Mark Geyer, M.D.

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

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.

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

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)

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

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

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)

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

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

*2 weeks median

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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