or 6 mo after CD19CART did not induce a specific humoral response. Suggests marginal gain for vac., more systematic studies on vac. needed!
Big thanks to
@ASH_hematology
for the ASH abstract achievement award!
Can’t wait to present several research projects we have been working on
@LMU_Immutherapy
studying determinants of toxicity and response after CAR-T at this years
#ASH2022
🙌🙌
Inspiring presentation from Brian Sworder from
@AshAlizadeh
lab on 360 degree characterization of tumor intrinsic and extrinsic determinants of treatment response to CD19 CART using ct/cfDNA. Can’t wait to read the final paper!
#ASH22
Important paper on PK modelling of flu LD prior to CAR-T by
@MScordoMD
and
@DrMiguelPerales
out in
@BloodAdvances
👇
👉 Suggests there is a therapeutic window for LD with high response and low toxicity
👉 basis for individualized flu dosing?
Great to be a part of the trifecta of recent
@bloodadvances
publications on the subject of stem cell boost for severe CART-related hematotoxicity: check out our multicenter international study below ⬇️
Had the pleasure to speak with
@VJHemOnc
at
#ASH21
about risk-stratifying post-CART infections and clinical outcomes with the CAR-HEMATOTOX:
Check out the abstract ⬇️
Had the pleasure of speaking with
@VJHemOnc
at
#ASH22
about the diagnostic utility of the CAR-HEMATOTOX score for predicting heme-tox, infections and survival in patients receiving brexu-cel for r/r MCL and BCMA CAR-T for r/r multiple myeloma!
Check out the interview 👇
Three phases of
#dgho2022
1) check out Egon Schiele collection
@Leopold_Museum
2) enjoy a mélange at Café Central
3) Present our data on body composition and CAR-T therapy from
@LMU_Immutherapy
@LabTheurich
Good times! Always great to be in Vienna!
We had a fantastic time working on this project studying the impact of bendamustine prior to CD19 CAR-T in r/r LBCL together with the amazing
#bendaqueen
@gloria_iacoboni
!
Great to see the manuscript out in
@JCO_ASCO
🎉
Check out her informative 🧵 below
Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy
@ASCO
Just published! Here a 🧵explaining the journey behind this manuscript
#CART
There are worse cities to have a conference 😉
#SOHOFrance
Quick sunset evening 🏃 along the Seine enjoying the fantastic colors
Thanks for the invite
@HouotRoch
! Looking forward to talk about
#ICAHT
tomorrow 👍
4️⃣ Utility of the CAR-HEMATOTOX in MM pt. receiving BCMA CAR-T:
HT high: more profound and prolonged cytopenias, increased infection rate, inferior PFS/OS, prolonged hospitalization!
Now with updated follow-up and interesting correlative analyses 👍
This paper combines my favorite topics: - alternative splicing (brings me back to fond times in
@Halene_lab
)
- response to immunotherapies in B cell malignancies
Interesting that CAR-T was able to overcome translation deficient splice isoforms of CD20 🤔
"Here, we report the case of a patient with an idiopathic inflammatory myopathy who was successfully treated with CD19 CAR T cells."
Fabian Müller and colleagues provide a new research letter:
Happy to present on behalf of
@LMU_Immutherapy
on the CAR-HEMATOTOX, a risk-stratification score for CAR T-cell related hematotoxicity developed
@LMU_Uniklinikum
! Looking forward to further optimize, validate and bring to bedside!
@MSubklewe
2️⃣ mechanisms of CAR-T heme-tox 👆
a) distinct pathophysiologic differences between biphasic & aplastic neutrophil recovery.
b) biohasic phenotype represented an independent positive prognostic marker for PFS/OS.
- selected for an ASH achievement award
3️⃣ Utility of the CAR-HEMATOTOX in R/R MCL pt. receiving brexu-cel:
⬆️ heme-tox
⬆️ Infections
🛑 inferior PFS/OS
Determined prior to LD, enabling early risk stratification and risk-adapted mngmt strategies ✅
- selected for oral presentation
This has been a huge team effort and there are too many people to thank !
First and foremost I want to thank my exemplary mentor
@MSubklewe
and co project lead !
@i_yakoub_agha
and
@AnnaSureda5
were real drivers of open discourse and master organizers!
Fresh off the press ➡️ CD19 CAR-T for SCNSL out in
@GreenJournal
👆 CNS response reflects systemic response
✅ Comparable NTOX rates
❗️ Beware of potential pseudoprogression
Fantastic collab with my friend
@pkarschnia
!
@LMU_Immutherapy
@MSubklewe
Hot off the press
@Haematologica
❗️Increased visceral fat distribution impacts CRS severity/onset after CD19 CART
Had a blast working on this project with co-lead
@realDavidS91
! Bringing
@LabTheurich
and
@LMU_Immutherapy
labs together :)
Link Below ⬇️
Our mngmt algorithm is severity based
- risk adapted approach for G CSF and anti infective ppx
- important decision point: is patient responsive to G CSF?
- G CSF refractory cases: can consider boost if available (day 14 & gr 3 ICAHT)
- last resort: allo
Details ➡️ publication
If you’re wondering if body comp also impacts toxicity of CD19.CAR-T, check out our previous report
@Haematologica
👇
Increased visceral fat deposits were associated w/ earlier + more severe CRS via IL-6 👍
Had the pleasure of talking to
@HemOncToday
about new applications of the CAR-HEMATOTOX at the EHA/EBMT CAR-T meeting this weekend!
HT high vs low patients 👆
- 40 vs. 8% severe infection rate
- mPFS 3 vs 13 months
Infections = 1️⃣ cause of NRM post-CART !
@LMU_Immutherapy
On my way back to Barcelona. It has been a great 2-day meeting in
#Lille
under the lead of
@MSubklewe
and
@i_yakoub_agha
. Great discussions with other European colleagues in the field of CAR T-cell therapy. Stay tuned for more news pretty soon!
This seems sort of cool.
BAL cfDNA identifies NSCLC w/sens. of 69% and spec. of 100%. Thoughts
@BenWestphalen
?
Has this been done in lymphoma with malignant PE?
@AshAlizadeh
So take home messages:
By moving from unclear definitions and heterogenous practice patterns
➡️to standardized grading and severity based mngmt recs
➡️ this will enable cross-trial comparisons of this important side effect of cell therapies
Humans & T cells alike: Rest reinvigorates. Happy that our work on T-cell exhaustion upon continuous
#bispecifics
is out in
#Blood
. Thank you to my fantastic PhD student
@philipp_nora
and the entire lab of translational immunology
@LMU_Immutherapy
.
For this reason we initiated an EHA/EBMT wide initiative to put together an international expert panel that
-performed an extensive literature review
-met in subgroups multiple times virtually
-deliberated in-person in Lille in March of this year
#workhard
#teamspirit
In my view the overall high NRM rate of 10.4% is concerning for this real-world population
- Infections were the driving force (>70% cause of death)
- Predicting which pt. are at particular risk for infections will be essential…
@JessicaLittleMD
@JoshuaHillMD
@BilalAbidMD
Recruiting >100 MCL CAR-T pt. and 🧐 hematotoxicity and infections in a granular manner wasn’t an easy task, but hopefully it was worth it!
If you want to use the score, find the GLA online calculator below:
With index event analyses we took a retrospective snapshot of laboratory constellations at the time of an infection vs. CRS.
➡️We found significantly elevated serum procalcitonin levels during infection events, which were not observed during CRS
We hypothesized that current grading is highly variable and practice re: G CSF, ppx, boosts is quite heterogenous.
We confirmed this in a worldwide survey of >50 centers and 18 (!) countries published in
@Hemasphere_EHA
Fascinating study by Sascha Haubner et al from
@Michel_Sadelain
group in
@Cancer_Cell
outlining cooperative CAR signaling as a means to minimize antigen escape in AML.
First off, why is hematotoxicity an issue?
- It’s the most common high-grade toxicity of CAR-T (and BsAb as well)
- qualitatively unique and long lasting
- can predispose for severe infections and prevent subsequent therapies
@JoshuaHillMD
@Kwudhikarn
What are the clinical implications?
➡️ routine serum PCT monitoring may be helpful in CAR-T pts.
➡️ the HT10 score highlights the utility of advantage of dynamic risk assessment
➡️ If validated prospectively, the score will enable risk-adapted decisions on antibiotic use.
2️⃣/3️⃣Because one abstract isn’t enough, 🚀
@gloria_iacoboni
couldn’t help it and decided to go back to back:
Post CAR Prognostic Index (PC-PI):
CART efficacy not impaired by prior bispec exposure in lymphoma:
As beautifully put by David Qualls and Caron Jacobson (not on twitter/c?) in the accompanying commentary
@BloodJournal
:
We hope this manuscript provides an early road map for ICAHT, offering standardized approaches and leading to future research…