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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Expansion seen w/in first 14d. Toxicities most commonly hematologic (febrile neutropenia) & infection. G1-2 fevers in 7/20 w/o severe CRS. 50% ORR (39% CR/CRh, all MRD neg). Longest responses >1y. Dose expansion ongoing at 1.5x10^9 million on day 0/7/14. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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.

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Cytopenias common as below w/ improvement on disease clearance. ORR 67% (CR/CRi 64%). Median DOR 9.7 months. Consolidative alloHCT assoc w/ better DOR/OS. TENACITY-01 study in US ongoing. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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)

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

2/11 G3+ CRS, 3/11 ICANS, 10/11 transient rash, G4 hematotox and viremia in all. All had expansion in PB by ddPCR. All CRi; "deep" in 9/11. 7/11 alive in CR after alloHCT. NEJM publication out today (www.nejm.org/doi/full/10....). (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Interestingly, one pt developed donor-derived AML, rapidly progressive. Overall, encouraging that all pts achieved MRD-neg CRi and most were able to be bridged to alloHCT. Peri-transplant shock and disease relapse remain concerns. #ASH25 (2/2)

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

G3 CRS in 10% and 2/30 developed ICANS. All responded in CNS and 22/24 had MRD-neg CR in marrow; lower but strong resp rates for EMD. 18/24 CR pts proceeded to alloHCT consolidation. Encouraging long-term follow-up through small N. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

18% overall w/ G2+ LV systolic dysfunction. No sig benefit w/ ACEi before LV systolic dysfunction but possible protective effect w/ earlier initiation. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Incidence of CNS decreased to 18% and lower incidence of CNS relapse. Inferior relapse w/ CNS3 disease driven at least in part by CNS relapse. AlloHCT also ↓ risk of CNS relapse. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Better outcomes as expected in those achieving CR/CRi or getting to alloHCT. Ven didn't improve OS/EFS either. Remains a challenging pt population to treat; oral decitabine may be attractive for some as well given lack of advantage for aza. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Risk factors (HTN, tobacco, HLD, etc) balanced w/ propensity score matching. 13.1 vs 9.2% HF (6.9 vs 3.5% HFrEF) w/ dauno vs ida. All cause mortality similar. Cardiac-related mortality not assessed. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Relative and absolute BMA blast reduction from baseline to day 14 was not associated significantly w/ CR post-reinduction, or w/ DFS/OS. Reason for pursuing reinduction (or not) isn't available and doesn't compare different strategies. Will be good to compare w/ those not reinduced. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Certain risk factors for BM relapse (age, female sex) did NOT predict CNS relapse. CNS status at dx predictive of CNS but not BM relapse. EOI MRD, unfavorable genetics, specific race/ethnic groups (see linked figure), associated w/ both CNS and BM relapse. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

89% CR; MRD responses as below. 17% rec'd TKI. Non-NUP214::ABL1 had 15% vs 5% rate of induction failure. 5y EFS 78% overall, numerically better w/ NUP214::ABL1. No clear benefit to TKI in non-BCR::ABL1, but small N. alloHCT in CR1 assoc w/ ↑EFS. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

4y EFS 73.4%, MRD dependent (see KM curves) and compared somewhat unfavorably w/ non-PAX5r. FLT3 expression ↑ by RNAseq (vs other subtypes); gilteritinib had activity in vitro and PDX model. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

On multivariable analysis, obesity, WBC >50k/mcL, TP53m, assoc w/ ↑ relapse. Median OS in 1st relapse 7 months w/ 2y OS 30%; advances in salvage therapy such as CAR T-cells may improve outcomes. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

Unfavorable genetics (hypodip, KMT2Ar, iAMP21, TCF3::HLF) still retained prognostic significance but benefitted from blina. Future publication will help address impact of blina even in chemosensitive subtypes. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

AALL1131 tested different IT (HR) or consolidation chemo (VHR). 7y post-induction DFS/OS 85.3/94.1% (excellent) w/ low total anthracycline exposure. Outcomes anticipated to improve even further w/ addition of blina. 2/2 #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 08/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

CR in 100% w/in 2m. 88% avoided cXRT. 1y/2y EFS 90% censoring for alternative tx. Among 14 pts w/ >4y potential follow-up, 4y EFS 71/OS 93%. 4 pts w/ morphologic relapse (1 medullary, 1 combined, 1 CNS2, 1 lineage switch); 2 had MRD-level relapse. 1y/2y OS 100/90%. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

CRS in 45% (3% G3, none G4+). No ICANS seen! Median DOR 11.3 months. Only 5 pts at target dose had received prior blina or CD19-targeted CAR T-cells (5/5 responses). Evaluation of RP2D is ongoing. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

CAR-exposed: 2y EFS/RFS 53%/72%, 4y 50%/68%. CAR-naive: 2y EFS/RFS 65%/70%, 4y 57%/62%. 4y RFS 37% in CAR naive w/ early BM relapse. ICANS in 14/52 (27%, 2 G3, 2 G4) CAR-naïve patients and 7/48 (15%, 1 G3, 1 G4) CAR-exposed, w/ 1 case of G3 cerebral edema, fully recovered. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

Essentially uniform concordance between model and expert assessment. Possibility to use as a point-of-care/decision-support tool? Ability to distinguish specific cytogenetic/molecular subtypes & prognosis by morphology-based AI unclear but of interest. (2/2) #ASH24

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

However, in pts w/ low disease burden (<5% in marrow), higher B-cell load in marrow assoc w/ better EFS. Lower risk of relapse if CAR T-cells given in 1st relapse (vs 2nd or later). #ASH25 (2/2)

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

68% flow MRD neg after 1 cycle. 47% underwent HCT at median 4 mos; 10% rec'd CAR T-cells. Trend to better outcomes in pts age ≤70 w/ HCT. Among pts with early relapse (<12 mos CR1) and/or MRD positivity, alloHCT assoc w/ improved outcome. Future use of CAR T-cell consol of interest. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

3-year EFS 48%/OS 59%, median EFS 31 months. 12 relapses noted ((4 CD19 and/or CD22 neg). MRD+ after course 1A highly predictive of EFS but small #s. Comparable 3y EFS/OS/CIR to other ino-containing regimens. Unclear currently if chemo adds value to ino/blina in older pts w/ B-ALL. (2/2) #ASH25

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

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

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Mark Geyer, M.D. @markgeyermd.bsky.social · 07/12/2025

Expansion seen even w/ MRD negativity at infusion. 13/18 G1 CRS (no ICANS or G2+ CRS). w/ median follow up 14.5 months, 1-yr EFS 94%/OS 100%. Only 1 pt (Ph+) w/ molecular relapse (negative FC) at 6 months while on TKI maintenance -> TKI change -> consolidative HCT. One lineage switch. (2/2) #ASH25

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