Nosha Farhadfar updates us on ongoing Ph1 multicenter study of SENTI-202, a first-in-class, CD33 and/or FLT3 & not endomucin, selective off-the-shelf logic gated CAR NK cell therapy in 20 adults w/ R/R AML/MDS w/ FLT3 and/or CD33, max 3 prior tx (max 2 for MDS IB). No DLTs seen. (1/2) #ASH25.

Peihua Lu back to the podium to discuss CTD402 (being developed in US by Imviva), a CD7-targeted CAR T-cell product for R/R T-ALL in pediatric/adult pts. Focused on 41 pts in RP2D cohort (400 million cells). 9/41 w/ ETP-ALL, 10/41 w/ prior HCT. 5 pts w/ G3+ CRS; 0 (!) w/ ICANS or HLH. #ASH25 (1/2)

Robert Chiesa of Great Ormond Street presents on allogeneic CD7-targeted "base edited" CAR T-cells for R/R T-ALL (gene editing to disrupt TCRab/CD52/CD7). 11 children enrolled (9 treated) +2 adults; one infusion of CD7 CAR T-cells. 3 w/prior HCT. All w/active BM dz at lymphodepletion. (1/2) #ASh25

Dr. Tingting Yang presents on sequential CD7-targeted CAR T-cell therapy followed by HCT without conditioning and GvHD ppx for 19 pts w/ R/R AML or T-ALL/LBL. aGVHD in 59% as below; 17/19 full donor chimerism at 1 month; 11/19 remain alive (10 in CR). Median PFS/OS 12.3/14.6 months. (1/2) #ASH25

Dr. Peihua Lu presents on CD7 CAR T-cell therapy in 30 pediatric and adult pts w/ R/R T-ALL using NS7CAR (natural selected CD7 CAR product w/o gene editing), all with CNS-2/3 involvement. All received bridging. No manufacturing failure. Vein to vein time 2 weeks. (1/2) median#ASH25

Dr. Quynh Long Khuong from UPenn presents on possible use of BB/ACEi to reduce cardiotoxicity in pediatric pts w/ AML receiving anthracycline-based induction using multicenter cohort. 908 pts studied; modest but significant reduction in LVEF reduction and mortality w/ BB. (1/2) #ASH25

Zachary Graff of @medicalcollegeofwi.bsky.social presents on CNS disease status in pediatric pts w/ AML treated on AAML1831. CNS-1/2/3 (using ALL definition) status predicted EFS when retrospectively applied to prior COG studies. AAML1831 delayed LP to d8 and used more triple IT tx. (1/2) #ASH25

Dr. Talha Badar from @mayocliniccancer.bsky.social presents on selection of HMA for new-dx TP53m AML. 321 pts (138 aza/183 dec), median age 71, no sig diff in genetic profile. Slightly higher CR/CRi (54 vs 39% w/ dec vs aza). EFS/OS similarly poor. Complex CG assoc w/ worse EFS/OS. (1/2) #ASH25

Dr. Quan Do of VCU Healt Systems presents on risk of heart failure (HF) post-idarubicin vs daunorubicin; structurally, ida expected to be less cardiotoxic, though clinical trials haven't suggested the same. TriNetX database used to assess HF rate w/in 10y of AML tx w/ dauno/ida in 7+3. (1/2) #ASH25

Dr. Montesinos presents on "indolent" AML based on PETHEMA registry data. A subset of pts age ≥60y have longer-term survival (≥9 mon) w/ best supportive care (BSC) alone (192/2506). ↓ WBC/PB+BM blasts/LDH, ↑albumin in indolent AML; PLTs/albumin/BM blasts remained sig in multivar analysis. #ASH25

Dr. Douglas Tremblay from Mount Sinai presents on association of nadir bone marrow aspirate (BMA) characteristics w/ reinduction outcomes based on 233 pts from ECOG-ACRIN AML studies (E1900, E2906). Mostly intermediate/adverse risk. Median 15% reduction w/ reinduction, 52% CR w/ reind. (1/2) #ASH25

Aman Wadhwa presents on risk factors for CNS relapse in 21,830 pts w/ de novo B-ALL across COG studies 2004-2019. Certain risk factors for BM relapse (age, female sex) did NOT predict CNS relapse. Cumulative incidence of CNS relapse 2.2%, median time 24.6 months. (1/2) #ASH25

Thai Hoa Tran from CHU Sainte-Justine in Montreal reports on 196 pediatric/AYA pts (age <25y) w/ T-ALL harboring ABL-class fusions (~5% of T-ALL) from multinational retrospective study within Pointe di Legno consortium. 69% w/ NUP214::ABL1, 8% BCR::ABL1. 72% male. Median dx WBC 83. (1/2) #ASH25

Nicolò Peccatori presents on PAX5r B-ALL in 162 pediatric pts treated on consecutive AIEOP-BFM ALL trials in Italy/Germany/Austria. 60 PAX5 fusion partners seen. Trend toward more IKZF1-plus, ↑WBC and NCI-HR. Analysis of prospectively identified pts (vs controls): no diff in MRD resp (1/2) #ASH25

Sankalp Anora of @mdanderson.bsky.social presents on risk factors for relapse in 213 pts receiving frontline blinatumomab in any phase of treatment. 2y cumulative incidence relapse ~11.4%. Descriptive analysis of factors associated w/ relapse below. (1/2) #ASH25

Sumit Gupta from @sickkidsto.bsky.social presents an update from AALL1731 (previously showed DFS benefit w/ blina + chemo in SR-avg and SR-high in pediatric B-ALL). In pts randomized to blina, Hispanic ancestry, EOI MRD were no longer negative prognostic factors. Re: genetic risks... (1/2) #ASH25

Ruth Wang'ondu from @stjuderesearch.bsky.social presents on pediatric pts w/ NCI-SR ALL at dx (age 1-<10, WBC <50k/mcL) receiving 3-drug induction on AALL0932 -> reclassified as NCI-HR/VHR based on pathologic/MRD findings (could be enrolled on AALL1131 -> aBFM backbone w/ randomizations. 1/2 #ASH25

Amanda DiNofia @childrensphila.bsky.social presents on tisa-cel for 1st CNS relapse in pediatric B-ALL (group that did NOT benefit from blina in AALL1331). 43 pts w/ CNS relapse (age 0-29, 1st in 39/43) w/o cXRT for relapse rec'd tisa-cel. At d28, 41/42 evaluable pts in CNS remission. (1/2) #ASH25

Dr. Ying Wang presents updated Ph1b/2 study data w/ MK-1045 (humanized bispecific IgG4 CD19xCD3 T-cell engager) in R/R B-ALL. Long-half life allows weekly IV admin (not IVCI). 75 pts treated, 10 dose levels; 73 efficacy-evaluable. CR/CRi/CRh in 55% (83% w/ dose ≥60mg). 9 w/ (1/2) #ASH25 prior blina

Dr. Lucy Cain of @childrensphila.bsky.social presents on humanized CD19-targeted CAR T-cell product (huCART19) for R/R B-ALL (HR and post-CAR relapse): 100 pts age 0-29 treated (52 CAR naive, 48 CAR exposed). Majority pts had MRD or less at tx. 94%/77% CR/Cri d28 (CAR naive/exposed). (1/2) #ASH25

Marlise Luskin from @danafarber.bsky.social presents on inotuzumab/venetoclax (ino/ven) in R/R B-ALL/LBL -> induction w/ 1-2 28d cycles of ven added to ino. If CR, consolidation w/ 21d ven + ino for up to 6 cycles. Dex given prephase + w/ induction. 23 pts enrolled (4 Ph+), no DLTs. (1/2) #ASH25

Gowrishankar Palaniswamy presents on EfficientNetB1, an AI application reviewing blood smears/marrow (BM) studies in pts w/ ALL. Goal to distinguish benign lymphocytes from ALL and assign early pre-B, pre-B, and pro-B classification. Highly reproducible without loss over epochs. (1/2) #ASH25

Nicholas Short of @mdanderson.bsky.social presents paired analysis of NGS for IgH/TCR and PCR for BCR::ABL1 in 80 adults w/ Ph+ ALL w/ clonoSEQ MRD neg. Strong correlation between FISH+ in segmented nuclei at dx and PCR+/NGS- state later. NGS-/PCR- vs NGS-/PCR+ w/ similar OS/relapse. (1/2) #ASH25

Rohaum Hamidi of @stanfordmedicine.bsky.social presents study of clonoSEQ to measure disease burden and B-cell load prior to LD chemo and CAR T-cell therapy. 60 pts age 1-26 treated w/ CD19, CD22, or dual CD19/22 CAR T-cells at Stanford. Peak sequence abundance assoc w/ better EFS/OS. (1/2) #ASH25

Dr. Roberta Azevedo of @mdanderson.bsky.social presents on predictors of relapse post-blina/inotuzumab (ino) w/ or w/o alloHCT: 203 adults in first salvage. 65 pts received blina/ino, 71 received ino alone, 36 received BLIN alone, 117 received chemo w/ ino or BLIN ->172/203 CR. (1/2) #ASH25

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#ASH25 #bmtsm Jiang: no role for FLT3i maintenance in pts MRD neg at d30 who don’t have high risk factors (ELN22 adv, relapse, MRD pos pre-HCt), but in high risk pts there was benefit for maintenance even if d30 MRD neg. FLT3i used for at least one year.

Matthew Wieduwilt presents follow-up data from Alliance (A041703) study for adults ≥60y w/ Ph-neg B-ALL. Single agent ino x1-2 cycles adapted to response ->3-4 cycles of blina. Summary of other frontline inotuzumab (ino)-based regimens below. 33 patients (median age 71, range 60-84). (1/2) #ASh25

Ibrahim Aldoss of @cityofhope.bsky.social presents study of 18 pts age 55 and up w B-ALL in CR1 following any initial therapy (w/o immediate plan for HCT) treated w/ single dose of 4-1BB CD19-targeted CAR T-cells as consolidation. No DLT in safety lead-in (n=6); 12 add'l pts enrolled. (1/2) #ASH25

Dr. Runxia Gu presents data from a phase 2 study from China utilizing CAR T-cells as 1L consolidation for Ph+ ALL. Schema: overembatinib, vincristine, pred and venetoclax as induction -> 1-2 cycles of TKI + pred/ven consolidation -> 4-1BB CD19-targeted CAR-T-> ven/TKI + POMP maintenance (1/2) #ASH25

@anand-88-patel.bsky.social from Univ of Chicago presents on a TKI + inotuzumab (ino) combinations for new dx Ph+. 1° endpoint: MR3 after 2 courses of therapy. Scheme 1: DAS , dex, ino -> TKI + POMP; change DAS to PON if no Mr4 after C2. Some VOD seen -> Scheme 2: Lower dose/less ino. #ASH25 (1/2)

Yosr Hicheri presents EWALL-PH03 study of imatinib (IMA) vs ponatinib (PON) w/ low-intensity chemo in pts ≥55y with newly diagnosed Ph+ ALL; 3rd arm of PON/blina stooped for financial reasons. 1° endpoint: MR4 after consolidation; 2°: EFS. More HTN in PON arm. No CNS relapses ((1/2) #ASH25

Dr. Chiaretti of GIMEMA presents results of RCT of ponatinib + blina (vs imatinib + chemo), 2:1 randomization, 236 enrolled, around 30% IKZF1-plus. Higher rates of molecular response (71% vs 49%) w/ pon/blina. Reduced utilization of transplant noted vs D-ALBA. (1/2) #ASH25

Petri Polonen of @stjuderesearch.bsky.social discusses "TALLForest," an automated multi-omic classifier. Group has previously distinguished T-ALL subtypes using RNAseq and here used gene expression and WGS data from large RCT (AALL0434) from pts age 1-29 w/ T-ALL/LBL. (1/2) #ASH25

Carol Fries from @urochester.bsky.social presents on IgH clonal diversity in B-ALL; diverse V-DJ subclones (20% of pts) are often non-trackable + distinct clones may respond differently to tx. scRNQseq + CYTOF in pt samples showed V-DJ rearr. state uncoupled from cell development state.(1/2) #ASH25

Jason Xu (@stjuderesearch.bsky.social) reports on impact of VNTR in TPMT promoter region (beyond coding variants in TPMT). Hypothesis: ↑ VNTR repeats associated w/ ↓ enzymatic activity of TPMT & ↑myelosuppression 2/2 thiopurines. Genotype pipeline below. Allele types vary w/ ancestry. (1/2) #ASH25

Michael Andreeff from @mdanderson.bsky.social presents on generaing iPS-derived MSCs secreting IL7/15. MSCs heteroeneous -> iMSC less heterogeneous; retain differentiation capacity, better proliferation. IL-7 may promote T-cell survival and IL-15 may enhance proliferation and cytotox. (1/2) #ASH25

Ilio Leontari from Imperial College London presents on one potential approach to address leptomeningeal disease (LMD) in ALL and MM -> iNKT cells (invariant TCR recognises lipid antigens presented by CD1d, MHC class I-like glycoprotein) have higher higher expression of ITGA4/ITGB1. (1/2) #ASH25

Dr. Rizman Romee presents on cytokine-induced memory-like (CIIML) NK cells in combination w/ BHV-1100, an antibody recruiting molecule (ARM) -> binds CD38 on MM and CD16 (via IgG) on NK cells -> enhances NK activation, CIML activity in animal model w/o NK fratricide. Ph 1 trial done (1/2) #ASH25

Dr. Andrew McIntyre from Univ of Oxford presents on biological outcomes of prophylactic transfer of CD4+ T-cells post alemtuzumab-based, RIC matched related donor HCT for heme malignancy -> increase in CD4+ TFH population + marked reduction in CD8+ effector cell accumulation. (1/2) #ASH25 #BMTsm

Ho Ngai from @mdanderson.bsky.social: identified expanded, polyclonal T-cell responses vs 29 known/novel neoantigen peptide::HLA complexes in myeloid dz-> TCR T-cells generated/tested -> TCR-T to DNMT3A:R882H on HLAA*01:01 or IDH2:R140Q on HLA-B*07:02 -> selective killing of 1° human AML. #ASH25

#ASH25 (Abs 47): Encouraging early results (N=21, median age 70 y) from ph2 SAVE trial of all-oral regimen: revumenib + decitabine/cedazuridine + venetoclax in ND NPM1- or KMT2A-mutated AML. 86% ORR, 81% CR/CRh. #Medsky #cansky #oncsky #AML www.cancercommunicator.com/oral-menin-b...

Alberto Peloso (Univ of Padua) presents on myelomonocytic lineage (mm-SW) in B-ALL using single cell analysis. At dx, early differentiation block. Monocyte-like profile at day 15 w/ evidence of transcriptional reprogramming incl distinct patterns by DNA methylation profiling. (1/2) #leusm #ASH25

Dr. Mehta of @childrensphila.bsky.social presents on selection of myeloid subclones following chemo for HR B-ALL (KMT2Ar, Ph-like, Ph+, iAMP21). Comprehensive profiling on samples at dx & end-induction MRD included scRNA-seq, scATAC-seq, scDNA-seq, CITE-seq, spectral flow (1/2) #ASH25

Siyuan Liu discusses the rare, ultra-high risk subtype of TCF3::HLF B-ALL. 34 cases in series. Most w/ CD13 and/or CD33 expression. Transcriptomic overlap between isoforms noted. Isolated RAS pathway mutations in majority of cases. Blina/CAR T-cells effective in achieving MRD-neg state (1/2) #ASH25

Benjamin Simpson (Autolus) presents data from pivotal FELIX trial (R/R B-ALL) correlating drug product (DP) and leukapheresis product (LP) T-cell phenotypes w/ outcomes. Greater % Tcm in DP assoc w/ better OS; poor correlation between LP and DP phenotypes noted. #ASH25 #leusm

#SCOTUS denies a stay of execution to Alabama death-row prisoner Anthony Boyd, over *quite* a dissent from the three Democratic appointees, written by Justice Sotomayor, about the problems with nitrogen hypoxia as a method of execution: www.supremecourt.gov/opinions/25p...

Co-discoverer of reverse transcriptase at 32, Nobel Prize at 37, played a key role at the 1975 Asilomar comference.

Carlo Acutis will likely be the first saint with Pokémon mentioned in his bio; I'd like to think he'd share my enthusiasm for Quaxly. Beyond the hype of being a patron saint of gamers, however, I find it more compelling that he lived in our context and reminds us of God's presence in all things. 1/2

Results of a pilot study led by investigators at @mskcancercenter.bsky.social showed that interleukin-18 “armored” CAR T cells targeting CD371 were effective at treating relapsed/refractory acute myeloid #leukemia at low doses. @markgeyermd.bsky.social Learn more: bit.ly/4mFwo9q