Immunotherapy refractoriness and early post-alloHCT relapse define ultra-high-risk B-ALL after CD19 CAR T-cell therapy

Authors

• Valentín Ortiz-Maldonado
• Jacques-Emmanuel Galimard
• Giorgio Ottaviano
• Anna Alonso-Saladrigues
• Shatha Farhan, Henry Ford HealthFollow
• Sowjanya Vuyyala
• Eva Michel
• Fizza Imran
• Nazaret Sánchez-Sierra
• Nuria Martínez-Cibrian
• Samppa Johannes Ryhänen
• Richard Mitchell
• Stephan Mielke
• Soeren Lykke Petersen
• Anne-Charlotte Teyssier
• Thomas Pabst
• Jürgen Kuball
• Pere Barba
• Antonio Pérez-Martínez
• Andishe Attarbaschi
• Arnon Nagler
• José Antonio Pérez-Simón
• Malte von Bonin
• Emma K Nicholson
• David Beauvais
• Federica Sorà
• Muriel Paganessi
• Olaf Penack
• Cristina Castilla-Llorente
• Yves Beguin
• Julio Delgado
• Susana Rives
• Krzysztof Kalwak
• Fabio Ciceri
• Annalisa Ruggeri
• Adriana Cristina Balduzzi
• Sebastian Giebel

Recommended Citation

Ortiz-Maldonado V, Galimard JE, Ottaviano G, Alonso-Saladrigues A, Farhan S, Vuyyala S, Michel E, Imran F, Sánchez-Sierra N, Martínez-Cibrian N, Ryhänen SJ, Mitchell R, Mielke S, Petersen SM, Teyssier AC, Pabst T, Kuball J, Barba P, Pérez-Martínez A, Attarbaschi A, Nagler A, Pérez-Simón JA, von Bonin M, Nicholson EK, Beauvais D, Sorà F, Paganessi M, Penack O, Castilla-Llorente C, Beguin Y, Delgado J, Rives S, Kalwak K, Ciceri F, Ruggeri A, Balduzzi AC, Giebel S. Immunotherapy Refractoriness and Early Post-AlloHCT Relapse Define Ultra-High-Risk B-ALL after CD19 CAR T-Cell Therapy. Blood Adv. 2026.

Document Type

Article

Publication Date

9-30-2026

Publication Title

Blood Adv

Abstract

CD19-directed CAR T-cell therapy (CART19) has transformed relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) management, but the prognostic impact of immunotherapy sensitivity and post-allogeneic hematopoietic cell transplantation (alloHCT) relapse timing in real-world practice remains unclear. We retrospectively analyzed EBMT registry patients with R/R B-ALL treated with CART19 (2016-2023), stratifying by prior alloHCT and classifying prior blinatumomab and inotuzumab ozogamicin (InO) as naïve, responder (CR/CRi), or refractory. Among 345 patients (173/172 adults/children), median age was 18 years (range 1.1-78.2); 58% were alloHCT-exposed, 27% blinatumomab-exposed, 29% InO-exposed, and 52% had pre-lymphodepletion morphological disease. With a median follow-up of 2.3 years, the 3-month MRD-negative complete remission cumulative incidence was 78%; 2-year overall survival (OS) and event-free survival (EFS) were 65% and 49%. In alloHCT-naïve patients, 2-year OS/EFS were 83%/60% (blinatumomab responders), 65%/55% (blinatumomab-naïve), and 31%/17% (blinatumomab-refractory); for InO, OS/EFS were 68%/54% (naïve), 62%/55% (responders), and 22%/18% (refractory). In alloHCT-exposed patients, blinatumomab category did not discriminate outcomes, whereas InO refractoriness was associated with inferior OS/EFS (49%/29%) versus InO-naïve (71%/54%) and responders (60%/38%). Early relapse after alloHCT (< 6 vs ≥6 months) was associated with worse 2-year OS (43% vs 74%) and EFS (31% vs 54%). In multivariable models, immunotherapy refractoriness independently predicted inferior EFS (HR 2.56 in alloHCT-naïve; HR 2.20 in alloHCT-exposed); overt morphological disease at lymphodepletion in alloHCT-naïve (HR 3.34) and early post-alloHCT relapse (HR 1.85) further worsened EFS. These findings support pragmatic pre-CAR T risk stratification and prioritization of trials or intensified strategies for refractory disease and early post-alloHCT relapse.

PubMed ID

42815156

ePublication

ePub ahead of print