<i>TP53</i> mutations are associated with CD19− relapse and inferior outcomes after blinatumomab in adults with ALL

Despite the success of the CD19 × CD3 T-cell engager blinatumomab in B-cell acute lymphoblastic leukemia (B-ALL), treatment failure is common and can manifest with antigen loss and extramedullary disease (EMD) relapse. To understand the impact of leukemia genetics on outcomes, we reviewed 267 adult patients with B-ALL treated with blinatumomab and used next-generation sequencing to identify molecular alterations. Patients received blinatumomab for relapsed/refractory (R/R) disease (n = 150) and minimal residual disease (MRD; n = 88), upfront as induction (n = 10) or as consolidation in MRD-negative state (n = 19). In the overall cohort, 50 patients (19%) had Philadelphia chromosome (Ph)-positive ALL, 80 (30%) had Ph-like ALL, 35 (13%) had TP53 mutations (TP53m), 7 (3%) had KMT2A rearrangement, and 8 (3%) had PAX5 alterations. For patients treated for R/R ALL, the overall complete remission (CR)/CR with incomplete hematological recovery (CRi) rate was 59%. Only pretreatment high disease burden (P < .01) and active EMD (P < .01) were associated with inferior CR/CRi rate. Of 169 patients in CR/CRi after blinatumomab, 79 (47%) patients relapsed, including 22 (28%) with CD19- and 54 (68%) with CD19+ relapse. In multivariable analysis, TP53m was associated with an increased risk of CD19- relapse (hazard ratio [HR], 6.84; 95% confidence interval [CI], 2.68-17.45; P < .01). Post-blinatumomab allogeneic stem cell transplantation consolidation was associated with a lower risk of CD19- relapse (HR, 0.10; 95% CI, 0.03-0.37; P < .01) and EMD relapse (HR, 0.36; 95% CI, 0.18-0.73; P < .01). In conclusion, leukemia genetics may predict patterns of blinatumomab failure, with TP53m associated with CD19- relapse.

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Publication Details

Journal
Blood Advances
Published
2025-01-16
DOI
https://doi.org/10.1182/bloodadvances.2024014986
Citations
10
Primary Topic
Chronic Myeloid Leukemia Treatments
Type
article
Field-Weighted Citation Impact
17.70

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article

TP53 mutations are associated with CD19− relapse and inferior outcomes after blinatumomab in adults with ALL

Lindsey Murphy, Zhaohui Gu, Vaibhav Agrawal, Anthony S. Stein et al.
10 citations
Blood Advances
Chronic Myeloid Leukemia Treatments
17.70
article

TP53 mutations are associated with CD19− relapse and inferior outcomes after blinatumomab in adults with ALL

Lindsey Murphy, Zhaohui Gu, Vaibhav Agrawal, Anthony S. Stein, Vinod A. Pullarkat, Mary C. Clark, Amanda Blackmon, Jose Tinajero, Ahmed Aribi, Ibrahim Taha Aldoss, Dat Ngo, Monzr M. Al Malki, Pamela S. Becker, Shukaib Arslan, Andrew Artz, Brian Ball, Guido Marcucci, Karamjeet Sandhu, Amandeep Salhotra, Paul Koller, Haris Ali, Michelle Afkhami, Hoda Pourhassan, Salman Otoukesh, Idoroenyi Amanam, Ryotaro Nakamura, Jianying Zhang, Shanpeng Li, Stephen J. Forman, Tibor Kovacsovics
article en
10 citations

Abstract

Despite the success of the CD19 × CD3 T-cell engager blinatumomab in B-cell acute lymphoblastic leukemia (B-ALL), treatment failure is common and can manifest with antigen loss and extramedullary disease (EMD) relapse. To understand the impact of leukemia genetics on outcomes, we reviewed 267 adult patients with B-ALL treated with blinatumomab and used next-generation sequencing to identify molecular alterations. Patients received blinatumomab for relapsed/refractory (R/R) disease (n = 150) and minimal residual disease (MRD; n = 88), upfront as induction (n = 10) or as consolidation in MRD-negative state (n = 19). In the overall cohort, 50 patients (19%) had Philadelphia chromosome (Ph)-positive ALL, 80 (30%) had Ph-like ALL, 35 (13%) had TP53 mutations (TP53m), 7 (3%) had KMT2A rearrangement, and 8 (3%) had PAX5 alterations. For patients treated for R/R ALL, the overall complete remission (CR)/CR with incomplete hematological recovery (CRi) rate was 59%. Only pretreatment high disease burden (P < .01) and active EMD (P < .01) were associated with inferior CR/CRi rate. Of 169 patients in CR/CRi after blinatumomab, 79 (47%) patients relapsed, including 22 (28%) with CD19- and 54 (68%) with CD19+ relapse. In multivariable analysis, TP53m was associated with an increased risk of CD19- relapse (hazard ratio [HR], 6.84; 95% confidence interval [CI], 2.68-17.45; P < .01). Post-blinatumomab allogeneic stem cell transplantation consolidation was associated with a lower risk of CD19- relapse (HR, 0.10; 95% CI, 0.03-0.37; P < .01) and EMD relapse (HR, 0.36; 95% CI, 0.18-0.73; P < .01). In conclusion, leukemia genetics may predict patterns of blinatumomab failure, with TP53m associated with CD19- relapse.

Blood AdvancesVol. 9(9)
City Of Hope National Medical Center (US), City of Hope (US), Goodyear (United States) (US), Beckman Research Institute
National Institutes of Health, National Cancer Institute
Openalex Percentile: Top 1%
Chronic Myeloid Leukemia Treatments
17.70
DOIOpen Access PDFOpenAlex
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