Flow MRD pre-blinatumomab consolidation, despite subsequent clearance, is associated with inferior survival in Ph+ B-ALL

Although adults with Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (B-ALL) may achieve a measurable residual disease-negative (MRD-) complete response (CR) after frontline treatment and blinatumomab (blina) consolidation, survival outcomes are heterogeneous, and known prognostic factors are limited. We conducted a retrospective, multicenter study of 81 adults with Ph+ B-ALL in MRD- (<10-4) CR1 after blina consolidation and stratified them by pre-blina MRD status as determined by multiparametric flow cytometry (flow). Patients who were pre-blina flow MRD- (n = 56) and flow MRD+ (n = 25) had similar baseline characteristics. With a median follow-up of 31.0 months, pre-blina flow MRD- patients had superior disease-free (DFS) and overall survival (OS) on univariate (p = 0.049 and p = 0.045, respectively) and multivariable analyses (HR 0.27, 95% CI 0.08-0.87 and HR 0.17, 95% CI 0.03-0.90, respectively) relative to pre-blina flow MRD+ patients. Inferior DFS was seen with the IKZF1-plus genotype (HR 3.51, 95% CI 1.08-11.44) and extramedullary disease at diagnosis (HR 3.90, 95% CI 1.19-12.73). In exploratory analyses, pre-blina flow MRD+ status remained associated with inferior DFS (p = 0.0005) and OS (p < 0.0001) for patients who did not receive a subsequent hematopoietic cell transplant (HCT) in CR1, but not in patients who did (p = 0.55 and p = 0.99, respectively). In summary, flow MRD+ status before blina consolidation was associated with inferior survival in patients with Ph+ B-ALL in CR1 despite subsequent clearance, and consolidative HCT may reduce this prognostic effect.

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Journal
Blood Advances
Published
2026-10-15
DOI
https://doi.org/10.1182/bloodadvances.2026020724
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
0.00

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article

Flow MRD pre-blinatumomab consolidation, despite subsequent clearance, is associated with inferior survival in Ph+ B-ALL

Andrew Mark Brunner, Eric S. Winer, Kuo‐Kai Chin, Marlise Rachael Luskin et al.
Blood Advances
Acute Lymphoblastic Leukemia research
article

Flow MRD pre-blinatumomab consolidation, despite subsequent clearance, is associated with inferior survival in Ph+ B-ALL

Andrew Mark Brunner, Eric S. Winer, Kuo‐Kai Chin, Marlise Rachael Luskin, Yael Flamand, Mark Blaine Geyer, Natalia M. Tijaro-Ovalle, Martha Wadleigh, Rupa Narayan, Shai O. Shimony, Evan Chris Chen, Benjamin F. Frost, Eytan M. Stein, Virginia Olivia Volpe, Amir T. Fathi, Richard Maury Stone, Leora S. Boussi, Hanno R. Hock, Andriy Derkach, Daniel J. DeAngelo, Meira Yisraeli Salman, Yannis K. Valtis, Yanming Zhang, Christopher A. Hergott, Jacqueline Suen Garcia, Emilie W. Baxter, Maximilian Stahl, Jae H Park, David Nemirovsky
article en

Abstract

Although adults with Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (B-ALL) may achieve a measurable residual disease-negative (MRD-) complete response (CR) after frontline treatment and blinatumomab (blina) consolidation, survival outcomes are heterogeneous, and known prognostic factors are limited. We conducted a retrospective, multicenter study of 81 adults with Ph+ B-ALL in MRD- (<10-4) CR1 after blina consolidation and stratified them by pre-blina MRD status as determined by multiparametric flow cytometry (flow). Patients who were pre-blina flow MRD- (n = 56) and flow MRD+ (n = 25) had similar baseline characteristics. With a median follow-up of 31.0 months, pre-blina flow MRD- patients had superior disease-free (DFS) and overall survival (OS) on univariate (p = 0.049 and p = 0.045, respectively) and multivariable analyses (HR 0.27, 95% CI 0.08-0.87 and HR 0.17, 95% CI 0.03-0.90, respectively) relative to pre-blina flow MRD+ patients. Inferior DFS was seen with the IKZF1-plus genotype (HR 3.51, 95% CI 1.08-11.44) and extramedullary disease at diagnosis (HR 3.90, 95% CI 1.19-12.73). In exploratory analyses, pre-blina flow MRD+ status remained associated with inferior DFS (p = 0.0005) and OS (p < 0.0001) for patients who did not receive a subsequent hematopoietic cell transplant (HCT) in CR1, but not in patients who did (p = 0.55 and p = 0.99, respectively). In summary, flow MRD+ status before blina consolidation was associated with inferior survival in patients with Ph+ B-ALL in CR1 despite subsequent clearance, and consolidative HCT may reduce this prognostic effect.

Blood Advances
Brigham and Women's Hospital (US), Memorial Sloan Kettering Cancer Center (US), Harvard University (US), Yale Cancer Center (US), Dana-Farber Cancer Institute (US), Mass General Brigham (US)
Conquer Cancer Foundation, Amgen, Pfizer, AstraZeneca, Gilead Sciences, American Society of Clinical Oncology, Celgene, Agios Pharmaceuticals, Incyte, Syndax Pharmaceuticals, Astellas Pharma, Servier, Swedish Orphan Biovitrum, National Institutes of Health, Genentech, Sanofi Genzyme, National Cancer Institute, Daiichi Sankyo Europe
Good health and well-being
Openalex Percentile: Top 10%
Acute Lymphoblastic Leukemia research
DOIOpen Access PDFOpenAlex
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